Source	Date	Reviewed	Tier	Biomarker	Alteration	Cancer type	Therapies	Comments	Evidence
GIMR	2020-05-21	FL	1	ABL1	BCR-ABL1 Fusion	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Dasatinib	PBS reimbursed. Second or third-line agent. Requires presence of the BCR-ABL transcript in either peripheral blood or bone marrow.	20525995
GIMR	2020-05-21	FL	1	ABL1	BCR-ABL1 Fusion	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Imatinib	PBS reimbursed. First-line treatment. Requires presence of the BCR-ABL transcript.	12637609
GIMR	2020-05-21	FL	1	ABL1	BCR-ABL1 Fusion	Chronic myelogenous leukaemia	Nilotinib	PBS reimbursed. Second or third-line agent. Requires cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1%	20525993
GIMR	2020-12-09	FL	1	ABL1	BCR-ABL1 Fusion and T315I	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Ponatinib	PBS reimbursed for acquired T315I mutation. Fourth line treatment. Requires cytogenetic evidence of the Philadelphia chromosome, or RT-PCR level of BCR-ABL transcript greater than 0.1%. PACE2	23190221, 24180494
GIMR	2020-04-16	FL	1	ALK	EML4-ALK Fusion, Fusions	Non-small cell lung cancer	Alectinib	PBS reimbursed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. In first-line setting, alectinib had a superior 12 months EFS of 68% vs crizotinib 49% (ALEX trial). In J-ALEX trial, the median PFS was NR (alectinib) vs 10.2 months (crizotinib).	28586279, 28501140
GIMR	2020-04-16	FL	1	ALK	EML4-ALK Fusion, Fusions	Non-small cell lung cancer	Ceritinib	PBS reimbursed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. ASCEND-5 – In post-crizotinib and chemotherapy setting, Ceritinib had superior median PFS than 5.4 v docetaxel 1.6 months. ASCEND-4 – In first-line setting, Ceritinib has superior PFS 16.6 vs platinum chemotherapy 8.1 months.	24670165, 28126333, 28602779
GIMR	2020-04-16	FL	1	ALK	EML4-ALK Fusion, Fusions	Non-small cell lung cancer	Crizotinib	PBS reimbursed. Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. PROFILE1014 trial – in the first-line setting, Crizotinib had a superior PFS 10.9 vs chemotherapy 7.0 months. In the second-line setting, Crizotinib had longer PFS 7.7 vs docetaxel 3.0 months. No OS difference shown in either trials due to crossover of subgroups.	20979469, 25470694
GIMR	2020-04-16	FL	1	ALK	EML4-ALK Fusion, Fusions 	Non-small cell lung cancer	Brigatinib	TGA approved. PBS reimbursed. FDA approved. Phase 3 ALTA-1L trial. NCT02737501. N=275. Brigatinib demonstrated superior PFS (24.0 vs 11.0 months) and improved health-related quality of life in ALK inhibitor-naive ALK-positive non-small cell lung cancer patients, with consistent results across independent and investigator assessments.	30280657, 32780660
GIMR	2020-04-16	FL	1	ALK	EML4-ALK Fusion, Fusions 	Non-small cell lung cancer	Lorlatinib	PBS reimbursed after progression on ALK inhibitor other than Crizotinib.  Requires fluorescence in situ hybridisation (FISH) testing for ALK gene rearrangement, defined as 15% (or greater) positive cells. In Phase 3 trial vs crizotinib (CROWN): OS was superior at12 months 78% vs 39%	30413378, 33207094, 10.1016/j.annonc.2020.08.2282
GIMR	2020-06-15	FL*	1	BCL2	Overexpression	Chronic lymphocytic leukaemia	Venetoclax	TGA approved for R/R CLL with Chr 17p deletion or  for whom there are no other suitable treatment options.	26639348, 27178240
GIMR	2020-06-15	FL*	1	BCL2	Overexpression	Chronic lymphocytic leukaemia	Venetoclax + Rituximab	TGA approved. Phase 3 trial. NCT02005471. N=389. Venetoclax-rituximab demonstrates significantly improved 2-year progression-free survival (85% vs 36%) compared to bendamustine-rituximab in relapsed or refractory chronic lymphocytic leukemia, with BCL2 overexpression being a characteristic of CLL cells.	29562156
GIMR	2020-05-04	FL	1	BRAF	V600E	Colorectal adenocarcinoma	Encorafenib + Cetuximab	PBS reimbursed. TGA approved. FDA approved. In Phase 3 BEACON CRC, OS for the encorafenib and cetuximab doublet was 8.2 months. The ORR was 26%. 	31566309, 33503393
GIMR	2020-04-16	FL	1	BRAF	V600E	Melanoma	Dabrafenib	PBS reimbursed. However, single-agent not recommended. Median PFS 5.1 months (NCT01227889) vs dacarbazine 2.7 months. Rate of cutaneous SCC 6%.	22735384
GIMR	2020-04-16	FL	1	BRAF	V600E	Melanoma	Vemurafenib	PBS reimbursed. However, single-agent not recommended. BRIM-3 – higher response rate 48% v dacarbazine 5% with superior OS (HR 0.37). Cutaneous SCC 12%.	21639808
GIMR	2020-04-16	FL	1	BRAF	V600E	Non-small cell lung cancer	Dabrafenib + Trametinib	TGA approved. PBS reimbursed. Phase 2 trial. NCT01336634. N=36. Dabrafenib + trametinib showed an ORR of 64% (23/36) with a median follow-up of 15.9 months in previously untreated BRAFV600E-mutant metastatic NSCLC.	28919011
GIMR	2020-05-15	FL	1	BRAF	V600E, V600K	Melanoma	Binimetinib + Encorafenib	TGA approved. PBS reimbursed. Phase 3 COLUMBUS trial. NCT01909453. Median overall survival was significantly longer with encorafenib plus binimetinib (33.6 months) compared to vemurafenib (16.9 months) in patients with BRAF(V600)-mutant melanoma.	30219628, 10.1200/JCO.2021.39.15_suppl.9507
GIMR	2020-04-16	FL	1	BRAF	V600E, V600K	Melanoma	Dabrafenib + Trametinib	PBS reimbursed. COMBI-D – Addition of trametinib to dabrafenib prolonged median PFS at 3 years (44 vs 32%). 	25265492
GIMR	2020-04-16	FL	1	BRAF	V600E, V600K	Melanoma	Vemurafenib + Cobimetinib	PBS reimbursed. CoBRIM – Addition of cobimetinib to vemurafenib prolonged median PFS 9.9 vs 6.2 months.	25265494
GIMR	2020-04-25	FL	1	BRCA1	Oncogenic mutations	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Niraparib	TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.	31562799, 39284381
GIMR	2020-04-27	FL	1	BRCA1	Oncogenic mutations	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib	PBS reimbursed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%). Median PFS was 56.0 months in the olaparib arm versus 13.8 months in the placebo arm.	30345884, 34715071
GIMR	2020-05-05	FL	1	BRCA1	Oncogenic mutations	Prostate cancer	Olaparib	TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).  Olaparib was associated with longer rPFS over control (HR, 0.22) and OS (HR, 0.63). rPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16).	32343890, 32955174
GIMR	2021-04-07	FL	1	BRCA1	Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib	TGA approved. PBS reimbursed. Phase 3 SOLO2/ENGOT-Ov21 trial. NCT01874353. N=295. Olaparib maintenance therapy significantly improved PFS (19.1 vs 5.5 months) and provided a clinically meaningful OS benefit (51.7 vs 38.8 months) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation.	28754483, 33743851
GIMR	2020-05-31	FL	1	BRCA1	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib + Bevacizumab	TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX.	31851799
GIMR	2020-04-25	FL	1	BRCA2	Oncogenic mutations	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Niraparib	TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012. In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.	31562799, 39284381
GIMR	2020-04-27	FL	1	BRCA2	Oncogenic mutations	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib	PBS reimbursed. Requires identification of class 4 or 5 mutation (germline and somatic). SOLO1 trial - after initial platinum response, maintenance olaparib therapy prolonged PFS at 3 years (60% vs placebo 27%)	30345884
GIMR	2020-05-05	FL	1	BRCA2	Oncogenic mutations	Prostate cancer	Olaparib	TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).  Olaparib was associated with longer rPFS over control (HR, 0.22) and OS (HR, 0.63). rPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16).	32343890, 32955174
GIMR	2021-04-07	FL	1	BRCA2	Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib	TGA approved. PBS reimbursed. Phase 3 SOLO2/ENGOT-Ov21 trial. NCT01874353. N=295. Olaparib maintenance therapy significantly improved PFS (19.1 vs 5.5 months) and provided a clinically meaningful OS benefit (51.7 vs 38.8 months) in patients with platinum-sensitive relapsed ovarian cancer and a BRCA1/2 mutation.	28754483, 33743851
GIMR	2020-05-31	FL	1	BRCA2	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib + Bevacizumab	TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX.	31851799
GIMR	2020-06-15	FL	1	CD19	Protein expression	Acute lymphoblastic leukaemia	Blinatumomab	Phase 3 trial. TOWER. NCT02013167. N=405. Blinatumomab significantly improved overall survival (7.7 vs 4.0 months), remission rates (44% vs 25%), and event-free survival (31% vs 12%) in adults with relapsed or refractory B-cell precursor ALL, including both Ph-positive and Ph-negative subtypes. Note that surface antigen CD-19 is lineage-specific to B-cells and constitutively expressed on the majority of B-cell precursor ALL blasts and does not represent a biomarker selection criteria.	28249141
GIMR	2020-06-15	FL	1	CD20	Protein expression	Follicular lymphoma	Obinutuzumab	Phase 3 trial. TOWER. NCT02013167. N=405. Blinatumomab significantly improved overall survival (7.7 vs 4.0 months), remission rates (44% vs 25%), and event-free survival (31% vs 12%) in adults with relapsed or refractory B-cell precursor ALL, including both Ph-positive and Ph-negative subtypes. Note that surface antigen CD-19 is lineage-specific to B-cells and constitutively expressed on the majority of B-cell precursor ALL blasts and does not represent a biomarker selection criteria.	28976863
GIMR	2020-06-15	FL	1	CD20	Protein expression	Mantle cell lymphoma	Ibrutinib	PBS reimbursed. Phase 2 study. NCT01236391. N=111. Ibrutinib showed a 68% overall response rate (21% complete response, 47% partial response) in patients with relapsed or refractory mantle-cell lymphoma, with median response duration of 17.5 months, median progression-free survival of 13.9 months, and 58% overall survival at 18 months.	23782157, 23782157
GIMR	2020-04-16	FL	1	CD20	Protein expression	Non-Hodgkin’s lymphoma; Chronic lymphocytic leukaemia; Acute lymphoblastic leukaemia; Hodgkin’s lymphoma	Rituximab	PBS reimbursed. References non-exhaustive.	11807147, 20888994
GIMR	2021-09-19	FL	1	CD274	Protein expression	Cervical cancer	Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab; Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab; Pembrolizumab + Cisplatin + Paclitaxel; Pembrolizumab + Carboplatin + Paclitaxel	TGA approved. FDA approval for PD-L1-positive (CPS >=1) first-line treatment of cervical cancer (2021-10-13). KEYNOTE-826. N=548 patients with a PD-L1 CPS >= 1. Median PFS was 10.4 months (pembrolizumab) vs 8.2 months (placebo). OS at 24 months: 53% (pembrolizumab) vs 42% (placebo). No difference in PFS or OS was seen vs chemotherapy in the PD-L1 CPS <1 subgroup. Final analysis showed that the HR of OS results was significantly different in subgroups with or without bevacizumab: 77.1 months (pembrolizumab) versus 61.4 months (control) with bevacizumab, and 53.1 months (pembrolizumab) versus 33.7 months (control) without bevacizumab.	34534429, 39393777
GIMR	2020-09-29	FL	1	CD274	Protein expression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Nivolumab + FOLFOX; Nivolumab + CAPOX	TGA approved. FDA approved. Checkmate-649: Phase 3. First-line, HER2-negative gastric/GOJ carcinoma. Nivolumab plus chemotherapy improved PFS (7.7 vs 6.1 months) and OS (14.4 vs 11.1) over chemotherapy alone in PD-L1 CPS ≥ 5, as well as in CPS>= 1 (PFS: 7.5 vs 6.9 months) and (OS: 14.0 vs 11.3 months). No PFS or OS difference in PD-L1 CPS <5 or CPS <1 subgroups.	34102137, 10.1016/j.annonc.2020.08.2296, 10.1016/annonc/annonc741
POTTR	2020-04-16	FL	1	CD274	Protein expression	Head and neck squamous cell carcinoma 	Pembrolizumab	TGA approved. Not PBS reimbursed. Approved for CPS >= 1; PBS-subsidised if the PD-L1 CPS >= 20 in the tumour sample.	31679945
GIMR	2020-04-25	FL	1	CD274	Protein expression	Non-small cell lung cancer	Pembrolizumab	PBS reimbursed. TGA approved as monotherapy for the first-line treatment of patients with NSCLC expressing PD-L1, and EGFR and ALK negative. Defined as tumour proportion score (TPS) greater than or equal to 1%. KEYNOTE 042 and KEYNOTE-024. 	27718847, 30955977
GIMR	2020-04-25	FL	1	CD274	Protein expression	Non-small cell lung cancer	Pembrolizumab	PBS reimbursed. TGA approved as monotherapy for the subsequent-line treatment of patients with NSCLC expressing PD-L1 (defined as tumour proportion score (TPS) greater than or equal to 1%), and EGFR and ALK negative. KEYNOTE-010	26712084
GIMR	2020-05-30	FL	1	CD274	Protein expression	Triple-negative breast cancer	Pembrolizumab + Nab-paclitaxel; Pembrolizumab + Paclitaxel; Pembrolizumab + Carboplatin + Gemcitabine	TGA approved. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo. Median OS was significantly longer in pembrolizumab plus chemotherapy group (23.0 months) versus chemotherapy alone (16.1 months).	33278935, 35857659, 10.1200/JCO.2020.38.15_suppl.1000
GIMR	2020-04-25	FL	1	CD274	Protein expression	Urothelial carcinoma	Pembrolizumab	PBS listed for cisplatin-ineligible urothelial carcinoma with tumours express PD-L1, defined as Combined Positive Score (CPS) >= 10%. TGA approved. In KEYNOTE-052, positive PD-L1 IHC was determined by CPS with 22C3 pharmDx assay. ORR was 24% (38% in CPS >= 10%). Note: pembrolizumab is TGA approved (but not PBS listed) for treatment of advanced urothelial carcinoma after failure of platinum-based chemotherapy. However, this indication is not biomarker-selected. In KEYNOTE-045, pembrolizumab as second-line monotherapy yielded significantly longer OS than chemotherapy (where higher OS benefit vs chemotherapy was seen in subgroups with both CPS >=1% and >= 10%).	28967485
GIMR	2020-12-11	FL	1	CD274+EGFR+ALK	CD274:Protein expression and NOT EGFR:Oncogenic mutations and NOT ALK:fusion	Non-small cell lung cancer	Atezolizumab	TGA approved. PBS reimbused. Phase 3 IMpower110 trial (NCT02409342, N=572) evaluated first-line atezolizumab in EGFR and ALK negative NSCLC patients with PD-L1 expression ≥1% on tumor cells or tumor-infiltrating immune cells covering ≥1% of tumor area. Atezolizumab significantly improved median OS compared to chemotherapy (20.2 vs 13.1 months, improvement of 7.1 months).	32997907, 10.1093/annonc/mdz293
GIMR	2020-06-15	FL	1	CD38	Overexpression	Multiple myeloma	Daratumumab + Bortezomib + Dexamethasone	Phase 3 trial. NCT02136134. N=498. Daratumumab + bortezomib + dexamethasone significantly improved PFS (HR, 0.39) and ORR (82.9% vs 63.2%) compared to bortezomib + dexamethasone in relapsed or refractory multiple myeloma, with higher CD38 expression associated with better response.	27557302, 27307294
GIMR	2020-04-16	FL	1	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Afatinib	PBS reimbursed, In the first-line setting, median PFS was 11.0 vs 5.6 months for chemotherapy (LUX-Lung 6, Asian patients), 11.1 vs 6.9 months (chemotherapy, LUX-Lung 3) and afatinib has significant TTF and PFS improvement over gefitinib. LUX-Lung 7). ORR was 61% in the second-line setting  (LUX-Lung 2).	22452895, 23816960, 24439929, 27083334
GIMR	2020-04-16	FL	1	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Erlotinib	PBS reimbursed, OPTIMAL	16014882, 16014883
GIMR	2020-04-16	FL	1	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Gefitinib	PBS reimbursed. Phase 3 trials. NCT00322452 and C000000376. Gefitinib significantly improved PFS (10.8 vs 5.4 months, HR 0.30) and ORR (73.7% vs 30.7%) compared to carboplatin-paclitaxel in patients with advanced NSCLC with sensitising EGFR mutations.	15118125, 19692680, 20573926
GIMR	2020-04-16	FL	1	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Osimertinib	PBS reimbursed, FLAURA: osimertinib had median DOR 17.2 months versus standard EGFR TKIs of 8.5 months.	29151359
GIMR	2020-04-16	FL	1	EGFR	Exon 19 deletion, L858R, Exon 21 mutation, T790M	Non-small cell lung cancer	Osimertinib	PBS reimbursed. AURA3: In second-line setting, osimertinib was found to have significantly longer PFS 10.1 vs platinum chemotherapy 4.4 months. 	27959700
GIMR	2021-05-22	FL	1	EGFR	Exon 20 insertion	Non-small cell lung cancer	Amivantamab	TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Median PFS 8.3 months. "Phase 1 CHRYSALIS trial. N=81. Amivantamab, an EGFR-MET bispecific antibody, showed an ORR of 40% (3 complete responses) and median DOR of 11.1 months in patients with EGFR Exon20ins NSCLC progressing on platinum chemotherapy, with a median PFS of 8.3 months.	34339292, 32414908, 10.1200/JCO.2020.38.15_suppl.9512
GIMR	2023-10-29	FL	1	EGFR	Exon 20 insertion	Non-small cell lung cancer	Amivantamab + Carboplatin + Pemetrexed	TGA approved. Not PBS Listed. Not FDA approved. Phase 3 trial. PAPILLON. NCT04538664. N=308. Amivantamab-chemotherapy (carboplatin-pemetrexed) was associated with superior progression-free survival (11.4 months versus 6.7 months) and a higher overall response rate (73% vs 47%) compared to chemotherapy alone in patients with advanced NSCLC with EGFR exon 20 insertions as first line treatment.	37870976
GIMR	2020-04-16	FL	1	EGFR	G719, L861Q, S768I	Non-small cell lung cancer	Afatinib	PBS reimbursed. Phase 3 LUX-Lung 6 trial. NCT01121393. N=364. Afatinib significantly improved PFS (11.0 months vs 5.6 months) compared to gemcitabine and cisplatin in Asian patients with EGFR mutation-positive advanced NSCLC.	24439929
GIMR	2022-07-30	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Docetaxel + Trastuzumab	PBS reimbursed if ISH positive. Trastuzumab + docetaxel significantly improved ORR (61% vs 34%), OS (31.2 vs 22.7 months), and PFS (11.7 vs 6.1 months) over docetaxel alone in HER2-positive metastatic breast cancer patients with manageable additional toxicity.	15911866
GIMR	2020-04-05	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Lapatinib + Capecitabine	PBS reimbursed if ISH positive. HER2-positivity was defined as IHC 3+ or IHC 2+ with FISH amplified in NCT00078572.	17192538
GIMR	2020-04-16	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab	PBS reimbursed if ISH positive. (HER2-positivity was defined as IHC 3+ or FISH amplifed PMID:15800309).	15800309
GIMR	2020-04-16	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab + Capecitabine	PBS reimbursed if ISH positive. (HER2-positivity was defined as IHC 3+ or IHC 2+ with FISH amplified PMID:17679724)	17679724
GIMR	2020-04-16	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab + Paclitaxel	PBS reimbursed if ISH positive. (HER2-positivity was defined as IHC 3+ or FISH amplified. CALGB 9840)	18375893
GIMR	2020-04-16	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab + Pertuzumab + Docetaxel	PBS reimbursed if ISH positive. CLEOPATRA trial: frst-line metastastic disease OS 56.5 (vs 40.8 mo without Pertuzumab).	25693012
GIMR	2020-04-16	FL	1	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab Emtansine	PBS reimbursed if ISH positive. EMILIA (T-DM1 versus lapatinib + capecitabine) and TH3RESA trials (T-DM1 versus physicians choice). HER2-positivity was defined as IHC 3+ or FISH with amplification ratio ≥2.0.	23020162, 24793816, 28526538
GIMR	2021-06-06	FL	1	ERBB2	Amplification, Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Trastuzumab + Capecitabine + Oxaliplatin	TGA approved. PBS reimbursed. Three Phase 2 trials. Ryu et al, HEROX, and CGOG1001. HER2 positivity was defined as IHC 3+ or FISH-positive in all three studies.	25661103, 30927036, 26857702
GIMR	2020-05-15	FL	1	ERBB2	Amplification, Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Trastuzumab + Cisplatin + Fluorouracil; Trastuzumab + Cisplatin + Capecitabine	PBS reimbursed if ISH positive. ToGA trial: First-line treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer. OS: 13.8 vs 11.1 months. (HER2 positivity:  IHC 3+ or FISH: HER2:CEP17 ratio ≥2 in the tral)	20728210
GIMR	2021-06-05	FL	1	ERBB2	Protein expression and NOT Amplification, Low protein expression and NOT Amplification	Breast cancer	Trastuzumab deruxtecan	TGA approved. Phase 3. DESTINY-Breast04. NCT03734029. Compared with physician’s choice, T-DXD prolonged both PFS (10.1 v 5.4 months) and OS (23.9 v 17.5 months) in Hormone receptor-positive, HER2-low metastatic breast cancer. Similarly T-DXD also prolonged PFS (9.9 v 5.1 months) and OS (23.4 vs 16.8 months) compared to physician’s choice in the overall population. HER2-Low was defined as IHC a score of 1+ or 2+ with negative results on in situ hybridization. FDA approved 5/8/2022.	35665782
POTTR	2020-04-16	FL	1	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Abemaciclib + Letrozole; Abemaciclib + Anastrazole	PBS reimbursed. MONARCH-3: abemaciclib yielded significantly longer PFS in HR-positive, HER2-negative metastatic breast cancer.	28968163
POTTR	2020-04-16	FL	1	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Palbociclib + Letrozole	PBS reimbursed. PALOMA-2: palbociclib yielded significantly longer PFS in HR-positive, HER2-negative metastatic breast cancer.	27959613
POTTR	2020-04-16	FL	1	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Ribociclib + Letrozole	PBS reimbursed. MONALEESA-2: ribociclib yielded significantly longer PFS in HR-positive, HER2-negative metastatic breast cancer.	27717303
GIMR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Anastrozole	Restricted benefit: HR-positive metastatic breast cancer.	11745278
GIMR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Exemestane	Restricted benefit: HR-positive metastatic breast cancer.	10735887
POTTR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Fulvestrant	TGA approved. PBS reimbursed. Phase 3 FALCON trial. NCT01602380. N=462. Fulvestrant significantly improved PFS over anastrozole (HR 0.797, 16.6 months vs 13.8 months) in endocrine therapy-naive patients with hormone receptor-positive advanced breast cancer.	27908454
POTTR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Goserelin	Standard of care. Randomised clinical trial. N=138 (136 eligible). Goserelin resulted in similar FFS and OS as surgical ovariectomy in premenopausal patients with ER and/or PgR-positive metastatic breast cancer.	9508182
GIMR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Letrozole	Restricted benefit: HR-positive metastatic breast cancer.	11352951
POTTR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Medroxyprogesterone Acetate	Standard of care. Randomised phase 3 trials compared the efficacy of megestrol acetate or medroxyprogesterone acetate with tamoxifen in postmenopausal women with advanced breast cancer, showing similar response rates (25-44% vs 31-35%) and median survival times (20-24 months vs 26-32 months), with some subgroup differences in response.	3292710, 2939943, 8943670
POTTR	2020-04-16	FL	1	ESR1	Protein expression	Breast cancer	Tamoxifen	Standard of care. Tamoxifen showed a 32% response rate in 59 postmenopausal women with advanced breast cancer, with tumors containing estrogen receptors and those responding to previous hormonal manipulation more likely to respond (60% and 69%, respectively).	326386, 931204
GIMR	2025-05-26	FL	1	ESR1+ERBB2	ESR1:Protein expression and ERBB2:Protein expression and NOT ERBB2:amplification, ESR1:Protein expression and ERBB2:Low protein expression and NOT ERBB2:amplification, ESR1:Protein expression and ERBB2:Ultra-low protein expression	Breast cancer	Trastuzumab deruxtecan	TGA approved. FDA approved. Phase 3 DESTINY-Breast06 trial. NCT04494425. N=866. Trastuzumab deruxtecan significantly improved PFS over chemotherapy (13.2 versus 8.1 months) in patients with hormone receptor-positive, HER2-low metastatic breast cancer who had received endocrine-based therapy. HER2 status is defined by Ventana's Pathway anti-HER-2 (4B5) Rabbit Monoclonal Primary Antibody. HER2-ultralow is IHC 0 with membrane staining, and HER2-low is IHC 1+ or IHC 2+/ISH-negative.	39282896
POTTR	2020-04-16	FL	1	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Abemaciclib + Fulvestrant	TGA approved. PBS reimbursed. Phase 3 MONARCH 2 trial. NCT02107703. N=669. Abemaciclib + fulvestrant significantly improved PFS (16.4 vs 9.3 months) and ORR (48.1% vs 21.3%) compared to placebo + fulvestrant in HR+/HER2- advanced breast cancer patients who progressed on endocrine therapy.	28580882
POTTR	2020-04-16	FL	1	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Palbociclib + Fulvestrant	TGA approved. PBS reimbursed. Phase 3 PALOMA-3 trial. NCT01942135. N=521. Fulvestrant plus palbociclib significantly improved progression-free survival (9.5 vs 4.6 months) in hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy, across PIK3CA mutational status and hormone-receptor expression levels.	26947331
POTTR	2020-04-16	FL	1	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Ribociclib + Fulvestrant	TGA approved. PBS reimbursed. Phase 3 MONALEESA-3 trial. NCT02422615. N=726. Ribociclib plus fulvestrant significantly improved PFS (20.5 months vs 12.8 months) over placebo plus fulvestrant in hormone receptor-positive, HER2-negative advanced breast cancer patients, with consistent effects in treatment-naive and pretreated patients. This combination also showed a significant overall survival benefit (HR, 0.72) with an estimated overall survival at 42 months of 57.8% versus 45.9%.	29860922, 31826360
GIMR	2020-05-01	FL	1	ESR1+ERBB2	NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Triple-negative breast cancer	Sacituzumab Govitecan	TGA approved; Not PBS reimbursed. FDA approved. Phase 3 ASCENT trial (NCT02574455, N=468): Sacituzumab govitecan significantly improved PFS (5.6 vs 1.7 months) and OS (12.1 vs 6.7 months) over single-agent chemotherapy in metastatic triple-negative breast cancer, with an ORR of 35%.	30786188, 33882206
GIMR	2020-04-16	FL/XT	1	FLT3	D835, I836, Internal tandem duplication	Acute myeloid leukaemia	Gilteritinib	PBS reimbursed. Phase 1-2 trial (NCT02014558) demonstrated gilteritinib was well tolerated in patients with relapsed or refractory acute myeloid leukaemia, with a maximum tolerated dose of 300mg/day, consistent FLT3 inhibition and antileukaemic activity, achieving 40% response rate. Phase 3 trial (NCT02421939, N=371) showed gilteritinib significantly improved overall survival (9.3 vs 5.6 months) and complete remission with full or partial hematologic recovery (34.0% vs 15.3%) compared to salvage chemotherapy in patients with relapsed or refractory FLT3-mutated AML.	28645776, 31665578
GIMR	2020-04-16	FL	1	FLT3	Internal tandem duplication, Kinase domain mutation	Acute myeloid leukaemia	Midostaurin	TGA approved. PBS reimbursed. Maintenance treatment as a single-agent.	28644114
GIMR	2022-01-28	FL	1	HLA-A2	A*02:01	Uveal melanoma	Tebentafusp	TGA approved. PBS reimbursed. Phase 3. IMCgp100-202. NCT03070392. N=378. OS rate at 1 year was 73% in the tebentafusp group versus 59% in the control group. PFS rate at 6 months was 31% (tebentafusp) vs 19%.	34551229
GIMR	2023-10-29	FL	1	HLA-A2	A*02:01	Uveal melanoma	Tebentafusp	TGA approved. PBS reimbursed. Phase 3 trial. IMCgp100-202. NCT03070392. HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. Median OS was significantly longer in tebentafusp group compared to control (21.6 versus 16.9 months). ORR was 14% (Control 5%).	37870955
GIMR	2020-05-04	FL	1	Homologous Recombination Deficiency Score	High	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Niraparib	TGA approved. PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012: HRD was determined using myChoice HRD test with cut-off score of 42-100. Note: the HR proficient group also derives benefits from Niraparib.In an updated analysis at median follow-up of 73.9 months, 5-year PFS rates favored niraparib overall (22% vs 12%) and in HRd patients (35% vs 16%). In BRCA-mutated patients showed PFS HR of 0.43, with 5-year PFS rates of 37% vs 14%.	31562799, 39284381
GIMR	2020-05-27	FL	1	IDH1	R132	Cholangiocarcinoma	Ivosidenib	TGA approved. PBS listed. FDA approved (2021-08-25). Phase 3 ClarIDHy trial: PFS improvement was shown in the ivosidenib group (2·7 months) vs placebo (1·4 months). Update 2025-07-07.	32416072
GIMR	2023-07-31	FL	1	IDH1	R132	Cholangiocarcinoma	Ivosidenib	TGA approved. PBS listed. Phase 3. ClarIDHy trial. Final OS result. In IDH1 mutant cholangiocarcinoma patients, Ivosidenib resulted in median OS of 10.3 months vs 7.5 months (placebo; adjusted for crossover 5.1 months). Update 2025-07-07	34554208
GIMR	2020-06-15	FL	1	JAK2	V617F	Myelofibrosis	Ruxolitinib	PBS reimbursed for intermediate-1 or higher risk myelofibrosis, but not dependent on JAK status. COMFORT-I. 	22375971
GIMR	2020-05-07	FL	1	KIT	Protein expression	Gastrointestinal stromal tumour	Imatinib	PBS reimbursed based on CD117 (c-KIT) IHC. Phase 2 trial. N=147. Imatinib mesylate resulted in a partial response in 53.7% of patients with advanced gastrointestinal stromal tumors, with median duration of response not reached after 24 weeks, and was well tolerated with mild-to-moderate adverse effects.	12181401
GIMR	2020-05-07	FL	1	KIT	Protein expression	Gastrointestinal stromal tumour	Sunitinib	PBS reimbursed based on CD117 (c-KIT) IHC. Randomised controlled Phase 3 trial. NCT00075218. N=312. Median time to tumour progression was 27.3 weeks with sunitinib versus 6.4 weeks with placebo (HR 0.33; p<0.0001) in imatinib-resistant or intolerant gastrointestinal stromal tumour.	17046465
GIMR	2020-05-20	FL	1	KIT	Protein expression; Oncogenic mutations	Gastrointestinal stromal tumour	Ripretinib	TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors. Phase3 INVICTUS trial. NCT03353753. Ripretinib significantly improved median PFS (6.3 months vs 1.0 month) compared with placebo in patients with advanced gastrointestinal stromal tumours resistant to approved treatments.	31085175, 32511981, 32804590, 10.1158/1538-7445.AM2018-3925
GIMR	2020-04-16	FL	1	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	Cetuximab; Panitumumab; Cetuximab + Irinotecan; Cetuximab + FOLFIRI	PBS reimbursed for RAS-wild-type metastatic colorectal cancers. N=329. Cetuximab plus irinotecan had a significantly higher ORR (22.9% vs 10.8%) and longer median TTP (4.1 vs 1.5 months) compared to cetuximab monotherapy in irinotecan-refractory metastatic colorectal cancer. In a meta-analysis of 9 RCTs (N=5948). anti-EGFR mAb therapy significantly improved PFS (HR 0.62) and OS (HR 0.87) in mCRC tumors without any RAS mutations, while no benefit was evident in tumors with RAS mutations.	25115304, 15269313
GIMR	2022-01-30	FL	1	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	FOLFIRI + Cetuximab	TGA approved. FDA approved. Phase 3 trial. CRYSTAL. NCT00154102. N=1198. Cetuximab + FOLFIRI reduced risk of progression of metastatic colorectal cancer compared to FOLFIRI alone (HR 0.85), with significant benefit in patients with wild-type KRAS tumors (HR 0.68).	19339720
GIMR	2022-06-07	FL	1	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	FOLFOX + Panitumumab	Panitumumab is TGA approved. Phase 3 PARADIGM trial (NCT02394795). In previously untreated KRAS wild-type metastatic colorectal cancer, Panitumumab significantly improved OS over bevacizumab in both left-sided tumour (37.9 v 34.3 months) and full analysis set populations (36.2 v 31.3 months).	37071094, 10.1200/JCO.2022.40.17_suppl.LBA1
GIMR	2026-03-04	FL	1	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	FOLFOXIRI + Panitumumab; FOLFOX + Panitumumab	Phase 3 TRIPLETE study. NCT03231722. N=435. Upfront mFOLFOXIRI plus panitumumab significantly improved OS (41.1 months) compared with mFOLFOX/panitumumab (33.3 months) in RAS/BRAF wild-type mCRC. ORR was 78% (experimental) vs 75% (control). No differences in PFS (HR, 0.95), early tumor shrinkage, depth of response, and no residual tumor resection rate.	41505697
GIMR	2021-04-23	FL	1	Microsatellite Instability	High	Endometrial cancer	Dostarlimab	FDA approved 09/02/2023. GARNET trial (NCT02715284, Phase 1, N=104): Dostarlimab showed an ORR of 42.3% (30/71) in dMMR/MSI-H endometrial cancer as assessed by IHC, PCR or NGS, with 12.7% CR and 29.6% PR. Median DOR not reached, with 96.4% and 76.8% of responses sustained at 6 and 12 months respectively. 	33001143
GIMR	2023-12-16	FL	1	Microsatellite Instability	High	Endometrial cancer	Dostarlimab + Carboplatin + Paclitaxel	Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. The dual primary endpoint of OS at 24 months was 83% with dostarlimab and 59% with placebo, and was significantly improved over placebo with a hazard ratio of 0.69 at the updated analysis.	36972026, 38866180
GIMR	2022-01-17	FL	1	Microsatellite Instability	High	Endometrial cancer	Pembrolizumab	Not TGA approved. FDA approved. Phase 2. NCT02628067. KEYNOTE-158, pooled analysis from Cohort D and K. N=79. ORR 48%. Median PFS: 13.1 months. Median DOR: not reached. Median OS: Not reached.	34990208
GIMR	2020-12-11	FL	1	Microsatellite instability+Mismatch repair	NOT Microsatellite instability:high AND NOT Mismatch repair:deficient	Endometrial cancer	Lenvatinib + Pembrolizumab	PBS reimbursed. TGA approved. FDA Approved. In KEYNOTE-146: ORR was 38% (out of 94 patients) including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS). In the confirmatory trial (KEYNOTE-775), primary point was met in non-MSI-H/dMMR patients who have progressed through one previous line of platinum-based chemotherapy: median PFS was 6.6 (pembrolizumab + lenvatinib) vs 3.8 months (investigator choice of chemotherapy) and median OS: 17.4 vs 12 months (chemotherapy). ORR: 30% vs 15%. Note Benefits were seen in both pMMR and dMMR populations, and the TGA approval was irrespective of MMR status.	30922731, 32167863
GIMR	2020-12-11	FL	1	Mismatch repair	Deficient	Colorectal adenocarcinoma	Pembrolizumab	PBS listed. TGA approved. KEYNOTE-177: First-line treatment. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. With an effective crossover rate of 62%, median OS was 77.5 v 36.7 months with chemotherapy (HR=0.73). MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.	33264544, 39631622, 10.1200/JCO.2020.38.18_suppl.LBA4
GIMR	2020-12-10	FL	1	Mismatch repair	Deficient	Colorectal adenocarcinoma	Pembrolizumab	PBS listed. TGA approved. KEYNOTE-164: KEYNOTE-164: In previously treated metastatic colorectal cancer, ORR was 33% and median OS was 31.4mo. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.	31725351
GIMR	2021-04-23	FL	1	Mismatch repair	Deficient	Endometrial cancer	Dostarlimab	TGA approved. PBS reimbursed. FDA approved. Phase 1 trial. GARNET. NCT02715284. N=71. Dostarlimab demonstrated an objective response rate of 42.3-43% (30 patients) with 12.7-13% complete response and 29.6% partial response in patients with mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) endometrial cancer as assessed by IHC, PCR, or NGS. Duration of response was 96.4% at 6 months and 76.8% at 12 months with an acceptable safety profile.	33001143
GIMR	2023-12-16	FL	1	Mismatch repair	Deficient	Endometrial cancer	Dostarlimab + Carboplatin + Paclitaxel	TGA approved. PBS reimbursed. Phase 3 RUBY trial. NCT03981796. N=494. Dostarlimab plus carboplatin-paclitaxel significantly improved PFS over placebo. In the dMMR/MSI-H population, PFS at 24 months was 61% with dostarlimab and 16% with placebo. OS at 24 months was 83% with dostarlimab and 59% with placebo.	36972026
GIMR	2020-12-11	FL	1	Mismatch repair	Deficient	Endometrial cancer	Lenvatinib + Pembrolizumab	PBS reimbursed. TGA approved. FDA Approved. In KEYNOTE-775, median PFS was 10.7 v 3.7 months and OS was not reached vs 8.6 months for dMMR population. Note Benefits were seen in both pMMR and dMMR populations, and the TGA approval was irrespective of MMR status.	30922731, 32167863
GIMR	2021-02-15	FL	1	NECTIN4	Protein expression	Urothelial carcinoma	Enfortumab Vedotin	TGA approved. PBS reimbursed. In Phase 2 EV-201 trial (N=125), enfortumab vedotin showed a confirmed objective response rate of 44% with 12% complete responses in patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum and anti-PD-1/L1 therapy. In registrational Phase 3 EV-301 trial (NCT03474107, N=608), enfortumab vedotin significantly prolonged overall survival (12.88 months vs 8.97 months) and progression-free survival (5.55 vs 3.71 months) compared to chemotherapy in patients with advanced urothelial carcinoma previously treated with platinum-containing chemotherapy and PD-1 or PD-L1 inhibitor. Nectin-4 expression was not required for trial entry, given that it is highly expressed on majority of urothelial carcinoma cells.	31356140, 33577729
GIMR	2020-04-16	FL	1	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis 	Selumetinib	TGA approved. PBS reimbursed for paediatric patients with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Phase 2. NCT01089101. N=50. Selumetinib achieved sustained partial response in 36% (9/25) of patients with BRAF-aberrant pilocytic astrocytoma and 40% (10/25) of patients with NF1-associated paediatric low-grade glioma.	31151904
GIMR	2025-06-09	FL	1	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis 	Selumetinib	Phase 3 KOMET trial. NCT04924608. N=145. Selumetinib significantly improved ORR (19.7% vs 5.4%) compared to placebo in adults with NF1 and symptomatic, inoperable plexiform neurofibroma.	10.1200/JCO.2025.43.16_suppl.3014
GIMR	2020-11-10	FL	1	NTRK1	Fusions, ATP1A4-NTRK1 fusion, CD74-NTRK1 fusion, CTRC-NTRK1 fusion, DDR2-NTRK1 fusion, DIAPH1-NTRK1 fusion, EPS15-NTRK1 fusion, GON4L-NTRK1 fusion, IRF2BP2-NTRK1 fusion, LMNA-NTRK1 fusion, NFASC-NTRK1 fusion, PDE4DIP-NTRK1 fusion, PLEKHA6-NTRK1 fusion, PPL-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM63-NTRK1 fusion 	Solid tumours; Mammary analogue secretory carcinoma; Breast secretory carcinoma	Larotrectinib	TGA approved. PBS reimbursed 1/7/22 for paediatric solid tumours and adult mammary analogue secretory carcinoma of salivary gland and secretary breast carcinoma. NCT02122913, NCT02637687, NCT02576431	29466156, 32105622, 10.1200/JCO.2019.37.15_suppl.10010
GIMR	2020-11-10	FL	1	NTRK2	Fusions, GNAQ-NTRK2 fusion, RBPMS-NTRK2 fusion, STRN-NTRK2 fusion, TRAF2-NTRK2 fusion	Solid tumours; Mammary analogue secretory carcinoma; Breast secretory carcinoma	Larotrectinib	TGA approved. PBS reimbursed 1/7/22 for paediatric solid tumours and adult mammary analogue secretory carcinoma of salivary gland and secretary breast carcinoma. NCT02122913, NCT02637687, NCT02576431	29466156, 32105622, 10.1200/JCO.2019.37.15_suppl.10010
GIMR	2020-11-10	FL	1	NTRK3	Fusions, ARNT2-NTRK3 fusion, EML4-NTRK3 fusion, ETV6-NTRK3 fusion, IQGAP1-NTRK3 fusion, MYO5A-NTRK3 fusion, SPECC1L-NTRK3 fusion, SQSTM1-NTRK3 fusion, TFG-NTRK3 fusion, TPM4-NTRK3 fusion	Solid tumours; Mammary analogue secretory carcinoma; Breast secretory carcinoma	Larotrectinib	TGA approved. PBS reimbursed 1/7/22 for paediatric solid tumours and adult mammary analogue secretory carcinoma of salivary gland and secretary breast carcinoma. NCT02122913, NCT02637687, NCT02576431	29466156, 32105622, 10.1200/JCO.2019.37.15_suppl.10010
GIMR	2020-04-16	FL	1	PDGFB	COL1A1-PDGFB Fusion	Dermatofibrosarcoma protuberans	Imatinib	TGA approved. PBS reimbursed. Imatinib demonstrates activity against dermatofibrosarcoma protuberans characterised by the COL1A1-PDGFB fusion gene.	19707305
GIMR	2020-04-16	FL	1	PDGFRA	FIP1L1-PDGFRA Fusion; Fusion	Chronic eosinophilic leukaemia	Imatinib	TGA approved. PBS reimbursed. Phase 2 study. Imatinib was effective in treating CEL with FIP1L1-PDGFRA or PDGFRB fusion genes, achieving 95% CHR and 75-87% CMR, with no molecular relapse observed at a median follow-up of 26.7 months, while HES patients without known molecular aberration showed a lower response rate.	18950453
POTTR	2020-04-16	FL	1	PGR	Protein expression	Breast cancer	Tamoxifen; Letrozole; Anastrozole; Exemestane; Medroxyprogesterone Acetate; Goserelin	Standard of care.	326386, 931204, 3292710, 2939943, 8943670, 9508182, 11745278, 11352951, 10735887
GIMR	2020-06-18	FL	1	PGR	Protein expression	Endometrial cancer	Medroxyprogesterone Acetate	Standard of care. Phase 3 dose-response study. N=299. Oral medroxyprogesterone acetate (MPA) showed response rates of 25% (low-dose, 200mg/d) versus 15% (high-dose, 1000mg/d) in advanced or recurrent endometrial carcinoma, with median PFS of 3.2 and 2.5 months, and median OS of 11.1 and 7.0 months, respectively.	10561210
GIMR	2023-10-29	FL	1	RET	Fusion, KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, KIF13A-RET fusion, KIAA1549L-RET fusion, KIAA1468-RET fusion, PRKAR1A-RET fusion	Non-small cell lung cancer	Selpercatinib	TGA approved. Not PBS reimbursed. Phase 3 trial. LIBRETTO-431. NCT04194944. N=261. Selpercatinib (1st line) improved PFS over chemoimmunotherapy (24.8 vs 11.2 months). ORR was similar between the two arms at 84% and 65%. The cause-specific hazard ratio for the time to CNS progression was 0.28.	37870973
GIMR	2020-05-08	FL	1	RET	Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion	Non-small cell lung cancer	Selpercatinib	TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. Phase 1-2 LIBRETTO-001 trial. NCT03157128. Selpercatinib showed an ORR of 64% in 105 previously treated RET fusion-positive NSCLC patients and 85% in 39 previously untreated patients, with durable responses and intracranial activity.	32846060, 10.1200/JCO.2020.38.15_suppl.3584
GIMR	2020-04-25	FL	1	ROS1	Fusions	Non-small cell lung cancer	Crizotinib	PBS reimbursed. ROS1-positivity is defined as gene rearrangement >15% positive cells by FISH	25264305
GIMR	2020-11-10	FL	1	ROS1	Fusions	Non-small cell lung cancer	Entrectinib	PBS reimbursed. ROS1-positivity is defined as gene rearrangement >15% positive cells by FISH. In combined analysis of ALKA-372-001, STARTRK-1, and STARTRK-2, ORR was 71% wit hmedian DOR of 24.6 months.	28183697, 31838015, 10.1200/jco.2015.33.15_suppl.2517
GIMR	2020-06-15	FL	1	SSTR2	Protein expression	Pancreatic neuroendocrine tumour; Neuroendocrine tumour	Lanreotide	PBS reimbursed. CLARINET. Well-to-moderately-differentiated with a positive Octreotide scan.	25014687
GIMR	2020-06-15	FL	1	SSTR2	Protein expression	Pancreatic neuroendocrine tumour; Neuroendocrine tumour	Octreotide	PBS reimbursed. PROMID trial. Well-differentiated metastatic midgut tumors. No significant OS differences between treatment arms due to cross-over.	19704057, 26731483
GIMR	2020-06-15	FL	1	TNFRSF8	Protein expression	Anaplastic large cell lymphoma 	Brentuximab Vedotin	PBS reimbursed. Phase 2 trial. N=58. Brentuximab vedotin induced objective responses in 86% of patients and CRs in 57% with relapsed/refractory systemic ALCL, with median duration of response of 12.6 months, targeting CD30-positive malignant cells.	22614995
GIMR	2020-06-15	FL	1	TNFRSF8	Protein expression	Cutaneous T-cell lymphoma	Brentuximab Vedotin	PBS reimbursed. Phase 3 ALCANZA trial. NCT01578499. N=128. Brentuximab vedotin significantly improved objective global response lasting at least 4 months compared to physician's choice (56.3% vs 12.5%) in CD30-positive cutaneous T-cell lymphoma patients.	28600132
GIMR	2020-06-15	FL	1	TNFRSF8	Protein expression	Hodgkin’s lymphoma	Brentuximab Vedotin	PBS reimbursed for R/R disease. Phase 3 AETHERA trial: Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation significantly improved PFS (HR 0.57) in patients with Hodgkin's lymphoma at risk of relapse or progression.	22454421, 25796459
GIMR	2020-06-23	FL	1	TSC1	Oncogenic mutations (germline)	Solid tumours; Subependymal giant cell astrocytoma	Everolimus	PBS reimbursed. SEGA or visceral tumours in patients with tuberous sclerosis complex. EXIST-1.	23158522, 23325902
GIMR	2020-06-23	FL	1	TSC2	Oncogenic mutations (germline)	Solid tumours; Subependymal giant cell astrocytoma	Everolimus	PBS reimbursed. SEGA or visceral tumours in patients with tuberous sclerosis complex. EXIST-1.	23158522, 23325902
GIMR	2023-07-24	FL	1	VHL	Oncogenic mutations (germline)	Hemangioblastoma	Belzutifan	TGA approved. PBS listed. FDA approved. Phase 2. NCT03401788. LITESPARK-004. Updated results. Belzutifan showed antitumor activity in VHL-associated renal cell carcinoma and other neoplasms. Updated results from CNS hemangioblastomas ORR 44%, DCR 90%, time 5.4 months, median PFS was not reached.	10.1200/JCO.2023.41.16_suppl.2008
GIMR	2021-12-02	FL	1	VHL	Oncogenic mutations (germline)	Pancreatic neuroendocrine tumour; Hemangioblastoma	Belzutifan	TGA approved. PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas.	34818478, 10.1200/JCO.2021.39.15_suppl.4555
GIMR	2021-09-15	FL	1	VHL	Oncogenic mutations (germline)	Renal cell carcinoma	Belzutifan	TGA approved. PBS listed. FDA approved 2021-08-13. MK-6482-004. N=61. ORR 49% (30/61) for clear cell renal cell carcinomas. PFS rate at 52 week 98%. 	34818478, 10.1200/JCO.2021.39.15_suppl.4555, 10.1200/JCO.2020.38.15_suppl.5003
GIMR	2020-05-21	FL	1B	ABL1	BCR-ABL1 Fusion	Chronic myelogenous leukaemia	Bosutinib	TGA approved. Not PBS reimbursed. Third or later line treatment. BFORE trial.	29091516
GIMR	2020-04-16	FL	1B	BRAF	V600E	Anaplastic thyroid cancer 	Dabrafenib + Trametinib	TGA approved. Not PBS reimbursed. Phase 2 trial. N=16. Dabrafenib + Trametinib showed a confirmed ORR of 69% in patients with BRAF V600E-mutated anaplastic thyroid cancer, with 12-month estimates of DOR, PFS, and OS being 90%, 79%, and 80% respectively.	29072975
GIMR	2020-05-15	FL	1B	BRAF	V600E, V600K	Melanoma	Trametinib	TGA approved. PBS reimbursement must include concomitant dabrafenib. Phase 3 trial. NCT01245062. N=322. Trametinib improved PFS (4.8 months vs 1.5 months) and OS (81% vs 67% at 6 months) compared to chemotherapy in patients with BRAF V600E or V600K mutated metastatic melanoma. Single agent NOT recommended.	22663011
GIMR	2020-04-16	FL	1B	BRCA1	Oncogenic mutations (germline)	Breast cancer	Olaparib	TGA approved. Not PBS reimbursed. Phase 3 OlympiAD trial. NCT02000622. N=302. Olaparib monotherapy significantly improved PFS (7.0 vs 4.2 months) and ORR (59.9% vs 28.8%) compared to standard therapy in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation.	28578601
GIMR	2020-05-04	FL	1B	BRCA1	Oncogenic mutations (germline)	Breast cancer	Talazoparib	TGA approved. Not PBS reimbursed. Phase 3 EMBRACA trial. NCT01945775. N=431. Talazoparib significantly improved PFS (8.6 vs 5.6 months) and ORR (62.6% vs 27.2%) over standard single-agent therapy in patients with advanced breast cancer and germline BRCA1/2 mutation.	30110579
GIMR	2020-04-25	FL	1B	BRCA1	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Olaparib	TGA approved. Phase 3 POLO trial. NCT02184195. N=154. Olaparib maintenance therapy did not show a statistically significant OS benefit (19.0 vs 19.2 months) versus placebo in germline BRCA-mutated metastatic pancreatic cancer, but showed a clinically meaningful benefit in time to first subsequent cancer therapy or death (HR, 0.44) and long-term survival in a subset of patients.	31157963, 35834777
GIMR	2020-04-16	FL	1B	BRCA2	Oncogenic mutations (germline)	Breast cancer	Olaparib	TGA approved. Not PBS reimbursed. Phase 3 OlympiAD trial. NCT02000622. N=302. Olaparib monotherapy significantly improved PFS (7.0 vs 4.2 months) and ORR (59.9% vs 28.8%) compared to standard therapy in patients with HER2-negative metastatic breast cancer and a germline BRCA mutation.	28578601
GIMR	2020-05-04	FL	1B	BRCA2	Oncogenic mutations (germline)	Breast cancer	Talazoparib	TGA approved. Not PBS reimbursed. Phase 3 EMBRACA trial. NCT01945775. N=431. Talazoparib significantly improved PFS (8.6 vs 5.6 months) and ORR (62.6% vs 27.2%) over standard single-agent therapy in patients with advanced breast cancer and germline BRCA1/2 mutation.	30110579
GIMR	2020-04-25	FL	1B	BRCA2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Olaparib	TGA approved. Phase 3 POLO trial. NCT02184195. N=154. Olaparib maintenance therapy did not show a statistically significant OS benefit (19.0 vs 19.2 months) versus placebo in germline BRCA-mutated metastatic pancreatic cancer, but showed a clinically meaningful benefit in time to first subsequent cancer therapy or death (HR, 0.44) and long-term survival in a subset of patients.	31157963, 35834777
GIMR	2021-07-03	FL	1B	CCR4	Protein expression	Cutaneous T-cell lymphoma; Sézary syndrome; Mycosis fungoides	Mogamulizumab	FDA approved. Phase 3 MAVORIC trial. Comparing with vorinostat, mogalizumab extended the PFS to 7.7 vs 3.1 months (vorinostat) in previously treated cutaneous T-cell lymhpomas. Exploratory analysis showed that CCR4 expression was ubiquitously expressed (97% had at least 10% infiltrating lymphoid cells), but CCR4 was not a requirement for participation.	30100375
GIMR	2020-06-15	FL	1B	CD20	Protein expression	Chronic lymphocytic leukaemia	Ibrutinib + Rituximab	TGA approved. Not PBS reimbursed. Phase 3 trial. NCT02048813. N=529. Ibrutinib-rituximab resulted in superior PFS (89.4% vs 72.9% at 3 years) and OS (98.8% vs 91.5% at 3 years) compared to chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab in patients with previously untreated CLL.	31365801
GIMR	2020-06-15	FL	1B	CD20	Protein expression	Waldenstroms macroglobulinaemia	Ibrutinib; Ibrutinib + Rituximab	Phase 3. iNNOVATE trial. N=150. Ibrutinib plus Rituximab significantly improved PFS (HR, 0.20) and major response rate (72% vs 32%) compared to placebo plus Rituximab in both previously treated and untreated Waldenstrom's macroglobulinemia patients.	29856685
POTTR	2020-04-16	FL	1B	CD274	Protein expression	Cervical cancer	Pembrolizumab	TGA approved. In the Phase 1b KEYNOTE-028 trial (NCT02054806; n=24) in PD-L1-positive advanced cervical cancer, pembrolizumab achieved an ORR of 17% (4 confirmed partial responses; 3 stable disease). In the Phase 2 KEYNOTE-158 study (NCT02628067; n=98) in previously treated advanced cervical cancer, pembrolizumab produced an ORR of 12.2% (3 complete responses; 9 partial responses), with all responses occurring in tumors with CPS ≥ 1% by 22C3 pharmDx assay (ORR 15% in PD-L1-positive cohort).	29095678, 30943124, 10.1200/JCO.2018.36.15_suppl.5522
GIMR	2020-09-29	FL	1B	CD274	Protein expression	Oesophageal cancer; Oesophageal Adenocarcinoma; Oesophageal squamous cell carcinoma	Pembrolizumab + Cisplatin + Fluorouracil	TGA approved. Phase 3 KEYNOTE-590. FDA approved 2021-03-22. In the first-line setting, adding pembrolizumab to chemotherapy resulted in superior OS in PD-L1 positive subgroups (defined as CPS ≥ 10%, median 13.5 versus 9.4 mo), but also in ESCC and overall populations. Overall ORR in pembrolizumab arm was 45% (vs control 23%).	10.1016/j.annonc.2020.08.2298
GIMR	2020-04-27	FL	1B	CD274	Protein expression	Triple-negative breast cancer	Atezolizumab + Nab-paclitaxel	TGA provisional approval based on PFS data. Not PBS reimbursed. IMpassion130. PD-L1 positive is defined as >= 1% immune cells as percentage of tumour area. (IC1/2/3). Note: In the ITT population, the OS was 21.0 months in the Atezolizumab group vs 18.7 months in the placebo group (not statistically significant), with an exploratory signal of OS improvement seen in the subgroup analysis in the PD-L1 IC-positive population (25.4 vs 17.9 months).	30345906, 34219000
GIMR	2020-04-25	FL	1B	CD274	Protein expression	Urothelial carcinoma	Atezolizumab	TGA approved. Not PBS reimbursed. IMVigor211. PD-L1 positivity defined as stained tumour-infiltrating immune cells covering >= 5% of the tumour area. (IC2 or IC3)	26952546
GIMR	2020-05-20	FL	1B	CD274+EGFR+ALK	CD274:Protein expression and NOT EGFR:Oncogenic mutations and NOT ALK:fusion	Non-small cell lung cancer	Nivolumab + Ipilimumab	TGA approved; FDA approved; Checkmate 227. PD-L1 positivity defined as >= 1% of tumour cells using Dako 28-8 pharmDx assay. EGFR and ALK negative	31562796
GIMR	2020-06-17	FL	1B	CD33	Protein expression	Acute myeloid leukaemia	Gemtuzumab Ozogamicin	TGA approved. Not PBS reimbursed. Phase 3 AAML0531 trial (N=1022) demonstrated that gemtuzumab ozogamicin, a CD33-targeted immunoconjugate, added to chemotherapy improved event-free survival (53.1% vs 46.9%) by reducing relapse risk (32.8% vs 41.3%) in children and adolescents with de novo acute myeloid leukemia.	25092781
GIMR	2025-07-30	FL	1B	CD38	Overexpression	Multiple myeloma	Daratumumab + Bortezomib + Lenalidomide + Dexamethasone	Phase 3 PERSEUS trial. NCT03710603. N=709. Subcutaneous daratumumab added to VRd induction, consolidation, and lenalidomide maintenance significantly improved PFS (84.3% vs 67.7% at 48 months, HR 0.42) and ORR (87.9% vs 70.1%) and MRD-neg ative rate (75.2% vs 47.5%) in transplantation-eligible newly diagnosed multiple myeloma. Note that CD38 is a constitutively expressed target in myeloma and is not required for therapy selection.	38084760
GIMR	2020-06-15	FL	1B	CD38	Overexpression	Multiple myeloma	Daratumumab + Lenalidomide + Dexamethasone	TGA approved. Phase 3 POLLUX trial. NCT02076009. N=569. Daratumumab + lenalidomide + dexamethasone significantly improved PFS (HR, 0.37) and ORR (92.9% vs 76.4%) compared to lenalidomide + dexamethasone in patients with relapsed or refractory multiple myeloma.	27705267, 27307294
GIMR	2020-06-15	FL	1B	CD38	Overexpression	Multiple myeloma	Isatuximab-irfc + Pomalidomide + Dexamethasone	TGA approved. Phase 3 ICARIA-MM study. N = 307. Isatuximab + pomalidomide-dexamethasone significantly improved median PFS (11.5 months) compared to pomalidomide-dexamethasone (6.5 months) with HR of 0.596 in relapsed and refractory multiple myeloma patients.	31735560
GIMR	2020-06-15	FL	1B	CD79B	Protein expression	Diffuse large B-cell lymphoma	Polatuzumab vedotin + Bendamustine + Rituximab	Standard of care. TGA approved but not based on biomarker. Phase Ib/II trials demonstrated that polatuzumab vedotin combined with bendamustine and rituximab (pola-BR) achieved superior outcomes compared to bendamustine and rituximab in transplantation-ineligible relapsed/refractory diffuse large B-cell lymphoma patients: complete response rate (40.0% vs 17.5%), progression-free survival (median 9.5 vs 3.7 months), and overall survival (median 12.4 vs 4.7 months). While CD79B is prognostic, CD79B expression alone does not correlate with response degree.	25925619, 31693429
GIMR	2024-05-19	FL	1B	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Amivantamab + Carboplatin + Pemetrexed; Amivantamab + Carboplatin + Pemetrexed + Lazertinib	Phase 3. NCT04988295. MARIPOSA-2: Amivantamab and chemotherapy with or without lazertinib prolonged PFS for EGFR-mutant advanced NSCLC patients after progression on osimeterinib, versus chemotherapy alone (median PFS by investigator, 8.3, 8.3, and 4.2 months). ORR was higher (64% and 63% vs 36%). OS for amivantamab-lazertinib was significantly improved (HR 0.75, 3-year OS 60% vs 51%), with increased grade 3 or higher adverse events (80% vs 52%).	37879444, 40923797
GIMR	2025-07-30	FL	1B	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 3. MARIPOSA. NCT04487080. N=1074. In previously untreated EGFR-mutated NSCLC, a 2:2:1 randomized trial compared amivantamab-lazertinib vs osimertinib vs lazertinib. Amivantamab-lazertinib demonstrated superior PFS compared to osimertinib (23.7 vs 16.6 months; HR 0.70, 95% CI 0.58–0.85). ORR was similar between groups (86% vs 85%), but median response duration favored amivantamab-lazertinib (25.8 vs 16.8 months). OS HR was 0.80 (95% CI 0.61–1.05). 	38924756
GIMR	2023-11-09	FL	1B	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Osimertinib	Phase 3 FLAURA2 trial. NCT04035486. N=557. Combination of osimertinib with pemetrexed and a platinum agent led to significantly longer PFS over osimertinib monotherapy (19.3 v 11.2 months). ORR was similar between arms at 80% (osimertinib) and 84% (combination). Osimertinib plus chemotherapy significantly improved OS (47.5 months) compared to osimertinib monotherapy (37.6 months) in EGFR-mutated advanced NSCLC, with a HR of 0.77.	37937763, 41104938
GIMR	2020-05-12	FL	1B	ERBB2	Amplification	Breast cancer	Capecitabine + Trastuzumab + Tucatinib	TGA approved; Not PBS reimbursed. FDA approved; HER2Climb: PFS: 7.8 (tucatinib) v 5.6 (placebo) months and OS 21.9 v 17.4 month. In the final OS analysis, median OS was also siginificantly longer (24.7 months in the tucatinib combination group) vs 19.2 months (placebo combination group).	29804905, 31825569, 32468955, 34954044, 10.1200/JCO.2020.38.15_suppl.1005
GIMR	2020-05-04	FL	1B	ERBB2	Amplification	Breast cancer	Lapatinib + Paclitaxel	TGA approved. Not PBS reimbursed. Phase 3. NCT00281658. Lapatinib + paclitaxel significantly improved OS (27.8 vs 20.5 months), PFS (9.7 vs 6.5 months), and ORR (69% vs 50%) compared to placebo + paclitaxel in HER2-positive metastatic breast cancer patients. HER2 positivity determined by FISH.	23509322
GIMR	2021-06-06	FL	1B	ERBB2	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Pembrolizumab + Trastuzumab + Cisplatin + Fluorouracil; Pembrolizumab + Trastuzumab + Capecitabine + Oxaliplatin	TGA approved. Not PBS reimbursed. FDA approved 5/5/2021. Phase 3: KEYNOTE-811 (NCT03615326). First interim analysis. ORR 74% for pembro + SOC vs 52% for SOC alone. DOR 10.6 vs 9.5mo.	34912120, 10.1200/JCO.2021.39.15_suppl.4013
GIMR	2020-05-04	FL	1B	ERBB2	Amplification, Overexpression	Breast cancer	Lapatinib + Letrozole	TGA approved. Not PBS reimbursed. HER2 positivity is defined as IHC 3+ or IHC 2+/FISH positive. NCT00073528.	19786658
GIMR	2021-09-20	FL	1B	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab deruxtecan	Phase 3 DESTINY-Breast03: PFS was significantly longer in patients treated with trastuzumab deruxtecan (T-DXD, 25.1 months) vs trastuzumab emtansine (T-DM1, 7.2 months). Confirmed ORR: 79% (T-DXD) vs 34% (T-DM1). 	10.1016/j.annonc.2021.08.2087
GIMR	2020-05-12	FL	1B	ERBB2	Amplification; Overexpression	Breast cancer	Trastuzumab deruxtecan	TGA approved. FDA approved. Phase 2 trial NCT03248492 (N=184). DESTINY-Breast01: In patients with prior anti-HER2 therapies, the objective response rate (ORR) was 62%, with a median duration of response (DOR) of 14.8 months. The median overall survival (OS) was 29.1 months, with a median progression-free survival (PFS) of 19.4 months in patients with HER2-positive metastatic breast cancer who were previously treated with trastuzumab emtansine. HER2 positivity was defined as IHC 3+ or FISH positive.	31825192, 38092229
GIMR	2024-03-19	FL	1B	ERBB2+CD274	CD274:Protein expression and NOT ERBB2:Amplification and NOT ERBB2:Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Pembrolizumab + Fluorouracil + Cisplatin; Pembrolizumab + Capecitabine + Oxaliplatin	Not PBS listed. TGA approved without biomarker. Phase 3. KEYNOTE-859. NCT03675737. N=1579. Pembrolizumab + chemotherapy significantly improved OS over chemotherapy alone in HER2-negative gastric or gastro-esophageal junction adenocarcinoma. In subgroup analysis, OS (versus placebo) was longer in PD-L1 CPS >= 1 and >= 10 subgroups but not in the <1 subgroup.	37875143
GIMR	2020-05-12	FL	1B	FGFR2	Fusions, FGFR2-ACLY fusion, FGFR2-AFF4 fusion, FGFR2-AHCYL1 fusion, FGFR2-ARHGAP22 fusion, FGFR2-ARHGAP24 fusion, FGFR2-ATAD2 fusion, FGFR2-ATF2 fusion, FGFR2-BICC1 fusion, FGFR2-BICD1 fusion, FGFR2-CCDC158 fusion, FGFR2-CCDC170 fusion, FGFR2-CCDC6 fusion, FGFR2-CEP128 fusion, FGFR2-COL16A1 fusion, FGFR2-CTNNA3 fusion, FGFR2-DBP fusion, FGFR2-DNAJC12 fusion, FGFR2-EEA1 fusion, FGFR2-EIF4ENIF1 fusion, FGFR2-FILIP1 fusion, FGFR2-GAB2 fusion, FGFR2-GOPC fusion, FGFR2-INSC fusion, FGFR2-KCTD1 fusion, FGFR2-KIAA1217 fusion, FGFR2-KIAA1598 fusion, FGFR2-LAMC1 fusion, FGFR2-MACF1 fusion, FGFR2-MATR3 fusion, FGFR2-MCU fusion, FGFR2-NEDD4L fusion, FGFR2-NOL4 fusion, FGFR2-NRAP fusion, FGFR2-NRBF2 fusion, FGFR2-PAH fusion, FGFR2-PAWR fusion, FGFR2-POC1B fusion, FGFR2-PXN fusion, FGFR2-RABGAP1L fusion, FGFR2-RASSF4 fusion, FGFR2-RPAP3 fusion, FGFR2-SFI1 fusion, FGFR2-SHROOM3 fusion, FGFR2-SLMAP fusion, FGFR2-SOGA1 fusion, FGFR2-SPICE1 fusion, FGFR2-STRN4 fusion, FGFR2-TACC1 fusion, FGFR2-TFEC fusion, FGFR2-TRIM8 fusion, FGFR2-TTC28 fusion, FGFR2-TXLNB fusion, FGFR2-USH2A fusion, FGFR2-VCL fusion, FGFR2-WAC fusion, FGFR2-WDHD1 fusion, FGFR2-ZMYM4 fusion	Cholangiocarcinoma	Pemigatinib	TGA approved. Not PBS reimbused. Phase 2 FIGHT-202 trial. NCT02924376. N=146. Pemigatinib showed an objective response in 35.5% of patients with FGFR2 fusions or rearrangements, with a median follow-up of 17.8 months.	32203698
GIMR	2020-05-07	FL/XT	1B	IDH2	R140Q, R140, R172K, R172S	Acute myeloid leukaemia	Enasidenib	TGA approved. Not PBS reimbursed. Phase 1/2 trial. NCT01915498. Enasidenib induced hematologic responses in relapsed/refractory AML patients with mutant IDH2, with an overall response rate of 40.3% and median overall survival of 9.3 months, and was generally well tolerated with grade 3 to 4 adverse events including indirect hyperbilirubinemia and IDH-inhibitor-associated differentiation syndrome.	28588020
GIMR	2020-06-15	FL	1B	JAK2	V617F	Polycythemia vera	Ruxolitinib	Phase 3. NCT01243944. Ruxolitinib demonstrated superiority to standard therapy in patients with polycythemia vera experiencing hydroxyurea inadequacy or intolerance, with significant improvements in hematocrit control (60% vs 20%), spleen volume reduction (38% vs 1%), and symptom management (49% vs 5%).	25629741
GIMR	2020-05-07	FL	1B	KIT	Protein expression	Gastrointestinal stromal tumour	Regorafenib	PBS reimbursed based on CD117 (c-KIT) IHC. Phase 3 GRID trial. NCT01271712. N=199. Regorafenib significantly improved PFS (4.8 months vs 0.9 months) compared to placebo in patients with metastatic GIST after failure of imatinib and sunitinib.	23177515
GIMR	2020-04-16	FL	1B	KRAS	G12C	Non-small cell lung cancer	Sotorasib	TGA provisional approval. Not PBS reimbursed. FDA approved for second-line and beyond. Phase 2 CODEBREAK100. Previously treated patients. ORR 37%. PFS 6.8mo. OS 12.5mo.	32955176, 34096690, 10.1016/j.jtho.2019.09.020, 10.1200/JCO.2021.39.15_suppl.9003
GIMR	2020-05-20	FL	1B	MET	Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	Tepotinib	TGA approved. FDA approved. VISION trial. NCT02864992. N=152. Detection of MET exon14 skipping mutation was performed on either liquid biopsy or biospy of the archival tumour tissue. Across all lines of therapy in the efficacy population (N=99), ORR was 48% in the liquid-biopsy group and 50% in the tissue-biopsy group. Molecular cfDNA response to tepotinib was defined as complete response at least 75% of depletion of cfDNA. 	32469185, 10.1016/j.jtho.2018.08.299
GIMR	2025-05-26	FL	1B	Microsatellite Instability	High	Colorectal adenocarcinoma	Nivolumab + Ipilimumab	TGA approved. Not PBS reimbursed. FDA approved. Phase 3 CheckMate 8HW trial. NCT04008030. Nivolumab plus ipilimumab significantly improved PFS over chemotherapy (24-month PFS 72% vs 14%) in patients with MSI-H or dMMR metastatic colorectal cancer who had not previously received systemic treatment for metastatic disease.	39602630
GIMR	2020-12-11	FL	1B	Microsatellite Instability	High	Colorectal adenocarcinoma	Pembrolizumab	TGA approved. KEYNOTE-177: First-line treatment for metastatic CRC. PFS v chemotherapy: 16.5 vs. 8.2 months. Note in KRAS-mutant subgroup, PFS in the pembrolizumab arm was not significantly different from the chemotherapy arm. MSI-H is defined as PCR-based analysis of 3-5 tumor microsatellite loci by local testing.	33264544, 10.1200/JCO.2020.38.18_suppl.LBA4
GIMR	2020-12-10	FL	1B	Microsatellite Instability	High	Colorectal adenocarcinoma	Pembrolizumab	TGA approved. KEYNOTE-164: In previously treated metastatic colorectal cancer, ORR was 33% and median OS was 31.4mo. MSI-H is defined as PCR-based analysis of microsatellite loci by local testing. 	31725351
GIMR	2020-12-10	FL	1B	Microsatellite Instability	High	Solid tumours	Pembrolizumab	TGA provisional approval for MSI-H/dMMR. FDA approved	26028255, 31682550, 10.1158/1078-0432.CCR-18-4070
GIMR	2025-05-26	FL	1B	Mismatch repair	Deficient	Colorectal adenocarcinoma	Nivolumab + Ipilimumab	TGA approved. Not PBS reimbursed. FDA approved. Phase 3 CheckMate 8HW trial. NCT04008030. Nivolumab plus ipilimumab significantly improved PFS over chemotherapy (24-month PFS 72% vs 14%) in patients with MSI-H or dMMR metastatic colorectal cancer who had not previously received systemic treatment for metastatic disease.	39602630
GIMR	2020-12-10	FL	1B	Mismatch repair	Deficient	Solid tumours	Pembrolizumab	TGA provisional approval for MSI-H/dMMR. FDA approved. ORR 34%. KEYNOTE-158: Median PFS 4.1months. Median OS 23.5 months.	26028255, 31682550, 10.1158/1078-0432.CCR-18-4070
GIMR	2025-07-30	FL	1B	NECTIN4	Protein expression	Urothelial carcinoma	Enfortumab vedotin + Pembrolizumab	Not PBS listed. TGA approved for first line therapy with Pembrolizumab. Phase 3 EV-302 trial. NCT04223856. N=886. Enfortumab vedotin + pembrolizumab significantly prolonged PFS (12.5 vs 6.3 months; HR 0.45) and OS (31.5 vs 16.1 months; HR 0.47) versus platinum-based chemotherapy in untreated advanced urothelial cancer. Nectin-4 is constitutively expressed in urothelial carcinoma and biomarker selection is not required. PD-L1 does not have differential predictive effect on therapy outcomes.	38446675
GIMR	2020-11-10	FL	1B	NTRK1	Fusions, CD74-NTRK1 fusion, CDC42BPA-NTRK1 fusion, CGN-NTRK1 fusion, EPS15L1-NTRK1 fusion, ERC1-NTRK1 fusion, LMNA-NTRK1 fusion, PDIA3-NTRK1 fusion, PEAR1- NTRK1 fusion, PLEKHA6-NTRK1 fusion, SQSTM1-NTRK1 fusion, TPM3-NTRK1 fusion, TPR-NTRK1 fusion, TRIM33-NTRK1 fusion	Solid tumours	Entrectinib	TGA approved. Not PBS reimbursed. ALKA-372-001, STARTRK-1, and STARTRK-2 trials.	31838007
GIMR	2020-11-10	FL	1B	NTRK2	Fusions, SQSTM1-NTRK2 fusion	Solid tumours	Entrectinib	TGA approved. Not PBS reimbursed. ALKA-372-001, STARTRK-1, and STARTRK-2 trials.	31838007
GIMR	2020-11-10	FL	1B	NTRK3	Fusions, AKAP13-NTRK3 fusion, EML4-NTRK3 fusion, ETV6-NTRK3 fusion, FAM19A2-NTRK3 fusion, KIF7-NTRK3 fusion, RBPMS-NTRK3 fusion	Solid tumours	Entrectinib	TGA approved. Not PBS reimbursed. ALKA-372-001, STARTRK-1, and STARTRK-2 trials.	31838007
GIMR	2020-04-16	FL	1B	PDGFRA	FIP1L1-PDGFRA Fusion; Fusion	Myelodysplastic/myeloproliferative diseases	Imatinib	TGA approved. Not PBS reimbursed. Multicenter prospective study. NCT00276929. Imatinib mesylate achieved complete hematologic remission in 27 FIP1L1-PDGFRalpha-positive hypereosinophilic syndrome patients, with durable responses at 100-400 mg daily, and treatment discontinuation led to rapid reappearance of fusion transcript.	17666373, 12047970
GIMR	2020-05-21	FL	1B	PDGFRA	Oncogenic mutations	Gastrointestinal stromal tumour	Ripretinib	TGA approved; FDA approved; Note PDGFRA was specified group in original trial, but only 3 cases were included in INVICTUS.	32511981, 32804590
GIMR	2020-04-16	FL	1B	PDGFRB	Fusions	Myelodysplastic/myeloproliferative diseases	Imatinib	TGA approved. Not PBS reimbursed. Retrospective cohort study. N=26. Patients with myeloid malignancies bearing PDGFRB fusion genes treated with imatinib had a 10-year overall survival rate of 90% and 6-year progression-free survival rate of 88% with 96% response rate.	24687085
GIMR	2020-04-16	FL	1B	PIK3CA	Oncogenic mutations, C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y	Breast cancer	Fulvestrant + Alpelisib	TGA approved. Not PBS reimbursed. SOLAR-1 trial.	31091374
GIMR	2021-06-21	FL	1B	PSMA	Protein expression	Prostate cancer	Lu-177 vipivotide tetraxetan	TGA approved. FDA approved 2022-03-24. Phase 3 VISION trial. NCT03511664. N=831. Lutetium-177-PSMA-617 plus standard care significantly prolonged PFS (8.7 vs 3.4 months, HR 0.40) and OS (15.3 vs 11.3 months, HR 0.62) in patients with PSMA-positive (Gallium-68 positive) metastatic castration-resistant prostate cancer.	34161051, 10.1200/JCO.2021.39.15_suppl.LBA4
GIMR	2020-06-15	FL	1B	SLAMF7	Protein expression	Multiple myeloma	Elotuzumab + Lenalidomide + Dexamethasone	TGA approved. Not PBS reimbursed. Phase 3 ELOQUENT-2 trial. NCT01239797. N=646. Elotuzumab + lenalidomide + dexamethasone significantly improved PFS (19.4 vs 14.9 months) and ORR (79% vs 66%) compared to lenalidomide + dexamethasone alone in patients with relapsed or refractory multiple myeloma.	26035255
GIMR	2020-09-25	FL	1B	Tumour Mutational Burden	High	Cervical cancer; Endometrial cancer; Neuroendocrine tumour; Salivary gland cancers; Small-cell lung cancer; Thyroid cancer; Vulvar cancer	Pembrolizumab	TGA provisionally approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H). TMB cut-off at 10mut/MB.	32919526
GIMR	2020-11-26	FL	1B	Tumour Mutational Burden	High	Non-small cell lung cancer	Nivolumab + Ipilimumab	TGA provisionally approved. Phase 3 CHECKMATE227 trial. Nivolumab + Ipilimumab significantly improved PFS (7.2 vs 5.5 months) and ORR (45.3% vs 26.9%) compared to chemotherapy in NSCLC patients with high TMB (≥10 mut/MB). Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort but outcomes not correlated with TMB.	29658845
GIMR	2020-12-11	FL	2	ABL1	BCR-ABL1 Fusion	Acute lymphoblastic leukaemia	Dasatinib + Blinatumomab	Phase 2 GIMEMA LAL2116 D-ALBA trial. N=63. CR rate 98%. Molecular response rate increased from 29% after dasatinib induction to 60% after 2 cycles of blinatumomab. At 18 months, OS was 95% and DFS was 88%.	33085860
GIMR	2020-05-21	FL	2	ABL1	BCR-ABL1 Fusion	Acute lymphoblastic leukaemia	Nilotinib	Not TGA approved for ALL; Phase 1 dose-escalation study. NCT00109707. N=119. Nilotinib showed activity in imatinib-resistant CML with hematologic and cytogenetic responses observed across various disease phases, and had a relatively favorable safety profile.	16775235
GIMR	2025-07-30	FL	2	ABL1	BCR-ABL1 Fusion	Chronic myelogenous leukaemia	Asciminib	Phase 3. ASC4FIRST. NCT04971226. N=405. Asciminib achieved a significantly higher major molecular response (MMR) at week 48 (67.7%) vs investigator-selected TKIs (49.0%; difference 18.9%) and vs imatinib (69.3% vs 40.2%; difference 29.6%) in newly diagnosed CML.	38820078
GIMR	2023-11-29	FL	2	AKT1	Oncogenic mutation	Breast cancer	Capivasertib + Fulvestrant	Not TGA approved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy.	37256976
GIMR	2021-09-03	FL	2	ALK	Fusion	Non-small cell lung cancer	Ensartinib	Not TGA approved. TGA approved. Phase 3 trial. eXalt3. NCT02767804. Ensartinib showed superior efficacy to crizotinib with significantly longer median PFS (25.8 vs 12.7 months) in the first-line metastatic setting and higher intracranial response rate (63.6% vs 21.1%) in patients with ALK-positive NSCLC.	34473194
GIMR	2020-04-25	FL	2	ALK	Fusions, EML4-ALK Fusion	Anaplastic large cell lymphoma 	Crizotinib	Not TGA approved. FDA approved. Phase 1b PROFILE 1013 study. NCT01121588. N=44. demonstrated crizotinib's durable activity in ALK-positive lymphomas (ORR 53%, 8 CRs, 1 PR, 2-year PFS 63%) and inflammatory myofibroblastic tumors (ORR 67%, 1 CR, 5 PRs, 2-year PFS 67%).	28032129, 29352732
GIMR	2020-04-16	FL	2	ALK	Fusions, RANBP2-ALK Fusion	Inflammatory myofibroblastic tumour	Crizotinib	Not TGA approved. FDA approved 14/7/2022. Sustained partial response observed in a patient with ALK-translocated inflammatory myofibroblastic tumor (IMT) treated with crizotinib, whereas no activity was seen in a patient without ALK translocation.	20979472
GIMR	2023-03-25	FL	2	APC	Oncogenic mutations	Aggressive fibromatosis	Nirogacestat	Not TGA approved. FDA approved 27/11/2023. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.	36884323
GIMR	2022-06-20	FL	2	BRAF	V600	High-grade gliomas	Dabrafenib + Trametinib	NCT02684058. Phase 2. Paediatric relapsed/refractory high-grade glioma. ORR was 56%, with median PFS of 9.0 months and DOR of 22.2 months.	37643378, 10.1200/JCO.2022.40.16_suppl.2009
GIMR	2022-06-24	FL	2	BRAF	V600	Low-grade gliomas	Dabrafenib + Trametinib	Not TGA approved. FDA approved 23/06/2022. Study X2101. NCT02124772. In paediatric glioma, treatment with dabrafenib and trametinib combination resulted in ORR of 25%.	10.1200/JCO.2020.38.15_suppl.10506
GIMR	2021-06-20	FL	2	BRAF	V600	Low-grade gliomas	Dabrafenib + Trametinib	Randomised phase 2. NCT02684058. In paediatric low-grade glioma, ORR was 47% (vs chemotherapy 11%) in the first-line setting. CBR 86% (vs chemotherapy 46%). Median PFS 20.1 (vs chemotherapy 7.4 months).	37733309, 10.1200/JCO.2022.40.17_suppl.LBA2002
GIMR	2022-04-09	FL	2	BRAF	V600	Melanoma	Atezolizumab + Vemurafenib + Cobimetinib	Not TGA approved. FDA approved. Phase 3 IMspire150. PFS is significantly prolonged versus control (15.1 vs 10.6 months) in the Atezolizumab arm.	32534646
GIMR	2024-04-26	FL	2	BRAF	V600, V600E, KIAA1549-BRAF fusion,Fusion	Low-grade gliomas	Tovorafenib	Not TGA approved. FDA approved. Phase 2. FIREFLY-1. PNOC026. n=77. BRAF-altered, relapsed/refractory pediatric low-grade glioma. The primary endpoint was met: ORR was 46/69 (67%) by RANO-HGG criteria. DOR was 16.6 months. 	37978284
GIMR	2023-05-09	FL	2	BRAF	V600E	Anaplastic thyroid cancer; Biliary tract cancer; Small intestine adenocarcinoma; Low-grade glioma; High-grade glioma; Hairy cell leukaemia; Multiple myeloma	Dabrafenib + Trametinib	Phase 2 basket trial. ROAR. NCT02034110. Rare cancer cohort. ORR was 56% for anaplastic thyroid carcinoma (PFS 6.7 months), 53% for biliary tract cancer (PFS 9.0 months), 67% for small intestine adenocarcinoma, 54% for low-grade glioma (PFS 9.5 months), 33% for high-grade glioma (PFS 5.5 months), 89% for hairy cell leukemia, and 50% for multiple myeloma (PFS 6.3 months).	37059834
GIMR	2020-09-21	FL	2	BRAF	V600E	Biliary tract cancers	Dabrafenib + Trametinib	Not TGA approved. Note FDA approval for tumour agnostic indication 23/06/2022. Phase 2 ROAR trial. NCT02034110. N=43. Dabrafenib plus trametinib showed activity in BRAF(V600E)-mutated biliary tract cancer with BICR ORR 47% and manageable safety profile.	32818466
GIMR	2020-04-16	FL	2	BRAF	V600E	Colorectal adenocarcinoma	Binimetinib + Encorafenib + Cetuximab	Not TGA approved. Triplet OS 9.3 months. Doublet recommended.	31566309, 33503393
GIMR	2025-03-22	FL	2	BRAF	V600E	Colorectal adenocarcinoma	Encorafenib + Cetuximab + FOLFOX	TGA approved. PBS reimbursed. Phase 3 BREAKWATER trial. NCT04607421. Patients with untreated BRAF V600E-mutated metastatic colorectal cancer. EC+mFOLFOX6 showed significantly longer PFS (12.8 vs 7.1 months) and OS (30.3 vs 15.1 months) compared to standard care. Updated 2025-05-31.	40444708, 39863775, 10.1200/JCO.2025.43.16_suppl.LBA3500
GIMR	2020-05-15	FL	2	BRAF	V600E	Erdheim-Chester disease; Langerhans Cell Histiocytosis	Vemurafenib	Not TGA approved. Not PBS reimbursed. FDA approved. Secondary analysis of VE-BASKET study showed 62% confirmed ORR by RECIST and 100% PET response arte. PFS rate at 2 year was 86%.	26287849, 29188284
GIMR	2020-04-16	FL	2	BRAF	V600E	Follicular thyroid cancer; Medullary thyroid cancer	Vemurafenib; Dabrafenib	Not TGA approved; NCCN recommended	NCCN:thyroid
GIMR	2022-04-07	FL	2	BRAF	V600E	Glioblastoma; High-grade glioma; Low-grade glioma	Dabrafenib + Trametinib	Not TGA approved. Phase 2. ROAR. NCT02034110. Dabrafenib plus trametinib showed ORR of 33% (15/45) in high-grade glioma (32% in glioblastoma) and 69% (9/13) in low-grade glioma, with a safety profile consistent with other indications.	34838156
GIMR	2021-12-07	FL	2	BRAF	V600E	Gliomas; High-grade gliomas; Low-grade gliomas	Dabrafenib + Trametinib	Not TGA approved. FDA approved 23/6/22. Phase 2. NCT02034110. In high-grade gliomas: ORR 33% (15/45), including 3 CR. Median PFS 3.8 months. Median OS 17.6 months. In low-grade gliomas: ORR 69% (9/13), including 1 CR. Median PFS and OS not reached.	34838156
GIMR	2020-05-15	FL	2	BRAF	V600E	Hairy cell leukaemia	Vemurafenib	Retrospective analysis of 21 HCL patients treated with vemurafenib showed 40% complete remission rate, and median event-free survival of 17 months, with response rate and kinetics independent of dosing.	26941398
GIMR	2020-07-31	FL	2	BRAF	V600E	Melanoma	Atezolizumab + Cobimetinib + Vemurafenib	Not TGA approved. Phase 3 IMspire150 trial. NCT02908672. N=514. Atezolizumab + vemurafenib + cobimetinib significantly improved PFS (15.1 vs 10.6 months; HR 0.78) compared to placebo + vemurafenib + cobimetinib in BRAF(V600) mutation-positive advanced melanoma patients.	31171876, 32534646
GIMR	2023-10-17	FL	2	BRAF	V600E	Non-small cell lung cancer	Encorafenib + Binimetinib	Not TGA approved. FDA approved. Phase 2, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer. NCT03148795. PHAROS. N=98. ORR was 75% (treatment naive) and 46% (previously treated). DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE in treatment-naïve and 9.3 months in previously treated patients. Median OS 47.6 months in treatment-naive patients; 4-year OS probability 49%. Median OS 22.7 months in previously treated patients; 4-year OS probability 31%. Median duration of treatment 16.3 months (naive) and 5.5 months (treated).	37270692, 41109959
GIMR	2020-12-30	FL	2	BRAF	V600E	Solid tumours except Colorectal adenocarcinoma, melanoma, thyroid cancer	Dabrafenib + Trametinib	Not TGA approved. FDA approved 23/6/2022. NCI-MATCH Trial Subprotocol H. N=23. ORR 38%. Colorectal cancer, melanoma, thyroid cancers were excluded.	32758030
GIMR	2020-04-16	FL	2	BRAF	V600E, N486_T491del	Histiocytosis	Cobimetinib	Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations.	30867592
GIMR	2022-06-06	FL	2	BRCA1	Oncogenic mutations	Ovarian cancer	Rucaparib	Phase 3. NCT03522246. ATHENA-MONO. In advanced epithelial ovarian cancer, In HRD population, PFS was significantly prolonged in Rucaparib arm over placebo (28.7 v 11.3 months). Note PFS was also significantly prolonged in ITT population (20.2 v 9.2 months).	35658487
GIMR	2023-10-23	FL	2	BRCA1	Oncogenic mutations	Prostate cancer	Enzalutamide + Talazoparib	Not TGA approved. Phase 3 TALAPRO-2 trial. NCT03395197. N=805. Talazoparib plus enzalutamide significantly improved rPFS over placebo (not reached versus 21.9 months) in the first-line castrate-resistant setting. The benefit was observed in both HRR deficient and non-deficent groups, although significant higher HR reduction was seen in the BRCA1/2 deficient subgroup treated with Enzalutamide + Talazoparib.	37285865
GIMR	2023-03-29	FL	2	BRCA1	Oncogenic mutations	Prostate cancer	Niraparib + Abiraterone Acetate	Phase 3. MAGNITUDE. NCT03748641. First-line metastatic prostate cancer. In the BRCA1/2 subgroup, median radiological PFS was longer in the niraparib + abiraterone group compared to abiraterone alone (16.6 v 10.9 months). In contrast, non-BRCA1/2 but HR-positive group (comprising ATM, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) did not show prolonged radiologic PFS (HR 0.99).	36952634
GIMR	2020-05-20	FL	2	BRCA1	Oncogenic mutations	Prostate cancer	Rucaparib	Not TGA Approved. Phase 2 TRITON2 study. Rucaparib showed antitumor activity in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration, with confirmed ORR of 43.5% and PSA response rate of 54.8%.	32795228, 10.1093/annonc/mdy284.002
GIMR	2021-12-21	FL	2	BRCA1	Oncogenic mutations (germline)	Ovarian cancer	Pamiparib	Phase 2. NCT03333915. In Chinese patients with advanced ovarian cancer that harbour BRCA mutations, pamiparib achieved ORR of 65% in platinum-sensitive disease (cohort 1, 53/82, including 8 CR) and 32% (cohort 2, 6/19) in platinum-resistant disease. PFS were 15.2 (cohort 1) months and 6.2 (cohort 2) months respectively. Approved in China April 2021.	10.1016/j.annonc.2020.08.959, 34844979
GIMR	2020-09-03	FL	2	BRCA1	Oncogenic mutations (germline)	Triple-negative breast cancer	Veliparib + Carboplatin + Paclitaxel	Not TGA approved. Phase 3 BROCADE3 trial. NCT02163694. N=509. Median PFS was significantly longer in patients receiving veliparib with carboplatin-paclitaxel versus placebo (14.5 months vs 12.6 months) with a HR of 0.71 in patients with germline BRCA mutation-associated advanced HER2-negative breast cancer.	32861273
GIMR	2022-04-09	FL	2	BRCA1	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Rucaparib	Not TGA approved. NCT02855944. ARIEL4. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5·7 months), including both platinum sensitive and resistant populations. Note, Rucaparib did not improve OS over chemotherapy (19.4 versus 25.4 months) in BRCA1/2-mutated relapsed ovarian cancer. 69% of patients in chemotherapy group crossed over to receive rucaparib.	35298906, 39914419
GIMR	2020-05-31	FL	2	BRCA1	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Veliparib	Not TGA approved. Phase 3 trial. VELIA/GOG-3005. NCT02470585. N=1140. Veliparib added to carboplatin and paclitaxel induction therapy followed by veliparib maintenance significantly improved PFS in BRCA-mutation cohort (34.7 vs 22.0 months), HRD cohort (31.9 vs 20.5 months), and intention-to-treat population (23.5 vs 17.3 months).	31562800
GIMR	2020-04-27	FL	2	BRCA1	Oncogenic mutations, Oncogenic mutations (germline), M1V, M1I, C61G, C64Y, R71G, R71K, R1495M, E1559K, D1692N, D1692H, R1699W, A1708E, G1788V	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Rucaparib	Not TGA approved. Phase 3 ARIEL3 trial. NCT01968213. N=564. Rucaparib maintenance treatment significantly improved PFS in patients with platinum-sensitive ovarian cancer, with median PFS of 16.6 months vs 5.4 months in BRCA-mutant carcinoma, 13.6 months vs 5.4 months in homologous recombination deficient carcinoma, and 10.8 months vs 5.4 months in the intention-to-treat population. Both germline and somatic BRCA1/2 mutations are included.	28916367
GIMR	2026-03-03	FL	2	BRCA1+ERBB2	BRCA1:Oncogenic mutations (germline) AND NOT ERBB2:Amplification AND NOT ERBB2:Overexpression	Breast cancer	Fuzuloparib + Apatinib	Phase 3 FABULOUS trial. NCT04296370. N=203. Fuzuloparib with apatinib significantly improved PFS (11.0 months) compared to fuzuloparib alone (6.7 months) and chemotherapy (3.0 months) in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations. Fuzuloparib-apatinib HR 0.27, p<0.0001; fuzuloparib HR 0.49, p=0.0004. 	41308673
GIMR	2022-06-06	FL	2	BRCA2	Oncogenic mutations	Ovarian cancer	Rucaparib	Phase 3. NCT03522246. ATHENA-MONO. In advanced epithelial ovarian cancer, In HRD population, PFS was significantly prolonged in Rucaparib arm over placebo (28.7 v 11.3 months). Note PFS was also significantly prolonged in ITT population (20.2 v 9.2 months).	35658487
GIMR	2023-10-23	FL	2	BRCA2	Oncogenic mutations	Prostate cancer	Enzalutamide + Talazoparib	NOT TGA approved. Phase 3 TALAPRO-2 trial. NCT03395197. N=805. Talazoparib plus enzalutamide significantly improved rPFS over placebo (not reached versus 21.9 months)  in the first-line castrate-resistant setting. The benefit was observed in both HRR deficient and non-deficent groups, although significant higher HR reduction was seen in the BRCA1/2 deficient subgroup treated with Enzalutamide + Talazoparib.	37285865
GIMR	2023-03-29	FL	2	BRCA2	Oncogenic mutations	Prostate cancer	Niraparib + Abiraterone Acetate	Phase 3. MAGNITUDE. NCT03748641. First-line metastatic prostate cancer. In the BRCA1/2 subgroup, median radiological PFS was longer in the niraparib + abiraterone group compared to abiraterone alone (16.6 v 10.9 months). In contrast, non-BRCA1/2 but HR-positive group (comprising ATM, BRIP1, CDK12, CHEK2, FANCA, HDAC2, PALB2) did not show prolonged radiologic PFS (HR 0.99).	36952634
GIMR	2020-05-20	FL	2	BRCA2	Oncogenic mutations	Prostate cancer	Rucaparib	Not TGA Approved. Phase 2 TRITON2 study. Rucaparib showed antitumor activity in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration, with confirmed ORR of 43.5% and PSA response rate of 54.8%.	32795228, 10.1093/annonc/mdy284.002
GIMR	2021-12-21	FL	2	BRCA2	Oncogenic mutations (germline)	Ovarian cancer	Pamiparib	Phase 2. NCT03333915. In Chinese patients with advanced ovarian cancer that harbour BRCA mutations, pamiparib achieved ORR of 65% in platinum-sensitive disease (cohort 1, 53/82) and 32% (cohort 2, 6/19) in platinum-resistant disease. PFS were 15.2 (cohort 1) months and 6.2 (cohort 2) months respectively. Approved in China April 2021.	10.1016/j.annonc.2020.08.959, 34844979
GIMR	2020-09-03	FL	2	BRCA2	Oncogenic mutations (germline)	Triple-negative breast cancer	Veliparib + Carboplatin + Paclitaxel	Not TGA approved. Phase 3 BROCADE3 trial. NCT02163694. N=509. Median PFS was significantly longer in patients receiving veliparib with carboplatin-paclitaxel versus placebo (14.5 months vs 12.6 months) with a HR of 0.71 in patients with germline BRCA mutation-associated advanced HER2-negative breast cancer.	32861273
GIMR	2022-04-09	FL	2	BRCA2	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Rucaparib	Not TGA approved. NCT02855944. ARIEL4. Median PFS was significantly longer in rucaparib group than chemotherapy group (7.4 versus 5·7 months), including both platinum sensitive and resistant populations. Note, Rucaparib did not improve OS over chemotherapy (19.4 versus 25.4 months) in BRCA1/2-mutated relapsed ovarian cancer. 69% of patients in chemotherapy group crossed over to receive rucaparib.	35298906, 39914419
GIMR	2020-05-31	FL	2	BRCA2	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Veliparib	Not TGA approved. Phase 3 trial. VELIA/GOG-3005. NCT02470585. N=1140. Veliparib added to carboplatin and paclitaxel induction therapy followed by veliparib maintenance significantly improved PFS in BRCA-mutation cohort (34.7 vs 22.0 months), HRD cohort (31.9 vs 20.5 months), and intention-to-treat population (23.5 vs 17.3 months).	31562800
GIMR	2020-04-27	FL	2	BRCA2	Oncogenic mutations, Oncogenic mutations (germline), M1R, M1I, V159M, V211L, V211I, R2336P, R2336H	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Rucaparib	Not TGA approved. Phase 3 ARIEL3 trial. NCT01968213. N=564. Rucaparib maintenance treatment significantly improved PFS in patients with platinum-sensitive ovarian cancer, with median PFS of 16.6 months vs 5.4 months in BRCA-mutant carcinoma, 13.6 months vs 5.4 months in homologous recombination deficient carcinoma, and 10.8 months vs 5.4 months in the intention-to-treat population. Both germline and somatic BRCA1/2 mutations are included.	28916367
GIMR	2026-03-03	FL	2	BRCA2+ERBB2	BRCA2:Oncogenic mutations (germline) AND NOT ERBB2:Amplification AND NOT ERBB2:Overexpression	Breast cancer	Fuzuloparib + Apatinib	Phase 3 FABULOUS trial. NCT04296370. N=203. Fuzuloparib with apatinib significantly improved PFS (11.0 months) compared to fuzuloparib alone (6.7 months) and chemotherapy (3.0 months) in patients with HER2-negative metastatic breast cancer with germline BRCA1/2 mutations. Fuzuloparib-apatinib HR 0.27, p<0.0001; fuzuloparib HR 0.49, p=0.0004. 	41308673
GIMR	2025-04-23	FL	2	CCL11	Serum level high	Pancreatic adenocarcinoma	GV1001 + Gemcitabine + Capecitabine	Phase 3. NCT02854072. N=148. GV1001 + gemcitabine/capecitabine improved OS (11.3 vs 7.5 months) and TTP (7.3 vs 4.5 months) in eotaxin-high patients with advanced PDAC.	37903909
GIMR	2020-06-15	FL	2	CD123	Overexpression	Blastic plasmacytoid dendritic cell neoplasm	Tagraxofusp-erzs	Phase 1/2 trial. NCT02113982. N=47. Tagraxofusp showed a combined rate of complete response and clinical complete response of 72% in previously untreated BPDCN patients, with an overall response rate of 90% and 45% proceeding to stem-cell transplantation.	31018069
GIMR	2020-06-15	FL	2	CD20	Protein expression	Chronic lymphocytic leukaemia	Ofatumumab	Phase 2 study. N=138. Ofatumumab demonstrated an ORR of 58% in fludarabine- and alemtuzumab-refractory CLL, and 47% in fludarabine-refractory CLL with bulky lymphadenopathy. Median PFS was 5.7-5.9 months, with OS of 13.7-15.4 months.	20194866
GIMR	2020-06-15	FL	2	CD20	Protein expression	Follicular lymphoma; Marginal zone lymphoma	Lenalidomide + Rituximab	Phase 2 trial. N=45. Previously untreated MZL patients treated with lenalidomide and rituximab showed ORR of 93% with 70% CR/CRu. Median PFS was 59.8 months and 5-year OS was 96% at median follow-up of 75.1 months.	30184451, 30919940
GIMR	2025-06-01	FL	2	CD274	Protein expression	Non-small cell lung cancer	Benmelstobart + Anlotinib	Phase 3. NCT04964479. In PD-L1 positive NSCLC patients, benmelstobart + anlotinib significantly improved PFS (11.0 vs 7.1 months) and ORR (57.3% vs 39.6%) compared to pembrolizumab, particularly in subgroups with squamous cell carcinoma and PD-L1 expression ≥50%.	10.1200/JCO.2025.43.16_suppl.LBA8502
GIMR	2021-02-24	FL	2	CD274	Protein expression	Non-small cell lung cancer	Cemiplimab	Not TGA approved. FDA Approved. EMPOWER-Lung 1: As first-line treatment, cemiplimab resulted in median PFS of 8.2 (vs 5.7 mo chemotherapy, HR 0.54) in patients with PD-L1 expression (Tumour proportion score) >= 50% as determined by the 22C3 PharmDx assay. EGFR, ALK, and ROS1 negative population. Duration and depth of response correlate to PD-L1 TPS.	33581821, 10.1016/j.annonc.2020.08.2285
GIMR	2022-02-21	FL	2	CD274	Protein expression	Oesophageal squamous cell carcinoma	Nivolumab + Ipilimumab; Nivolumab + Fluorouracil + Cisplatin	Not TGA approved. FDA approved. Phase 3. CHECKMATE-648. NCT03143153. In PD-L1 positive population (>=1%), the addition of nivolumab to chemotherapy had significant longer median OS (15.4 months, Nivolumab + chemotherapy) vs. 9.1 months (chemotherapy alone). The combination of nivolumab + Ipilimumab was also significantly longer (median OS: 13.7 months). compared with the chemotherapy arm, PFS was significantly longer in chemoimmunotherapy arm (6.9 versus 4.4 months) in the PD-L1 positive population, but not in the nivolumab + ipilimumab arm. No OS difference in either Nivolumab arm from chemotherapy was seen in PD-L1 <1% group. PD-L1 status was primarily stratified by using tumour-cell PD-L1 expression (Dako IHC 28-8 pharmDx assay).	35108470
POTTR	2020-04-16	FL	2	CD274	Protein expression	Oesophageal squamous cell carcinoma	Pembrolizumab	Not TGA approved. Not PBS reimbursed. KEYNOTE-181: superior OS in Pembrolizumab arm. PD-L1 positive (defined as CPS ≥ 10%), and overall groups.	33026938, 10.1200/JCO.2019.37.4_suppl.2
GIMR	2020-09-21	FL	2	CD274	Protein expression	Urothelial carcinoma	Avelumab	Not TGA approved. FDA Approved. JAVELIN Bladder 100: Maintenance therapy after response to first-line platinum therapy. PD-L1 status is determined by SP263 assay and is considered positive if >=25% TC positive, >=25% IC positive with >= 1% TC positive, or 100% IC if <1% TC positive. PFS 5.7 vs 2.1 months, and OS NE vs 17.1 months, in PD-L1 positive population (vs best supportive care). In PD-L1 negative group, there was also PFS benefit shown but no OS improvement over best supportive care.	32945632
GIMR	2026-03-03	FL	2	CD274+ESR1+ERBB2	NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and NOT CD274:protein expression	Triple-negative breast cancer	Sacituzumab Govitecan + Pembrolizumab	Phase 3 ASCENT-04/KEYNOTE-D19. NCT05382286. N=443. Sacituzumab Govitecan + Pembrolizumab significantly prolonged PFS over chemotherapy + Pembrolizumab (11.2 vs 7.8 months) in previously untreated PD-L1–positive advanced TNBC. Objective response rate was 60% vs 53%; median DOR 16.5 vs 9.2 months.	41564397
GIMR	2020-06-15	FL	2	CD38	Overexpression	Multiple myeloma	Daratumumab + Hyaluronidase-fihj	Phase 3 COLUMBA trial. NCT03277105. Subcutaneous daratumumab was non-inferior to intravenous daratumumab in terms of overall response (41% vs 37%).	32213342
GIMR	2024-10-19	FL	2	CLDN18+ERBB2	CLDN18:Protein expression AND NOT ERBB2:Overexpression; CLDN18:Protein expression AND NOT ERBB2:Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma	Zolbetuximab + CAPOX	Not TGA approved. FDA approved. Phase 3 GLOW trial. NCT03653507. N=507. Zolbetuximab + CAPOX improved PFS over placebo (8.2 vs 6.8 months) and OS 14.4 vs 12.2 months in CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma. Claudin18.2 expression was defined as >= 75% of tumor cells with moderate-to-strong membranous staining on immunohistochemistry.	37524953
GIMR	2023-01-20	FL	2	CLDN18+ERBB2	CLDN18:Protein expression AND NOT ERBB2:Overexpression; CLDN18:Protein expression AND NOT ERBB2:Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma	Zolbetuximab + FOLFOX	Phase 3. SPOTLIGHT. NCT03504397. N=565. Addition of Zolbetuximab significantly prolonged both PFS and OS in previously untreated patients with Claudin 18.2 positive and HER2 negative gastric and gastroesophageal cancers (median PFS 10.6 vs 8.7 months, median OS 18.2 vs 15.5 months). CLDN18 positive was defined as moderate-to-strong IHC staining in >= 75% of tumour cells	37068504, 10.1200/JCO.2023.41.3_suppl.LBA292
GIMR	2021-12-29	FL	2	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Pexidartinib	FDA Approved. Phase 3. ENLIVEN. NCT02371369. ORR at week 25 Pexidartinib (39%) compared to placebo (0%). BOR was 53%. FDA approval 02/08/2019. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1.	31229240
GIMR	2025-05-26	FL	2	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Vimseltinib	FDA approved. Phase 3 MOTION trial. NCT05059262. N=123. Vimseltinib achieved a significant objective response rate of 40% compared to 0% with placebo (p<0.0001) in patients with tenosynovial giant cell tumour. Note that alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1.	38843860
GIMR	2023-03-25	FL	2	CTNNB1	Oncogenic mutations	Aggressive fibromatosis	Nirogacestat	Not TGA approved. FDA approved 27/11/2023. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.	36884323
GIMR	2026-03-03	FL	2	DLL3	Protein expression	Small-cell lung cancer	Tarlatamab	Phase 3. DeLLphi-304 trial. NCT05740566. N=509. Tarlatamab significantly improved OS (13.6 vs 8.3 months) and PFS compared to chemotherapy (topotecan, lurbinectedin, or amrubicin) in patients with small-cell lung cancer after platinum-based chemotherapy. Note DLL3 expression is not required for entry into the trial. Treatment outcome was not evaluated against DLL3 expression.	40454646
GIMR	2020-09-25	FL	2	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Apatinib + Gefitinib 	Apatinib not TGA or FDA approved. ACTIVE Phase 3 trial.	10.1016/j.annonc.2020.08.2283
GIMR	2022-12-14	FL	2	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Aumolertinib	Not TGA approved. EMA approved. AENEAS. Phase 3. NCT03849768. Median DOR of Aumolertinib was 18.1 months vs Gefitinib 8.3 months.	35580297
GIMR	2020-04-27	FL	2	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Dacomitinib	Not TGA approved. Phase 3 ARCHER 1050 and 1009 trials. Dacomitinib showed improved PFS over gefitinib (14.7 vs 9.2 months) in first-line EGFR-mutation-positive NSCLC, but not over erlotinib in previously treated NSCLC (2.6 months in both groups).	28958502, 25439691
GIMR	2023-07-18	FL	2	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Lazertinib	Phase 3 .LASER301 trial. N=393. In first-line EGFR-mutated NSCLC, Lazertinib showed significantly longer median PFS compared to gefitinib (20.6 vs 9.7 months, HR 0.45, 95% CI 0.34-0.58, P<0.001). PFS benefit observed across all predefined subgroups. ORR similar between Lazertinib versus Gefitinib. Median DOR longer with lazertinib (19.4 months vs 8.3 months). OS at 18-month was higher with lazertinib (80% vs 72%).	37379502
GIMR	2024-09-15	FL	2	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Furmonertinib	Phase 3. FURLONG trial. NCT03787992. N=358. Median PFS was significantly longer in patients treated with furmonertinib versus gefitinib (20.8 vs 11.1 months) as first-line therapy in EGFR mutation-positive NSCLC.	35662408
GIMR	2025-06-01	FL	2	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Sacituzumab tirumotecan	Phase 2/3 OptiTROP-Lung03 trial. NCT05631262. In EGFR-mutated NSCLC patients previously treated with EGFR TKI and platinum-based chemotherapy, sacituzumab tirumotecan demonstrated superior efficacy versus docetaxel with ORR of 45.1% vs 15.6%, PFS of 6.9 vs 2.8 months, and OS HR of 0.49.	10.1200/JCO.2025.43.16_suppl.8507
GIMR	2025-10-19	FL	2	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Sacituzumab tirumotecan	Phase 3. OptiTROP-Lung04 trial. (NCT05870319). N=376. 1:1 to sac-TMT versus pemetrexed + platinum chemotherapy in EGFR-mutated, EGFR-TKI-Resistant NSCLC with progression on EGFR-TKIs. Sac-TMT demonstrated significantly longer PFS (8.3 vs 4.3 months) and improved 18-month OS (65.8% vs 48.0%) compared to platinum-based chemotherapy. 	41124220, ESMO25.LBA5
GIMR	2021-03-07	FL	2	EGFR	Exon 20 insertion	Non-small cell lung cancer	Mobocertinib	Not TGA approved. FDA approved 2021-09-15. NCT02716116: Phase 1/2 trial. ORR to TAK-788 was 43% in 28 patients who had exon 20 insertion. Median DOR was 14 months. Median PFS was 7.3 months.	33632775
GIMR	2025-06-01	FL	2	EGFR	Exon 20 insertion	Non-small cell lung cancer	Zipalertinib	Phase 2b REZILIENT1 study. Zipalertinib achieved a confirmed ORR of 35% and median PFS of 9.5 months in non-small cell lung cancer patients harboring EGFR exon 20 insertion mutations following prior platinum-based chemotherapy with or without amivantamab.	40450572, 10.1200/JCO-25-00763, 10.1200/JCO.2025.43.16_suppl.8503
GIMR	2020-05-20	FL	2	EGFR	G719, L861Q, S768I	Non-small cell lung cancer	Erlotinib; Gefitinib	Intermediate response to first generation EGFR TKI; G719X mutation in NSCLC has an average response rate of 35.1% to TKIs, and other uncommon EGFR mutations such as exon 18 indels, exon 19 insertions, A763_Y764insFQEA, S768I, L861Q, kinase domain duplications, and rearrangements are also responsive to EGFR TKIs.	27413714, 28184913
GIMR	2025-06-01	FL	2	EGFR+MET	EGFR:Oncogenic mutations and MET:amplification	Non-small cell lung cancer	Savolitinib + Osimertinib 	Phase 3 SACHI study. In EGFR-mutant, MET-amplified advanced NSCLC patients progressing on EGFR-TKI, savolitinib + osimertinib significantly improved PFS versus chemotherapy (8.2 vs 4.5 months, HR=0.34). MET amplification was defined as copy number ≥5 or MET/CEP7 ratio ≥2.0.	10.1200/JCO.2025.43.17_suppl.LBA8505
GIMR	2020-05-04	FL	2	ERBB2	Amplification	Breast cancer	Lapatinib + Trastuzumab	Not TGA approved. Upon progression of trastuzumab-containing specimens.	20124187
GIMR	2020-05-17	FL	2	ERBB2	Amplification	Breast cancer	Neratinib + Capecitabine	Not TGA approved. FDA approved. NALA: Phase 3 trial in patient previously treated with two or more lines of HER2-directed regimens, median PFS of neratinib was superior over lapatinib.	10.1200/JCO.2019.37.15_suppl.1002
GIMR	2020-05-30	FL	2	ERBB2	Amplification	Breast cancer	Pyrotinib + Capecitabine	Not TGA approved. Phase 3 PHOEBE trial. NCT03080805. N=267. Pyrotinib plus capecitabine significantly improved PFS (12.5 months vs 6.8 months, HR 0.39) compared to lapatinib plus capecitabine in HER2-positive metastatic breast cancer patients previously treated with trastuzumab and taxanes.	33581774, 10.1200/JCO.2020.38.15_suppl.1003
GIMR	2026-03-04	FL	2	ERBB2	Amplification, Overexpression	Breast cancer	Eribulin + Trastuzumab + Pertuzumab	Phase 3 EMERALD trial. NCT03264547. N=446. Trastuzumab-pertuzumab plus eribulin noninferior to taxane in first-line HER2+ breast cancer. Median PFS 14.0 months versus 12.9 months (HR, 0.95 [95% CI, 0.76 to 1.19]). Median OS not reached versus 65.3 months in taxane group.	39787453
GIMR	2021-07-06	FL	2	ERBB2	Amplification, Overexpression	Breast cancer	Pyrotinib + Capecitabine	Phase 3. PHOEBE. Patients treated with pyrotinib with capecitabine had longer PFS (12.5 mo) vs Lapatinib and capacitabine (6.8 months) in HER2-positive breast cancers. HER2-positivity defined as IHC 3+ or amplification identified on FISH.	33581774
GIMR	2026-03-03	FL	2	ERBB2	Amplification, Overexpression	Breast cancer	Trastuzumab deruxtecan + Pertuzumab	Phase 3. DESTINY-Breast09 trial. NCT04784715. N=770. Trastuzumab deruxtecan plus pertuzumab significantly improved PFS (40.7 months) compared to taxane, trastuzumab, and pertuzumab (THP) (26.9 months) as first-line treatment for HER2-positive metastatic breast cancer. ORR was 85.1% with trastuzumab deruxtecan plus pertuzumab and 78.6% with THP. 	41160818
GIMR	2026-03-04	FL	2	ERBB2	Amplification, Overexpression	Breast cancer	Tucatinib + Trastuzumab + Pertuzumab	Phase 3. HER2CLIMB-05. NCT05132582. N=654. Tucatinib plus trastuzumab and pertuzumab versus placebo plus trastuzumab and pertuzumab as first-line maintenance therapy for HER2+ metastatic breast cancer. Investigator-assessed PFS significantly improved with tucatinib (24.9 v 16.3 months). PFS benefit observed regardless of brain metastasis presence or hormone receptor status. OS data immature.	41369677
GIMR	2022-08-26	FL	2	ERBB2	Amplification, Overexpression	Colorectal adenocarcinoma	Trastuzumab + Tucatinib	Not TGA approved. FDA approved 19/01/2023. Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=84 (Cohort A and B). In metastatic CRC after two-lines of systemic treatment, the tucatinib and trastuzumab combination resulted in ORR of 38% (Cohorts A + B). Median DOR was 12.4 months. Median PFS 8.2 months. Median OS was 24.1 months at follow-up of 20.7 months. 	37142372, 10.1016/j.annonc.2022.04.440
GIMR	2026-03-03	FL	2	ERBB2	Amplification, Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Trastuzumab deruxtecan	Phase 3. DESTINY-Gastric04 trial. NCT04704934. N=494. Trastuzumab deruxtecan significantly improved OS (14.7 vs 11.4 months) and PFS over ramucirumab plus paclitaxel in HER2-positive metastatic gastric cancer, ORR 44.3% vs 29.1%.	40454632
GIMR	2020-12-18	FL	2	ERBB2	Amplification; Overexpression	Breast cancer	Margetuximab + Capecitabine; Margetuximab + Eribulin; Margetuximab + Gemcitabine; Margetuximab + Vinorelbine	Not TGA approved. FDA approval for margetuximab and chemotherapy combination	10.1200/JCO.2019.37.15_suppl.1000
GIMR	2026-03-03	FL	2	ERBB2	Amplification; Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Zanidatamab + FOLFOX	Not TGA approved. FDA approved (accelerated). Phase 2 trial. NCT03929666. N=46. Zanidatamab plus chemotherapy showed a confirmed objective response rate of 76.2% with a median duration of response of 18.7 months in HER2-positive advanced gastro-oesophageal adenocarcinoma. Median PFS was 12.5 months and median OS was 36.5 months.	40473445
GIMR	2026-03-03	FL	2	ERBB2	Exon 20 insertions, A775_G776insYVMA, Oncogenic mutations, 	Non-small cell lung cancer	Sevabertinib	Phase 1-2 SOHO-01 trial, NCT05099172, N=209, Sevabertinib showed antitumor activity in HER2-mutant NSCLC patients with ORR of 64% (Cohort D), 38% (Cohort E), and 71% (Cohort F), with median PFS of 8.3 months, 5.5 months.	41104928
GIMR	2023-11-05	FL	2	ERBB2	Oncogenic mutation	Non-small cell lung cancer	Trastuzumab deruxtecan	Phase 2 trial. DESTINY-Lung02. NCT04961073. N=152. Dose optimization study. Confirmed ORR was 49% (Median DOR 16.8 months) and 56% (NE) in T-DXd 5.4mg/kg and 6.4 mg/kg respectively. Grade ≥3 treatment related adverse events occurred in 38.6% and 58% of patients receiving 5.4 and 6.4 mg/kg, respectively.	37694347
GIMR	2025-06-01	FL	2	ERBB2	Oncogenic mutations, Tyrosine kinase domain mutations	Non-small cell lung cancer	Sevabertinib	Phase 1/2 SOHO-01 trial. In patients with advanced HER2-mutant NSCLC, Sevabertinib demonstrated an ORR of 59% in both pretreated patients naive to HER2-targeted therapy and treatment-naive patients.	10.1200/JCO.2025.43.16_suppl.8504
GIMR	2023-06-20	FL	2	ERBB2	Overexpression	Biliary tract cancer	Trastuzumab deruxtecan	Not TGA approved. FDA approved (accelerated). Phase 2. NCT04482309. DESTINY-PanTumor02. N=267. Trastuzumab deruxtecan showed an ORR of 37.1% with a median DOR of 11.3 months, PFS of 6.9 months, and OS of 13.4 months in HER2-expressing solid tumors; greatest benefit was seen in the IHC 3+ population. In in biliary tract cancers, the ORR was 56% in the IHC 3+ group. No responses were seen in the IHC 2+ population.	37870536, 37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000
GIMR	2024-08-29	FL	2	ERBB2	Overexpression	Colorectal cancer	Trastuzumab deruxtecan	Not TGA approved. FDA approved. Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. Trastuzumab deruxtecan demonstrated an overall response rate (ORR) of 34% (42/122) across two dose groups. The ORR was higher in the HER2 IHC 3+ population (47%, 30/64) but lower in the HER2 IHC 2+ with amplified group (5.6%, 1/18).	39116902
GIMR	2020-01-15	FL	2	ERBB2	Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Trastuzumab deruxtecan	Not TGA approved. FDA approved. DESTINY-Gastric01. No response in patients with HER2 ISH+ and IHC 2+	32469182
GIMR	2024-11-01	FL	2	ERBB2	Overexpression, Amplification	Breast cancer	Trastuzumab duocarmazine	Phase 3. TULIP. NCT03262935. N=437. Trastuzumab duocarmazine improved PFS over physician's choice (7.0 vs 4.9 months) with HR of 0.64 in patients with HER2-positive advanced or metastatic breast cancer who progressed during/after 2 or more HER2-targeted therapies or after T-DM1.	39442070
GIMR	2025-06-01	FL	2	ERBB2	Overexpression, Amplification	Non-small cell lung cancer	Trastuzumab deruxtecan	Phase 3 DESTINY-Gastric04 trial. NCT04704934. In HER2+ (IHC 3+ or IHC 2+/ISH+) unresectable/metastatic GC/GEJA patients, T-DXd showed significant improvement in OS (14.7 vs 11.4 months), PFS (6.7 vs 5.6 months), and confirmed ORR (44% vs 29%) over Ramucirumab + Paclitaxel	10.1200/JCO.2025.43.16_suppl.LBA4002
GIMR	2023-06-20	FL	2	ERBB2	Overexpression, Protein expression	Cervical cancer; Endometrial cancer; Ovarian cancer; Bladder cancer; Solid tumours except Pancreatic adenocarcinoma, Biliary tract cancers	Trastuzumab deruxtecan	Phase 2. NCT04482309. DESTINY-PanTumor02 trial. N=267. Trastuzumab deruxtecan showed an ORR of 37% with a median DOR of 11.3 months, PFS of 6.9 months, and OS of 13.4 months in HER2-expressing solid tumors; greatest benefit was seen in the IHC 3+ population.	37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000
GIMR	2021-09-20	FL	2	ERBB2	Overexpression, Protein expression AND Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma	Trastuzumab deruxtecan	Phase 2. DESTINY-Gastric02: N=79. Single-arm trial of trastuzumab deruxtecan in patients previously treated with trastuzumab. ORR 38% (30/79).  Median PFS 5.5 months. Median DOR 8.1 months.	10.1016/annonc/annonc741
GIMR	2025-10-19	FL	2	ERBB2	Overexpression, Protein expression, Low protein expression	Urothelial carcinoma	Disitamab vedotin + Toripalimab	Phase 3. RC48-C016 trial. NCT05302284. N=484. Disitamab vedotin + toripalimab significantly improved PFS (13.1 vs 6.5 months), OS (31.5 vs 16.9 months), and ORR (76.1% vs 50.2%) over chemotherapy in patients with untreated HER2-expressing locally advanced or metastatic urothelial carcinoma.	41124210, ESMO25.LBA7
GIMR	2023-06-04	FL	2	ERBB2	Protein expression; Overexpression	Biliary tract cancer	Zanidatamab	Not TGA approved. FDA approved (accelerated). Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months. 	37276871
GIMR	2021-09-19	FL	2	ERBB2	S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA (Y772_A775dup), A775_G776insTVMA, G776S, G776delinsVC, V777L, P780_Y781insGSP (G778_P780dup), G778_S779insLPS, Exon 20 insertion, Exon 20 mutation	Non-small cell lung cancer	Trastuzumab deruxtecan	Not TGA approved. FDA approved. DESTINY-Lung01. Phase 1/2. N=91. ORR 50/91 (55%). Median DOR 9.3 months. Median PFS 8.2 months. Median OS 17.8 months. DCR 84/91 (92%).	34534430, 10.1016/annonc/annonc741
GIMR	2022-05-24	FL	2	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Elacestrant	Not TGA approved. FDA approved 27/01/2023. Phase 3. EMERALD trial. In patients with ER-postive HER2-negative metastatic breast cancer treated with prior CDK4/6 inhibitor and up to 2 lines of endocrine therapy, SERD Elacestrant significantly improved PFS over standard-of-care endocrine therapy (6 month PFS rate: 34% vs 20%, 12 month PFS: 22 vs 9%).	35584336
GIMR	2025-10-19	FL	2	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Giredestrant + Everolimus	Phase 3 evERA BC trial. NCT05306340. N=373. Giredestrant + everolimus significantly improved PFS over SOC ET + everolimus (8.8 vs 5.5 months) in ER+, HER2- advanced breast cancer patients previously treated with a CDK4/6 inhibitor.	ESMO25.LBA16
GIMR	2026-03-03	FL	2	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and ESR1:Oncogenic mutations, ESR1:D538G, ESR1:Y537S, ESR1:Y537N 	Breast cancer	Camizestrant + Palbociclib; Camizestrant + Ribociclib; Camizestrant + Abemaciclib	Not TGA approved. Phase 3 SERENA-6 trial, NCT04964934, N=315, ER-positive, HER2-negative advanced breast cancer, ESR1 mutation detected in ctDNA, patients switched to camizestrant (75mg daily) or continued aromatase inhibitor, both with CDK4/6 inhibitor, median PFS 16.0 months (camizestrant) vs 9.2 months (aromatase inhibitor). 	40454637
GIMR	2026-03-03	FL	2	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and ESR1:Oncogenic mutations	Breast cancer	Vepdegestrant	Phase 3 VERITAC-2 trial, NCT05654623, N=624, Vepdegestrant, a PROTAC ER degrader, significantly improved PFS over fulvestrant in ER-positive, HER2-negative advanced breast cancer patients with ESR1 mutations (5.0 vs 2.1 months, HR 0.58), but not in the overall population (3.8 vs 3.6 months, HR 0.83).	40454645
GIMR	2025-10-19	FL	2	ERBB2+ESR1+PIK3CA	PIK3CA:oncogenic mutations + ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Gedatolisib + Fulvestrant + Palbociclib; Gedatolisib + Fulvestrant;	Phase 3 VIKTORIA-1 trial. NCT055001886. N=392. Gedatolisib + fulvestrant with or without palbociclib significantly improved PFS (9.3 vs 2.0 months)in HR+/HER2-/PIK3CA WT advanced breast cancer patients. ORR was 32% (triplet), 28.3% (doublet), and 1% (fulvestrant).	ESMO25.LBA17
GIMR	2022-05-22	FL	2	ESR1	Oncogenic mutations	Breast cancer	Elacestrant	Not TGA approved. Phase 3. EMERALD trial. In patients with ER-postive HER2-negative metastatic breast cancer treated with prior CDK4/6 inhibitor and up to 2 lines of endocrine therapy also harbouring a ESR1 mutation, Elacestrant significantly improved PFS over standard-of-care endocrine therapy (6 month PFS rate: 41% vs 19%, 12 month PFS: 27 vs 8%). Stratification by ESR1 mutation is prespecified.	35584336
GIMR	2022-10-07	FL	2	ESR1	Oncogenic mutations	Breast cancer	Fulvestrant + Palbociclib	Phase 3. PADA-1. NCT03079011. Median PFS from randomisation was significantly longer in patients switching to Fulvestrant + Palbociclib from Aromatase Inhibitor + Palbociclib (11.9 vs 5.7 months) in patients after detection of rising ESR1 resistance mutation in the circulating tumour DNA assay.	36183733
GIMR	2025-06-01	FL	2	ESR1	Oncogenic mutations, D538G, Y537S, Y537N	Breast cancer	Camizestrant + Palbociclib; Camizestrant + Ribociclib; Camizestrant + Abemaciclib 	Phase 3 SERENA-6 trial. NCT04964934. In patients with ER-positive, HER2-negative advanced breast cancer with emerged ESR1 mutation, switching to camizestrant with continued CDK4/6 inhibitor resulted in significantly longer PFS (16.0 months vs 9.2 months) compared to continuing aromatase inhibitor plus CDK4/6 inhibitor.	10.1200/JCO.2025.43.17_suppl.LBA4
GIMR	2026-03-03	FL	2	ESR1+ERBB2	ESR1:Protein expression AND ERBB2:Amplification, ESR1:Protein expression AND ERBB2:Overexpression	Breast cancer	Trastuzumab + Pertuzumab + Palbociclib + Letrozole; Trastuzumab + Pertuzumab + Palbociclib + Anastrozole; Trastuzumab + Pertuzumab + Palbociclib + Fulvestrant	Phase 3. PATINA. NCT02947685. N=518. Addition of palbociclib to maintenance HER2-targeted and endocrine therapies significantly improved progression-free survival compared to standard therapy (median 44.3 vs 29.1 months)	41604639
GIMR	2025-07-30	FL	2	ESR1+ERBB2	ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Imlunestrant	Phase 3 EMBER-3 trial. NCT04975308. N=874. Imlunestrant (N=331) demonstrated significantly longer PFS than standard therapy in ESR1-mutant patients (5.5 vs 3.8 months; HR 0.70; 95% CI 0.54-0.91; P<0.001) but showed no difference in the overall population (HR 0.87; 95% CI 0.72-1.04; P=0.12). Imlunestrant-abemaciclib combination (N=213) significantly improved PFS over imlunestrant monotherapy (9.4 vs 5.5 months; HR 0.57; 95% CI 0.44-0.73; P<0.001). 	39660834
GIMR	2026-03-04	FL	2	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Abemaciclib + Fulvestrant	Phase 3. postMONARCH. NCT05169567. N=368. Abemaciclib plus fulvestrant improved investigator-assessed PFS over placebo plus fulvestrant (HR 0.73; median 6.0 vs 5.3 months) in HR+, HER2- advanced breast cancer after CDK4/6i progression. BICR PFS HR 0.55. ORR 17% versus 7%. Consistent effect across ESR1 and PIK3CA mutation subgroups.	39693591
GIMR	2026-03-04	FL	2	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Datopotamab deruxtecan	FDA approved. Phase 3. TROPION-Breast01. NCT05104866. N=732. HR+/HER2- metastatic breast cancer. Dato-DXd significantly improved PFS versus chemotherapy (HR, 0.63). OS trend favored Dato-DXd (HR, 0.84). Consistent PFS benefit across subgroups.	39265124
GIMR	2022-06-06	FL	2	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Sacituzumab govitecan	NCT03901339. Phase 3. Tropics-02: In hormone receptor-positive, HER2-negative metastatic breast cancer, Sacituzumab govitecan significantly improved median PFS (5.5 vs 4.0 months) over treatment of physician choice.	36027558, JCO.2022.40.17_suppl.LBA1001
GIMR	2025-10-19	FL	2	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Sacituzumab tirumotecan 	Phase 3 OptiTROP-Breast02 study. NCT06081959. N=399. Sacituzumab tirumotecan significantly improved PFS over investigator's choice of chemotherapy (8.3 vs 4.1 months) with a manageable safety profile in patients with previously treated HR+/HER2- breast cancer.	ESMO25.LBA23
GIMR	2025-07-30	FL	2	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Imlunestrant + Abemaciclib	Phase 3 EMBER-3 trial. NCT04975308. N=874. Imlunestrant (N=331) demonstrated significantly longer PFS than standard therapy in ESR1-mutant patients (5.5 vs 3.8 months; HR 0.70; 95% CI 0.54-0.91; P<0.001) but showed no difference in the overall population (HR 0.87; 95% CI 0.72-1.04; P=0.12). Imlunestrant-abemaciclib combination (N=213) significantly improved PFS over imlunestrant monotherapy (9.4 vs 5.5 months; HR 0.57; 95% CI 0.44-0.73; P<0.001). 	39660834
GIMR	2026-03-03	FL	2	ESR1+ERBB2	NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Triple-negative breast cancer	Sacituzumab govitecan	Phase 3 ASCENT-03 trial, NCT05382299, N=558, Sacituzumab govitecan significantly improved PFS (9.7 months vs 6.9 months) over chemotherapy in patients with untreated advanced triple-negative breast cancer not eligible for PD-1/PD-L1 inhibitors, with similar ORR (48% vs 46%) and higher median duration of response (12.2 vs 7.2 months).	41124233
GIMR	2024-10-13	FL	2	ESR1+ERBB2+PIK3CA	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression and PIK3CA:Oncogenic mutations	Breast cancer	Inavolisib + Palbociclib + Fulvestrant	Not TGA approved. FDA approved. Phase 3. INAVO120 trial. NCT04191499. N=325. Inavolisib + palbociclib + fulvestrant significantly improved PFS2 (24.0 vs 15.1 months) and Time to first chemotherapy (not estimable vs 15.0 months) over placebo in patients with PIK3CA-mutated, hormone receptor-positive, HER2-negative locally advanced/metastatic breast cancer. OS improved (34.0 months vs 27.0 months).	40454641, 10.1200/JCO.2024.42.16_suppl.1003
GIMR	2020-06-19	FL	2	EZH2	Oncogenic mutations	Follicular lymphoma	Tazemetostat	Not TGA registered. FDA approved. NCT01897571	10.1182/blood-2019-128096, 29650362
GIMR	2022-08-31	FL	2	FGFR1	Rearrangement, Fusion	Myelodysplastic/myeloproliferative diseases; Myeloproliferative diseases; Acute lymphoblastic leukaemia; Acute myeloid leukaemia	Pemigatinib	Not TGA approved. FDA approved. Phase 2. FIGHT-203. NCT03011372. CR was achieved in 14 of 18 patients with chronic phase (78%) and 2 in 4 patients with blast Phase 1n the marrow. 22 of 28 patients (79%) achieved complete cytogenetic response.	10.1182/blood-2021-148103
GIMR	2022-07-26	FL	2	FGFR2	Fusion, FGFR2-POC1B fusion, FGFR2 rearrangement	Cholangiocarcinoma	Futibatinib	Not TGA approved. FDA approved 30/09/2022. NCT02052778. TAS-120-101. Phase 1 dose expansion. Overall, the ORR of the study was 14% (25% in cholangiocarcinoma). In the 20 mg daily dose cohort (N=64), ORR was 16% and DCR was 72%. DOR 5.3 months. In the 16 mg cohort (N=16), ORR was 42% (8/19). Responders included patients previously treated with other FGFR inhibitors.	34551969
GIMR	2023-07-05	FL	2	FGFR2	Fusion, Oncogenic mutations	Urothelial carcinoma	Erdafitinib	Phase 3. THOR. Compared with chemotherapy, erdafitinib achieved a median PFS 5.6 months (v 2.7 months. HR 0.58) and OS (12.1 v 7.8 months, HR 0.64).ORR was 46 vs 12 %.	10.1200/JCO.2023.41.17_suppl.LBA4619
GIMR	2020-05-31	FL	2	FGFR2	Fusions	Cholangiocarcinoma	Futibatinib	Not TGA approved. FDA approved 30/09/2022. NCT02052778. FOENIX-CCA2. Single-arm Phase 2 study. Intrahepatic cholangiocarcinoma. ORR 42% (43/103). DCR was 83%. median PFS 9.0 months. Median OS 21.7 months.	36652354, 10.1200/JCO.2020.38.15_suppl.108, 10.1200/JCO.2022.40.16_suppl.4009
GIMR	2020-06-11	FL	2	FGFR2	Fusions	Cholangiocarcinoma	Infigratinib	Not TGA approved. FDA accelerated approved for use in second-line and beyond. Phase 2 study (NCT02150967) with N=108. ORR: 23%. Median PFS 7.3 months.	10.1200/JCO.2021.39.3_suppl.265, 10.1200/JCO.2020.38.15_suppl.4591
GIMR	2020-04-27	FL	2	FGFR2	Fusions, FGFR2-BICC1 fusion, FGFR2-CASP7 fusion	Urothelial carcinoma	Erdafitinib	Not TGA approved. FDA approved. Phase 2. BLC2001. NCT02365597. Erdafitinib showed an objective response rate of 40% (3% complete response, 37% partial response) in previously treated patients with locally advanced or metastatic urothelial carcinoma with FGFR alterations, with median PFS of 5.5 months and OS of 13.8 months.	31340094
GIMR	2020-04-27	FL	2	FGFR3	Fusions, FGFR3-TACC3 fusion, FGFR3-BAIAP2L1 fusion, R248C, S249C, G370C, Y373C	Urothelial carcinoma	Erdafitinib	Not TGA approved. FDA approved. Phase 2. BLC2001. NCT02365597. Erdafitinib showed an objective response rate of 40% (3% complete response, 37% partial response) in previously treated patients with locally advanced or metastatic urothelial carcinoma with FGFR alterations, with median PFS of 5.5 months and OS of 13.8 months.	31340094
GIMR	2023-07-05	FL	2	FGFR3	S249C, Y373C, R248C, G370C, Fusion, FGFR1-TACC3:fusion, FGFR1-TACC3:fusion_V1, FGFR1-TACC3:fusion_V3, FGFR3-BAIAP2L1 fusion	Urothelial carcinoma	Erdafitinib	Not TGA approved. FDA approved. Phase 3 trial. THOR. NCT03390504. In the subsequent line setting, Erdafitinib resulted in significantly longer overall survival than chemotherapy (12.1 months vs 7.8 months) among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. ORR were 39% (Erdafitinib), versus 10% (Chemotherapy).	37870920, 10.1200/JCO.2023.41.17_suppl.LBA4619
GIMR	2020-09-21	FL	2	FLT3	Internal tandem duplication	Acute myeloid leukaemia	Sorafenib	Not TGA approved for AML. In allogeneic SCT population. 1Y Relapse 7% vs 24.5%	32791048
GIMR	2022-11-16	FL	2	FOLR1	Protein expression	Ovarian cancer	Mirvetuximab soravtansine	Not TGA approved. FDA approved 14/11/2022. SORAYA. NCT04296890.	33667670
GIMR	2023-12-09	FL	2	FOLR1	Protein expression	Ovarian cancer	Mirvetuximab soravtansine	Phase 3 trial. MIRASOL. NCT04209855. N=453. In platinum-resistant ovarian cancer, Mirvetuximab soravtansine showed significant improvement in PFS (median, 5.6 months v chemotherapy, 3.9 months), ORR (42% vs 16%) and OS (16.5 vs 12.8 months) over chemotherapy. 	38055253
GIMR	2022-06-06	FL	2	Homologous Recombination Deficiency Score	High	Ovarian cancer	Rucaparib	Phase 3. NCT03522246. ATHENA-MONO. In advanced epithelial ovarian cancer, In HRD population, PFS was significantly prolonged in Rucaparib arm over placebo (28.7 v 11.3 months). Note PFS was also significantly prolonged in ITT population (20.2 v 9.2 months).	35658487
GIMR	2020-05-09	FL	2	Homologous Recombination Deficiency Score	High	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Olaparib + Bevacizumab	Biomarker and drug combination not TGA approved; FDA approved as maintenance therapy after first-line platinum-based chemotherapy. PAOLA-1 trial. Companion diagnostic for olaparib: MyChoice CDX with HRD score of 42 or higher indicated a positive test.	31851799
GIMR	2020-05-31	FL	2	Homologous Recombination Deficiency Score	High	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Veliparib	Not TGA approved. PFS 31.9 vs 20.5 months in the HRD cohort. HRD positivity is defined as HRD score >= 33 on myChoice CDx assay.	31562800
GIMR	2023-06-05	FL	2	IDH1	Oncogenic mutation	Low-grade gliomas	Vorasidenib	Phase 3. NCT04164901. INDIGO. N=331. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26).	37272516, 41175888
GIMR	2020-04-27	FL/XT	2	IDH1	R132	Acute myeloid leukaemia	Ivosidenib	Not TGA approved. FDA approved. 	29860938
GIMR	2021-07-02	FL	2	IDH1	R132	Acute myeloid leukaemia	Olutasidenib	Not TGA approved. FDA approved 2022-12-01. Phase 2. NCT02719574. Interim anaylsis. ORR 57% (46/123). CR 30% (37/123). Median OS 10.5 months with duration of treatment 5.5 months.	10.1200/JCO.2021.39.15_suppl.7006
GIMR	2022-05-30	FL	2	IDH1	R132C, R132H, R132G, R132L, R132S	Acute myeloid leukaemia	Ivosidenib + Azacitidine	FDA approved. Not TGA approved. Phase 3 AGILE. NCT03173248. In previously untreated IDH1 mutant AML, adding ivosidenib to azacitidine significantly prolonged both EFS and OS (median 24.0 vs 7.9 months).	35443108
GIMR	2023-06-05	FL	2	IDH2	Oncogenic mutation	Low-grade glioma	Vorasidenib	Phase 3. NCT04164901. INDIGO. N=331. Grade 2 with mutant IDH. Vorasidenib is associated with improvement with radiologic PFS 27.7 v 11.1 months and time to the next intervention (HR 0.26)	37272516
GIMR	2020-06-15	FL	2	JAK2	V617F	Myelofibrosis	Fedratinib	Not TGA approved. FDA approved. Phase 2, JAKARTA-2, NCT01523171, N=97, Fedratinib achieved a spleen response in 55% (46/83) of assessable patients with ruxolitinib-resistant or ruxolitinib-intolerant myelofibrosis, with common grade 3-4 adverse events including anaemia (38%) and thrombocytopenia (22%).	28602585
GIMR	2020-04-16	FL	2	KIT	D816V	Mastocytosis	Avapritinib	Not TGA approved. FDA approved 16/6/2021 based on EXPLORER (NCT02561988) and PATHFINDER (NCT03580655) data.	10.1182/blood-2018-99-112017
GIMR	2020-05-16	FL	2	KIT	Oncogenic mutations, V654A, T670I, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P	Gastrointestinal stromal tumour	Sorafenib	Not TGA approved. Not FDA approved. NCCN recommended 2A. Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842.	10.1200/jco.2011.29.15_suppl.10009, 22270258, 22665524
GIMR	2020-05-07	FL	2	KIT	Oncogenic mutations; Exon 11 mutation; Exon 9 mutation	Gastrointestinal stromal tumour	Imatinib; Sunitinib	Not TGA approved by NGS unless IHC positive	18955458
GIMR	2020-05-15	FL	2	KIT	Oncogenic mutations; Exon 11 mutation; Exon 9 mutation	Gastrointestinal stromal tumour	Regorafenib	Not TGA approved by NGS unless IHC positive	23177515
GIMR	2021-07-02	FL	2	KIT	Protein expression, Oncogenic mutations	Gastrointestinal stromal tumour	Pimitespib	Phase 3. CHAPTER-GIST-301. Single-agent Pimitespib in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure. Median PFS was 2.8 vs. 1.4 mo (placebo). Median OS: 13.8 vs 9.6 mo (placebo). Pimitespib was also effective in patients who had secondary KIT resistance.	10.1200/JCO.2021.39.15_suppl.11524
GIMR	2020-04-16	FL	2	KIT	T670I	Gastrointestinal stromal tumour	Regorafenib	Not TGA approved by NGS unless IHC positive	10.1200/jco.2013.31.15_suppl.10510
GIMR	2020-05-15	FL	2	KIT	V654A, T670I	Gastrointestinal stromal tumour	Sunitinib	Not TGA approved by NGS unless IHC positive	19164557
GIMR’	2025-07-30	FL	3	KMT2A	Rearrangement	Acute myeloid leukaemia	Ziftomenib	Phase 1/2 KOMET-001. NCT04067336. N=83. Ziftomenib showed 25% complete remission or remission with partial hematologic recovery in 36 KMT2A rearrangement/NPM1 mutation patients at 600 mg (recommended phase 2 dose), including 35% remission rate in 20 NPM1 mutation patients.	39401509
GIMR	2024-12-06	FL	2	KMT2A	Rearrangement	Acute myeloid leukaemia; Acute lymphoblastic leukaemia; Mixed phenotype acute leukaemia	Revumenib	FDA approved. Not TGA approved. Phase 1/2. AUGMENT-101 trial. NCT04065399. N=94. Revumenib led to high remission rates with 23% of complete remission rate and 63% ORR in relapsed/refractory KMT2Ar acute leukaemia.	39121437
GIMR	2026-03-04	FL	2	KRAS	G12C	Colorectal adenocarcinoma	Sotorasib + Panitumumab	FDA approved. Phase 3 CodeBreaK 300. NCT05198934. N=160. Sotorasib 960 mg-panitumumab significantly prolonged PFS versus investigator's choice in chemorefractory KRAS G12C mCRC. Updated ORR 30.2% (95% CI, 18.3 to 44.3) for 960 mg, 7.5% for 240 mg, and 1.9% for investigator's choice. OS HR 0.70 (95% CI, 0.41 to 1.18) for 960 mg and 0.83 (95% CI, 0.49 to 1.39) for 240 mg versus investigator's choice. Median follow-up 13.6 months. Findings support sotorasib 960 mg-panitumumab as standard of care.	40215429
GIMR	2023-05-05	FL	2	KRAS	G12C	Colorectal cancer	Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. N=29. Divarasib plus cetuximab had a manageable safety profile and encouraging antitumor activity in KRAS G12C-positive CRC. The confirmed ORR was 63% (18/29, KRAS G12C inhibitor-naive patients). The median duration of response was 6.9 months, and the median PFS was 8.1 months.	38052910
GIMR	2023-10-23	FL	2	KRAS	G12C	Colorectal cancer	Sotorasib + Panitumumab	Phase 3 trial. CodeBreaK 300. NCT05198934. N=160. Sotorasib + panitumumab showed longer progression-free survival (PFS) than standard treatment in chemorefractory metastatic colorectal cancer with mutated KRAS G12C. Median PFS: 5.6 months and 3.9 months for sotorasib at doses of 960 mg and 240 mg, respectively; 2.2 months for standard treatment (HR, 0.49 and 0.58, respectively). Overall survival data are maturing. Objective response rate: 26.4%, 5.7%, and 0% in the sotorasib-panitumumab groups and standard-care group, respectively. Treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2%, and 43.1% of patients, respectively.	37870968
GIMR	2021-06-05	FL	2	KRAS	G12C	Non-small cell lung cancer	Adagrasib	Not TGA approved. FDA approved 12/12/2022. NCT03785249. In patients with previously treated metastatic non-small cell lung cancer, treatment with adagrasib resulted in ORR of 48/112 (43%), median PFS of 6.5 months and median OS of 12.6 months.	35658005
GIMR	2025-06-01	FL	2	KRAS	G12C	Non-small cell lung cancer	Adagrasib + Pembrolizumab	Phase 2 KRYSTAL-7 study. NCT04613596. N=149. Adagrasib plus pembrolizumab showed an ORR of 44.3% and median OS of 18.3 months in patients with advanced/metastatic KRASG12C-mutated NSCLC, with varying efficacy across different PD-L1 expression levels.	10.1200/JCO.2025.43.16_suppl.8500
GIMR	2020-04-16	FL	2	KRAS	G12R, G13C, R149C	Histiocytosis	Cobimetinib	Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations	30867592
GIMR	2022-06-06	FL	2	KRAS	NOT oncogenic mutations	Pancreatic adenocarcinoma	Nimotuzumab + Gemcitabine	Phase 3. NOTABLE. In previously untreated KRAS-wild type pancreatic cancer, addition of nimotuzumab to gemcitabine significantly improved survival over gemcitabine alone (10.9 vs. 8.5 months), one-year OS rate of 44% v 27%, and 3 year OS rate of  14% vs 3%.	37647576; 10.1200/JCO.2022.40.17_suppl.LBA4011
GIMR	2025-05-26	FL	2	KRAS	Oncogenic mutation	Low-grade serous ovarian cancer	Avutometinib + Defactinib	FDA granted accelerated approval to avutometinib and defactinib for KRAS-mutated recurrent low-grade serous ovarian cancer based on RAMP-201 trial (NCT04625270, N=57) results showing an ORR of 44% and DOR range of 3.3-31.1 months. Publication pending.	10.1200/JCO.2023.41.16_suppl.5515, NCT04625270
GIMR	2020-04-27	FL	2	Loss-of-heterozygosity score	High	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Rucaparib	Not TGA approved. FDA approved. Companion test FoundationFocus CDxBRCA LOH (cut off 16%). ARIEL3 trial: Note a low LOH is also associated with thus the biomarker not differentiating treatment benefit.	28916367
GIMR	2020-04-16	FL	2	MAP2K1	P142L, P124Q, Q56P, P105_107del	Histiocytosis	Cobimetinib; Trametinib	Phase 1/2 proof-of-concept trial. N=18. Cobimetinib showed an ORR of 89% in patients with histiocytic neoplasms, with durable responses and 94% of patients remaining progression-free at one year, regardless of genotype and presence of various MAPK-pathway mutations.	30867592
GIMR	2020-04-16	FL	2	MAP2K2	Oncogenic mutations, Y134H	Histiocytosis	Cobimetinib	Phase 1/2 proof-of-concept trial. N=18. Cobimetinib showed an ORR of 89% in patients with histiocytic neoplasms, with durable responses and 94% of patients remaining progression-free at one year, regardless of genotype and presence of various MAPK-pathway mutations.	30867592
GIMR	2023-09-08	FL	2	MET	Amplification	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Savolitinib	Not TGA approved. Not FDA approved. Phase 2. NCT04923932. Savolitinib monotherapy showed ORR of 45% in MET-amplified gastric cancer or gastro-oesophageal junction adenocarcinoma especially in those with high MET gene copy number. DOR rate at 4-month was 86%.	10.1158/1538-7445.AM2023-CT152
GIMR	2020-05-06	FL	2	MET	Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	Capmatinib	Not TGA approved. FDA approved 10/8/2022. Phase 2. GEOMETRY mono-1. NCT02414139. N=373. ORR in METex14 NSCLC was 68% (60 treatment-naive) and 44% (100 previously treated). Median follow-up 46.4 and 66.9 months respectively.\	32877583, 39362249, 10.1200/JCO.2019.37.15_suppl.9004
GIMR	2025-05-26	FL	2	MET	Overexpression	Non-small cell lung cancer	Telisotuzumab Vedotin	Not TGA approved. FDA approved (accelerated). Phase 2 LUMINOSITY trial. NCT03539536. N=172. Telisotuzumab vedotin showed an ORR of 28.6% in patients with c-Met protein-overexpressing nonsquamous EGFR-wildtype NSCLC, with a median DoR of 8.3 months and median OS of 14.5 months. ORR in c-Met high subgroup (≥50% of tumor cells with 3+ by SP44) was 35% (n=78) vs 23% Intermediate (25-50% of tumor cells with 3+, n=83). 	38843488
GIMR	2020-04-27	FL	2	Microsatellite Instability	High	Colorectal adenocarcinoma	Ipilimumab + Nivolumab	Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. Phase 2. Checkmate 142. N=45. ORR 69%. DCR 84%. Median PFS and OS not reached after follow up of 24 months. PFS at 24 months: 74%. Responses seen regardless of RAF/RAS mutational status. 	29355075, 34637336
GIMR	2020-04-27	FL	2	Microsatellite Instability	High	Colorectal adenocarcinoma	Nivolumab	Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. ORR 31%, DCR 69% at 12 weeks.	28734759
GIMR	2024-06-09	FL	2	Microsatellite Instability	High	Colorectal adenocarcinoma	Nivolumab + Ipilimumab	Phase 3. CheckMate 8HW. NCT04008030. N=303. Nivolumab + ipilimumab showed superior PFS over chemotherapy (HR 0.21; median not reached vs 5.9 months) in MSI-H/dMMR metastatic colorectal cancer patients, including improvement in PFS after the subsequent therapy.	10.1200/JCO.2024.42.16_suppl.3503
GIMR	2022-02-02	FL	2	Microsatellite Instability	High	Gastric cancer; Gastroesophageal junction adenocarcinoma	Pembrolizumab	Not TGA approved. Post hoc analysis of MSI-H group in three Phase 3 RCTs. In single-agent pembrolizumab, the ORR were 57%, 47%, and 57% for KEYNOTE-059, 061, and 062 respectively. The corresponding estimated 12 months OS rate were 71%, 73%, and 79% respectively. Analysis by MSI status was prespecified. Note MSI-H is provisionally approved for solid tumour by the TGA.	33792646
GIMR	2020-04-27	FL	2	Mismatch repair	Deficient	Colorectal adenocarcinoma	Ipilimumab + Nivolumab	Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. Phase 2. Checkmate 142. N=45. ORR 69%. DCR 84%. Median PFS and OS not reached after follow up of 24 months. PFS at 24 months: 74%. Responses seen regardless of RAF/RAS mutational status.  	29355075, 34637336
GIMR	2020-04-27	FL	2	Mismatch repair	Deficient	Colorectal adenocarcinoma	Nivolumab	Not TGA approved for MSI-H/dMMR. FDA accelerated approval based on CheckMate-142. ORR 31%, DCR 69% at 12 weeks.	28734759
GIMR	2024-06-09	FL	2	Mismatch repair	Deficient	Colorectal adenocarcinoma	Nivolumab + Ipilimumab	Phase 3. CheckMate 8HW. NCT04008030. N=303. Nivolumab + ipilimumab showed superior PFS over chemotherapy (HR 0.21; median not reached vs 5.9 months) in MSI-H/dMMR metastatic colorectal cancer patients, including improvement in PFS after the subsequent therapy.	10.1200/JCO.2024.42.16_suppl.3503
GIMR	2025-07-30	FL	2	Mismatch repair	Deficient	Endometrial cancer	Atezolizumab + Carboplatin + Paclitaxel	Phase 3 AtTEnd trial. NCT03603184. N=551. Median PFS was not estimable (95% CI 12.4-NE) for atezolizumab vs 6.9 months (6.3-10.1) for placebo in dMMR endometrial cancer (HR 0.36, p=0.0005); overall PFS 10.1 vs 8.9 months (HR 0.74, p=0.022). Median OS 38.7 vs 30.2 months (HR 0.82, log-rank p=0.048), with trial continuing for OS final analysis.	39102832
GIMR	2022-03-22	FL	2	Mismatch repair	High	Endometrial cancer	Pembrolizumab	Not TGA approved. FDA approved. Phase 2. NCT02628067. KEYNOTE-158, pooled analysis from Cohort D and K. N=79. ORR 48%. Median PFS: 13.1 months. Median DOR: not reached. Median OS: Not reached.	34990208
GIMR	2020-08-26	FL	2	MYD88	Oncogenic mutations, L265P	Waldenstroms macroglobulinaemia	Ibrutinib	Phase 2 study. NCT01614821. N=63. Ibrutinib demonstrated high activity in pretreated Waldenstrom's macroglobulinemia patients with an overall response rate of 91% and major response rate of 73%. Patients with MYD88(L265P)CXCR4(WT) mutations achieved the highest response rates at 100% overall response and 91% major response.	25853747
GIMR	2025-05-26	FL	2	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis	Mirdametinib	FDA approved. Phase 2b ReNeu trial. NCT03962543. N=114 (58 adults, 56 children). Mirdametinib showed confirmed ORR of 41% in adults and 52% in children with NF1-associated plexiform neurofibromatosis. Median target PN volumetric best response of -41% and -42% respectively, and improvement in pain and health-related quality of life.	39514826
GIMR	2024-06-23	FL	2	NF2	Oncogenic mutations (germline)	Vestibular schwannoma; Non-vestibular schwannoma; Meningioma; Ependymoma; Type 2 neurofibromatosis	Brigatinib	Phase 2. INTUITT-NF2. NCT04374305. N=40. Radiographic response in 10% of target tumors and 23% of all tumors from Brigatinib monotherapy. Benefit meningiomas and nonvestibular schwannomas, and hearing improvement in 35% of eligible ears. 	38904277
GIMR’	2025-07-30	FL	3	NPM1	Oncogenic mutation	Acute myeloid leukaemia	Ziftomenib	Phase 1/2 KOMET-001. NCT04067336. N=83. Ziftomenib showed 25% complete remission or remission with partial hematologic recovery in 36 KMT2A rearrangement/NPM1 mutation patients at 600 mg (recommended phase 2 dose), including 35% remission rate in 20 NPM1 mutation patients.	39401509
GIMR	2022-06-15	FL	2	NRG1	CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion	Solid tumours	Zenocutuzumab	Not TGA approved. FDA approved (accelerated). Phase 2 trial. NCT02912949. Updated results from phase 1/2 eNRGy trial. N=204. Zenocutuzumab showed efficacy in patients with advanced NRG1 fusion-positive cancer, with an ORR of 30% and median duration of response of 11.1 months; median PFS was 6.8 months. Response in PDAC was 42% in PDAC and 29% in NSCLC.	39908431, 10.1200/JCO.2022.40.16_suppl.105
GIMR	2020-04-27	FL	2	PDGFRA	D842V, Exon 18 mutation	Gastrointestinal stromal tumour	Dasatinib	Not TGA approved. Phase 2 single-arm trial. N=50. Dasatinib showed 6-month PFS rate of 29% and objective response in 25% of patients with imatinib-resistant GISTs, with a higher 6-month PFS rate of 50% in a subset of patients with pSRC expression.	29710216
GIMR	2020-04-27	FL	2	PDGFRA	D842V, Exon 18 mutation	Gastrointestinal stromal tumour	Regorafenib	Not TGA approved; NCCN Category 1 but not selected based on PDGFRA mutation	NCCN:sarcoma
GIMR	2020-04-27	FL	2	PDGFRA	Exon 18 mutation, D842V, D842_H845del	Gastrointestinal stromal tumour	Avapritinib	Not TGA approved; FDA approved. Phase 1 NAVIGATOR trial. NCT02508532.  Avapritinib showed antitumor activity in patients with advanced PDGFRA D842V-mutant gastrointestinal stromal tumors, with an overall response rate of 88% (5 complete responses, 44 partial responses). In the first-line setting at 300 mg (RP2D), ORR was 93% (26/28) with a CBR of 100%.	32615108, 10.1200/JCO.2019.37.15_suppl.11022
GIMR	2021-07-02	FL	2	PDGFRA	Oncogenic mutations	Gastrointestinal stromal tumour	Pimitespib	Phase 3 CHAPTER-GIST-301 trial. N=86. Pimitespib significantly improved PFS (2.8 months vs 1.4 months) and cross-over-adjusted OS (13.8 vs 9.6 months) compared with placebo in patients with advanced GIST refractory to standard TKIs. Single-agent Pimitespib was effective in treat-refractory GIST patients after imatinib, sunitinib, and regorafenib failure, including those with secondary KIT resistance.	35688358, 10.1200/JCO.2021.39.15_suppl.11524
GIMR	2023-11-29	FL	2	PIK3CA	Oncogenic mutation	Breast cancer	Capivasertib + Fulvestrant	Not TGA approved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy.	37256976
GIMR	2020-06-23	FL	2	PIK3CA	Oncogenic mutations	Breast cancer	Taselisib + Fulvestrant	Not TGA approved. Not FDA approved. Positive Phase 3 SANDPIPER with regards to median PFS (7.4 months) over placebo (5.4 mo). However, taselisib has limited clinical utility given safety profile and low magnitude of clinical benefit.	33186740, 10.1200/JCO.2018.36.18_suppl.LBA1006
GIMR	2020-09-21	FL	2	PTEN	Loss of protein expression; Loss-of-function mutations	Prostate cancer	Ipatasertib + Abiraterone	Not TGA approved. IPATential150. Radiological PFS of predefined subgroup by PTEN loss by IHC (co-primary endpoint) was significantly higher (18.5 months) in the ipatasertib group (vs 16.5 months in the abiraterone only group). Radiological PFS also corresponds to percentage of PTEN loss in tumour cells and PTEN loss by NGS.	34246347, 10.1016/j.annonc.2020.08.2250
GIMR	2023-11-29	FL	2	PTEN	Loss-of-function mutations, deletion	Breast cancer	Capivasertib + Fulvestrant	Not TGA approved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy.	37256976
GIMR	2022-06-04	FL	2	RET	Fusion	Solid tumours	Selpercatinib	Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001. NCT03157128. ORR was 44% (18/41 efficacy-evaluable population) with median DOR was 24.5 months.	36108661, 10.1200/JCO.2022.40.16_suppl.3094
GIMR	2020-12-19	FL	2	RET	Fusions, CCDC6-RET fusion, KIF5B-RET fusion	Non-small cell lung cancer	Pralsetinib	Not TGA approved. FDA approved. Phase 1/2 ARROW trial (NCT03037385, N=233) demonstrated pralsetinib efficacy with ORR 61% (53/87) and DCR 91% (79/87) in RET fusion-positive NSCLC patients previously treated with platinum-based chemotherapy, and 70% ORR in 27 treatment-naive patients.	34118197, 10.1200/JCO.2019.37.15_suppl.9008; 10.1200/JCO.2020.38.15_suppl.9515
GIMR	2020-05-08	FL	2	RET	Fusions, CCDC6-RET fusion, NCOA4-RET fusion, CCDC186-RET fusion, ERC1-RET fusion, KTN1-RET fusion, RUFY3-RET fusion	Thyroid cancer	Selpercatinib	Not TGA approved. FDA Approved. Phase 1/2 LIBRETTO-001 trial. NCT03157128. Selpercatinib showed durable efficacy with ORR of 69%, 73%, and 79% in RET-altered thyroid cancer patients, including those with prior vandetanib/cabozantinib treatment, treatment-naive, and RET fusion-positive thyroid cancer, respectively.	32846061, 10.1200/JCO.2018.36.15_suppl.102, 10.1200/JCO.2019.37.15_suppl.10045
GIMR	2020-05-08	FL	2	RET	Oncogenic mutations and NOT Amplification, M918T, V804L, V804M, Cysteine rich domain mutation	Medullary thyroid cancer; Thyroid cancer	Pralsetinib	Not TGA approved. FDA approved. Phase 2 ARROW. ORR 60% (33/55) in previously-treated MTC, 71% (15/21) treatment-naive MTC, and 89% (8/9) other RET-altered thyroid cancers.	34118198, 10.1200/JCO.2019.37.15_suppl.6018
GIMR	2020-05-08	FL	2	RET	Oncogenic mutations and NOT Amplification, M918T, V804M, V804L, C609, C611, C618, C620, C630, C634, D631_L633delinsE, E632_L633del, A883F, D631_L633delinsV, L790F, D898_E901del, D903_S904delinsEP, K666N, T636_V637insCRT, D378_G385delinsE	Medullary thyroid cancer	Selpercatinib	Not TGA approved. FDA Approved. LIBRETTO-001. ORR 69%	32846060, 10.1200/JCO.2020.38.15_suppl.3594
GIMR	2023-10-29	FL	2	RET	Oncogenic mutations, M918T	Medullary thyroid cancer	Selpercatinib	Not TGA approved. FDA approved. Phase 3 trial. LIBRETTO-531. NCT04211337. N=291. Selpercatinib had significantly longer PFS (HR, 0.28) and Treatment failure-free survival (HR, 0.25) compared to control group (cabozantinib or vandetanib) as first-line therapy in RET-mutant medullary thyroid cancer. ORR was 70% (cabozantinib/vandetanib: 39%). Adverse events led to dose reduction in 38.9% of the patients in selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively.	37870969
GIMR	2023-11-17	FL	2	ROS1	Fusion	Non-small cell lung cancer	Repotrectinib	Not TGA approved. FDA approved. Phase 2 NCT03093116. TRIDENT-1 trial. N=296. Repotrectinib showed durable clinical activity in ROS1 TKI-naïve (ORR=88%) and -pretreated pts with or without BL CNS mets, including intracranial responses.	38197815, 10.1200/JCO.2023.41.16_suppl.9017
GIMR	2020-04-25	FL	2	ROS1	Fusions	Non-small cell lung cancer	Lorlatinib	Not TGA approved; Not FDA approved; NCCN 2A recommendation as subsequent-line therapy. NCT03052608: ORR 50% (6 / 12). NCT01970865: Phase 1/2- ORR 62% (TKI-naive) and 35% (prior treatment with crizotinib) with good intracranial activities.	29074098, 31669155
GIMR	2024-06-02	FL	2	ROS1	Fusions, CD74-ROS1 fusion, SDC4-ROS1 fusion, EZR-ROS1 fusion, SLC34A2-ROS1 fusion, TPM3-ROS1 fusion, CD83-ROS1 fusion, LRIG1-ROS1 fusion, MYH9-ROS1 fusion, SDC4-ROS1 fusion, KLHDC2-ROS1 fusion. SLC34A2-ROS1 fusion, TPR-ROS1 fusion, G2101A, G2032R, L2026M, S1986F	Non-small cell lung cancer	Taletrectinib	Phase 2. TRUST-I study. NCT04395677. N=173. Taletrectinib showed high ORR (91% in TKI-naive, 52% in crizotinib-pretreated). PFS was NR (TKI-naive) and 7.6 months (crizotinib-pretreated.)	10.1200/JCO.2024.42.16_suppl.8520
GIMR	2026-03-04	FL	2	ROS1	Fusions; G2032R mutation	Non-small cell lung cancer	Taletrectinib	Phase 2. TRUST-I and TRUST-II. NCT04919811 and NCT04395677. N=273. ROS1+ NSCLC. Taletrectinib in TKI-naive patients (n=160): cORR 88.8%, IC-cORR 76.5%, median DOR 44.2 months, median PFS 45.6 months. In TKI-pretreated patients (n=113): cORR 55.8%, IC-cORR 65.6%, median DOR 16.6 months, median PFS 9.7 months. G2032R mutation cORR 61.5% (8 of 13).	40179330
GIMR	2020-11-10	FL	2	SMARCB1	Loss of protein expression, deletion	Epithelioid sarcoma	Tazemetostat	Not TGA approved. Phase 2 but FDA approved. NCT02601950	33035459, 10.1200/JCO.2019.37.15_suppl.11003
GIMR	2020-05-04	FL	2	SSTR2	Protein expression	Pancreatic neuroendocrine tumour; Neuroendocrine tumour	177Lu-DOTA-radioconjugate	Not TGA approved; FDA approved; Phase 3 NETTER-1 trial. NCT01578239. N=229. (177)Lu-Dotatate significantly improved PFS (65.2% vs 10.8% at 20 months) and ORR (18% vs 3%) compared to high-dose octreotide LAR in patients with advanced midgut neuroendocrine tumors.	28076709
GIMR	2025-07-30	FL	2	TNFRSF17	Protein expression	Multiple myeloma	Belantamab mafodotin + Bortezomib + Dexamethasone	Phase 3. DREAMM-7. NCT04246047. N=494. Belantamab mafodotin, bortezomib, dexamethasone (BVd) significantly improved PFS (36.6 vs 13.4 months, HR 0.41) over daratumumab, bortezomib, dexamethasone (DVd) in relapsed/refractory multiple myelo ma, with 84% vs 73% OS at 18 months, 25% vs 10% MRD-negative responses. Note that BCMA is a constitutively expressed target in myeloma and is not required for therapy selection.	38828933
GIMR	2025-07-30	FL	2	TNFRSF17	Protein expression	Multiple myeloma	Belantamab mafodotin + Pomalidomide + Dexamethasone	Phase 3 DREAMM-8. NCT04484623. N=302. BPd (belantamab mafodotin, pomalidomide, dexamethasone) improved progression-free survival (PFS) over PVd (71% vs 51% at 12 months, hazard ratio 0.52), with higher response rates (77% vs 72%) and deeper responses (40% vs 16% complete response). Note that BCMA is a constitutively expressed target in myeloma and is not required for therapy selection.	38828951
GIMR	2021-11-04	FL	2	TSC2	Loss-of-function mutations, Oncogenic mutations	Perivascular epithelioid cell tumour	Nab-sirolimus	FDA approved. Phase 2 AMPECT. ORR was 89% (8/9) in TSC2 mutant group. ORR was 2/16 (13%) in the non-TSC2 mutant group.	34637337
GIMR	2020-05-21	FL	3	ABL1	BCR-ABL1 Fusion	Acute lymphoblastic leukaemia	Bosutinib	Not TGA approved for ALL	10.1200/jco.2007.25.18_suppl.7006
GIMR	2020-05-21	FL	3	ABL1	BCR-ABL1 Fusion, T315I, E255K, E255V, Y253H, F359V, Q252H, G250H, E459K	Chronic myelogenous leukaemia	Asciminib		28329763, 31826340
GIMR	2020-05-21	FL	3	ABL1	E255K, E255V, F359C, F359I, F359V, Y253H, A337V, P465S	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Dasatinib	Requires presence of the BCR-ABL fusion transcript by PCR in either peripheral blood or bone marrow., and not TGA approved by biomarker.	20525995, 16775234
GIMR	2020-05-21	FL	3	ABL1	E255K, E255V,F317C, F317I, F317L, F317V, F359C, F359I, F359V, T315A, Y253H, A337V, P465S	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Bosutinib	Phase 3 BFORE trial. NCT02130557. Bosutinib demonstrated significantly higher MMR rate at 12 months (47.2% vs 36.9%) and CCyR rate by 12 months (77.2% vs 66.4%) compared to imatinib in patients with newly diagnosed chronic-phase CML. 	22949154, 24944159, 29091516
GIMR	2020-05-21	FL	3	ABL1	F317C, F317I, F317L, F317V, T315A, V299L, A337V, P465S	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Nilotinib	Phase 3 trial. NCT00471497. N=846. Nilotinib (300mg or 400mg twice daily) showed higher major molecular response rates (44% and 43% vs 22%) and complete cytogenetic response rates (80% and 78% vs 65%) compared to imatinib (400mg once daily) in patients with newly diagnosed chronic-phase Philadelphia chromosome-positive CML.	20525993, 16775235
GIMR	2022-07-27	FL	3	ABL1	NUP214-ABL1 fusion	T-cell acute lymphoblastic leukaemia	Imatinib	Case series. Nine of 11 complete responders seen in T-cell ALLs with extrachromosomal NUP214-ABL1 fusion treated with imatinib.	15361874
GIMR	2020-05-21	FL	3	ABL1	V299L, A337V, P465S	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Imatinib	Randomised study. N=1106. Imatinib showed superior major cytogenetic response (87.1% vs 34.7%), complete cytogenetic response (76.2% vs 14.5%), and freedom from progression to accelerated-phase or blast-crisis CML (96.7% vs 91.5%) compared to interferon alfa plus low-dose cytarabine in newly diagnosed chronic-phase CML. BCR-ABL1 fusion required, and not TGA approved by biomarker. 	12637609, 11287973
GIMR	2020-05-21	FL	3	ABL1	Y253H, E255K, E255V, V299L, F317L, F317C, F317I, F317V, F359C, F359V, F359I, A337V, P465S	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Ponatinib	BCR-ABL1 fusion required, and not TGA approved by biomarker. Adapted from APAR.	24180494
GIMR	2022-06-15	FL	3	AKT1	E17K	Breast cancer	Capivasertib + Fulvestrant	Phase 2. FAKTION. Biomarker analysis. In expanded pathway altered group (PIK3CA hotspot, AKT1 E17K, and PTEN altered), PFS was significantly prolonged when capiversertib was added to fulvestrant (12.8 months vs placebo, 4.6 months).  OS: 38.9 vs 20.0 months.	35671774, 10.1200/JCO.2022.40.16_suppl.1005
GIMR	2025-06-22	FL	3	AKT1	E17K	Breast cancer; Endometrial cancer	Ipatasertib	Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers.	10.1200/JCO.2024.42.16_suppl.3092
GIMR	2021-01-14	FL	3	AKT1	E17K	Solid tumours	Capivasertib	Phase 2 study. NCI-MATCH Subprotocol EAY131-Y. Confirmed ORR 28% with 1 CR. 6-month PFS: 50%. Subtypes that has demonstrated response: luminal breast cancers, uterine leiomyosarcoma, parotid gland carcinoma, and adenocarcinoma of cervix.	33377972
GIMR	2022-11-14	FL	3	AKT1	E17K	Solid tumours	Ipatasertib	NCT02465060. NCI-MATCH ECOG-ACRIN Trial (EAY131) Sub-protocol Z1K. ORR 22%. DOR 9.9 months.	10.1016/S0959-8049(22)00824-3
GIMR	2020-12-11	FL	3	AKT1	E17K	Triple-negative breast cancer	Capivasertib + Paclitaxel	Randomised phase 2 PAKT trial. N=140. Capivasertib + paclitaxel showed longer PFS (5.9 vs 4.2 months, NS) and OS (19.1 vs 12.6 months, NS) over placebo + paclitaxel in metastatic triple-negative breast cancer, with more pronounced magnitude (but non-significant) in patients with PIK3CA/AKT1/PTEN-altered tumors (PFS: 9.3 vs 3.7 months).	31841354
GIMR	2020-05-15	FL	3	AKT1	E17K	Triple-negative breast cancer	Ipatasertib + Paclitaxel	Phase 2 LOTUS trial. NCT02162719. N=124. Ipatasertib + paclitaxel improved PFS over placebo + paclitaxel (6.2 vs 4.9 months) in metastatic triple-negative breast cancer, with more pronounced effect in PTEN-low population (6.2 vs 3.7 months, NS).	28800861
GIMR	2020-05-27	FL	3	ALK	C1156Y, C1156T, L1196M	Non-small cell lung cancer	Ensartinib	Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors.	28122866
GIMR	2020-05-27	FL	3	ALK	C1156Y, C1156T, L1196M	Non-small cell lung cancer	Entrectinib	Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors.	28122866
GIMR	2020-04-16	FL	3	ALK	EML4-ALK Fusion, Fusions	Non-small cell lung cancer	Ensartinib	Phase 2 trial. NCT03215693. Ensartinib showed an ORR of 52% in crizotinib-resistant, ALK-positive NSCLC patients, with 70% intracranial ORR in patients with measurable brain metastases, and was generally well-tolerated with mostly grade 1 or 2 treatment-related adverse events.	31628085
GIMR	2020-04-16	FL	3	ALK	EML4-ALK Fusion, Fusions, VCL-ALK fusion, CAD-ALK fusion, F1245V	Non-small cell lung cancer	Entrectinib	Phase 1/2 ALKA-372-001 and STARTRK-1 trials. Entrectinib demonstrated antitumor activity in TKI-naive patients with ALK fusions, achieving an ORR of 57% (4/7) with a median duration of response of 7.4 months. 	28183697, 10.1200/jco.2015.33.15_suppl.2517
GIMR	2020-04-16	FL	3	ALK	F1245V	Non-small cell lung cancer	Entrectinib	Phase 1/2 ALKA-372-001 and STARTRK-1 trials. ALK F1245V mutant neuroblastoma achieved durable confirmed partial response lasting 8.3 months.	28183697, 10.1200/jco.2015.33.15_suppl.2517
GIMR	2024-07-03	FL	3	ALK	Fusion	Non-small cell lung cancer	APG-2449	Phase 1/2. APG-2449. NCT03917043. N=144. ORR was 68% in ROS1 TKI-naive and 796% in ALK TKI-naive patients. In 2G ALK inhibitor-resistant patients, ORR was 41%, mPFS was 11.9 months. Encouraging intracranial ORR was seen.	10.1200/JCO.2024.42.16_suppl.3124
GIMR	2026-03-04	FL	3	ALK	Fusion	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2022-10-18	FL	3	ALK	Fusion	Solid tumours	Crizotinib	Phase 2 NCI-MATCH (EAY131) Subprotocol F. NCT02465060. Crizotinib showed a response rate of 50% (1 complete response) in 4 eligible patients with ALK rearrangements and 25% in patients with ROS1 rearrangements, with median PFS of 3.8 and 4.3 months, and median OS of 4.3 and 6.2 months, respectively.	35233056
GIMR	2021-03-04	FL	3	ALK	G1202R, G1202del, F1174, L1196M, G1269A, I1171	Non-small cell lung cancer	Lorlatinib	Loratinib has activities in patients who developed acquired resistance to first and second generation TKIs. ORR 42-89% across the list of mutations.	30892989
GIMR	2020-05-27	FL	3	ALK	I1151ins, L1152P, L1152R, C1156Y, C1156T, F1174C, F1174L, F1174V, L1196M, S1206C, S1206Y, G1269A, G1269S	Non-small cell lung cancer	Brigatinib	Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors.	28122866
GIMR	2020-05-27	FL	3	ALK	I1151ins, L1152P, L1152R, C1156Y, C1156T, I1171T, I1171N, I1171S, F1174C, F1174L, F1174V, L1196M, G1202R, S1206C, S1206Y, E1210K, G1269A, G1269S	Non-small cell lung cancer	Lorlatinib	Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors.	28122866
GIMR	2020-05-27	FL	3	ALK	I1171T, I1171N, L1196M, S1206C, S1206Y, G1269A, G1269S	Non-small cell lung cancer	Ceritinib	Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors.	28122866
GIMR	2020-05-27	FL	3	ALK	L1152P, L1152R, C1156Y, C1156T, F1174C, F1174L, F1174V, L1196M, S1206C, S1206Y, G1269A, G1269S	Non-small cell lung cancer	Alectinib	Review article discusses the mechanisms of resistance to ALK tyrosine kinase inhibitors.	28122866
GIMR	2021-03-04	FL	3	ALK	R1275Q	Neuroblastoma	Crizotinib	Phase 2 study. ADVL0912. While crizotinib showed limited activity with an ORR of 15% in patients with relapsed/refractory ALK-positive neuroblastoma, with responses seen in patients with ALK Arg1275Gln mutation."	33568345
JGKB	2020-04-16	FL	3	APC	Loss-of-function mutations; oncogenic mutations	Aggressive fibromatosis	Nirogacestat	Phase 2. N=17. PF-03084014, a gamma-secretase inhibitor, showed clinical activity in patients with desmoid tumors, with confirmed partial responses in evaluable patients who remained on study for over 2 years. A total of 15 patients had APC or CTNNB1 mutations. ORR was 29% (5/17), and 5/17 had stable disease. Neither APC loss-of-function nor CTNNB1 gain-of-function mutations was selected prospectively, but these are known central alterations in aggressive fibromatosis. Responses were observed regardless of mutation status.	28350521
GIMR	2025-06-16	FL	3	APC	Loss-of-function mutations; oncogenic mutations	Aggressive fibromatosis	Varegacestat	Phase 2 RINGSIDE trial. NCT04871282. Varegacestat showed an Objective Response Rate (ORR) of 64% and Disease Control Rate (DCR) of 97% in patients with desmoid tumors, with a median best change in tumor volume of -85% and a well-tolerated safety profile at the recommended 1.2 mg QD dose. Responses were seen in both PC (43%, n=7) and CTNNB1 (68%, n=19) mutations.	10.1016/j.annonc.2024.08.1857, 10.1200/JCO.2025.43.16_suppl.11516
GIMR	2024-07-17	FL	3	AR	Ligand-binding domain mutation	Prostate cancer	ARV-766	Phase 1/2 study. NCT05067140. N=103. In castration-resistant prostate cancer patients with AR LBD mutations resulted in PSA50 of 50%.	10.1200/JCO.2024.42.16_suppl.5011
GIMR	2021-10-12	FL	3	AR	Overexpression	Salivary gland cancers	Abiraterone Acetate + Leuprorelin; Abiraterone Acetate + Triptorelin; Abiraterone Acetate + Goserelin	Phase 2. NCT02867852. N=24. Median PFS: 3.7 months. Median OS: 22.5 months. ORR 21%. DCR 63%. AR overexpression is defined as combined score expression = 6.	34597119
GIMR	2021-06-07	FL	3	AR	Protein expression	Breast cancer	Proxalutamide	Phase 1B: NCT04103853. AR positivity defined as >1% IHC.	10.1200/JCO.2021.39.15_suppl.1019
GIMR	2023-11-28	FL	3	AR	Protein expression	Salivary gland cancers	Apalutamide + Goserelin	Phase 2. NCT04325828. AR-expressing SGC, pts treated with APA and GOS. ORR (6/24) was 25%. Clinical benefit rate and DCR were 50% and 70.8%, respectively. PFS and OS in the treated pts were 7.4 months and not reached, respectively.	10.1200/JCO.2022.40.16_suppl.6079
GIMR	2020-04-25	ST	3	AR	Protein expression	Salivary gland cancers	Bicalutamide	Phase 2 trial. AR-positive salivary gland carcinoma. CAB (leuprorelin acetate + bicalutamide) showed an ORR of 41.7% and CBR of 75.0%, with median PFS of 8.8 months and median OS of 30.5 months.	29211833
GIMR	2020-04-25	FL	3	AR	Protein expression	Triple-negative breast cancer	Enzalutamide	Phase 2 trial. NCT01889238. Enzalutamide demonstrated clinical activity with a CBR at 16 weeks of 25% in the ITT population and 33% in the evaluable subgroup, and was well tolerated in patients with advanced AR-positive TNBC.	29373071, 10.1200/jco.2015.33.15_suppl.1003
GIMR	2021-06-07	FL	3	AR+ESR1	AR:Protein expression and ESR1:Protein expression	Breast cancer	Enobosarm	Phase 2 trial. NCT02463032. N=136. Enobosarm in postmenopausal women with AR-positive, ER-positive, HER2-negative advanced breast cancer demonstrated clinical benefit rates of 32% (9mg cohort) and 29% (18mg cohort) at 24 weeks. AR positivity was defined by IHC positive cell percentage, with nuclei staining percentage correlating with ORR and CBR.	38342115, 10.1200/JCO.2021.39.15_suppl.1020
GIMR	2021-11-05	FL	3	ARID1A	Oncogenic mutations AND Loss of protein expression	Solid tumours	Ceralasertib	Phase 2. Interim result from NCT03682289. N=10 in the ARID1A-deficient cohort (defined as negative IHC staining for BAF250a). ORR 20% (2/10) with both responders being CR. One patient with prolonged SD (8.8 month). Accrual is ongoing.	10.1016/j.annonc.2021.08.1034
GIMR	2023-10-02	FL	3	ATM	Oncogenic mutation	Solid tumours	Olaparib + Durvalumab	Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 38% and ORR was 3 /32 (9%) non-BRCA-mutated groups. Only responders were seen in patients with ATM mutations. 	37365284
GIMR	2023-10-02	FL	3	BAP1	Loss of protein expression	Mesothelioma	Rucaparib	Phase 2 MiST. NCT03654833. Ten and 23 of 26 patients were BRCA1 and BAP1 protein expression negative, respectively. DCR at 12 week was 58%, and 23% at 24 weeks, meeting prespecified criteria.	33515503
GIMR	2024-08-29	FL	3	BAP1	Loss of protein expression, Oncogenic mutations	Mesothelioma	Tazemetostat	Phase 2. NCT02860286. N=74. Tazemetostat showed DCR of 54% at week 12 in patients with BAP1-inactivated pleural mesothelioma, meeting the primary endpoint of the study. Two PR were seen.	35588752
GIMR	2022-09-07	FL	3	BRAF	G469R, A598_T599insV, AGAP3-BRAF fusion, L597Q, T470R	Melanoma	Trametinib	Phase 2. NCT02296112. Trametinib in non-V600 BRAF mutation and BRAF fusions. ORR was 33% (3/9). Median PFS 7.3 months.	33861486
GIMR	2020-04-16	FL	3	BRAF	KIAA1549-BRAF fusion, V600E	Low-grade gliomas; Paediatric low grade gliomas	Selumetinib	Phase 2. NCT01089101. N=50. Selumetinib achieved sustained partial response in 36% (9/25) of patients with BRAF-aberrant pilocytic astrocytoma and 40% (10/25) of patients with NF1-associated paediatric low-grade glioma.	31151904
GIMR	2022-03-26	FL	3	BRAF	V600	Anaplastic ganglioglioma; Anaplastic thyroid cancer; Cholangiocarcinoma; Biliary tract cancer; Erdheim-Chester disease; High-grade glioma; Langerhans cell histiocytosis; Low-grade glioma; Non-small cell lung cancer; Neuroendocrine carcinoma; Ovarian cancer; Salivary gland cancers; Sarcoma; Solid tumours except Colorectal adenocarcinoma, pancreatic adenocarcinoma	Vemurafenib	VE-BASKET. Phase 2. ORR of 33% (170) with median DOR 13 months. The selected cancer type has at least one responders. 	32029534
GIMR	2020-12-30	FL	3	BRAF	V600	Colorectal adenocarcinoma	Vemurafenib + Cobimetinib	Phase 2 TAPUR trial. NCT not specified. N=30. Cobimetinib plus vemurafenib showed antitumor activity in CRC patients with BRAF mutations, with disease control rate of 52% and ORR of 30%, rejecting the null hypothesis of 15% disease control rate (P < .0001). Median duration of therapy was 8.1 weeks. Median PFS was 15.7 weeks.	36409971, 10.1200/JCO.2020.38.4_suppl.122
GIMR	2023-12-22	FL	3	BRAF	V600	Hairy cell leukaemia; Erdheim-Chester disease	Vemurafenib	Phase 2. AcSé vemurafenib basket study. NCT01895643. N=98. Vemurafenib showed clinical activity in BRAF mutated cancers including HCL (ORR 89.7%), ECD (80%), ovarian cancer (50%) and cholangiocarcinoma (18%). Median PFS was 8.8 months. Response were also seen in glioblastoma, ovarian, xanthoastrocytoma, ganglioglioma, sarcoma, GI adenocarcinoma, and prostate cancer.	37922690
GIMR	2023-12-22	FL	3	BRAF	V600	Solid tumour	Vemurafenib	Phase 2. AcSé vemurafenib basket study. NCT01895643. N=98. Vemurafenib showed clinical activity in BRAF mutated cancers including HCL (ORR 89.7%), ECD (80%), ovarian cancer (50%) and cholangiocarcinoma (18%). Median PFS was 8.8 months. Response were also seen in glioblastoma, ovarian, xanthoastrocytoma, ganglioglioma, sarcoma, GI adenocarcinoma, and prostate cancer.	37922690
GIMR	2023-11-20	FL	3	BRAF	V600, fusions	Solid tumour	FORE8394	Phase 1/2a FORE8394-201 study. NCT02428712. N=110. ORR in the treatment naive cohort was 39% (9/23); 18% (3/17) in previously treated with MAPKi.	10.1200/JCO.2023.41.16_suppl.3006
GIMR	2020-12-31	FL	3	BRAF	V600E	Colorectal adenocarcinoma	Cetuximab + Irinotecan + Vemurafenib	Phase 2 SWOG S1406. Triplet including vemurafenib (vs without) improved ORR (17 v 4%) with improved PFS (4.2 v 2.0 mo).	33356422
GIMR	2022-07-18	FL	3	BRAF	V600E	Colorectal adenocarcinoma	Dabrafenib + Trametinib	Phase 2. NCT01072175. ORR 12% in pretreated CRC with PFS of 3.5 months.	26392102
GIMR	2020-04-16	FL	3	BRAF	V600E	Colorectal adenocarcinoma	Panitumumab + Dabrafenib + Trametinib	Phase 1/2 trial evaluating combined BRAF, EGFR, and MEK inhibition in 142 patients with BRAF(V600E)-mutant colorectal cancer, showing confirmed response rates of 10% for dabrafenib + panitumumab, 21% for dabrafenib + trametinib + panitumumab, and 0% for trametinib + panitumumab.	29431699
GIMR	2023-10-03	FL	3	BRAF	V600E	Hairy cell leukaemia	Vemurafenib + Obinutuzumab	Phase 2. NCT03410875. N=30. Vemurafenib plus obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL. Acquired vemurafenib resistance or dose-limiting toxicity was not observed in this small study.	10.1056/EVIDoa2300074
GIMR	2020-04-16	FL	3	BRAF	V600E	Low-grade gliomas	Dabrafenib + Trametinib	Phase 1/2 study. NCT02124772. N=139. Trametinib monotherapy and combination with dabrafenib showed clinical efficacy in pediatric BRAF V600-mutant low-grade glioma with ORR of 15% and 25% respectively, and manageable safety.	36375115, 10.1200/JCO.2020.38.15_suppl.10506
GIMR	2021-06-04	FL	3	BRAF	V600E	Papillary craniopharyngioma	Vemurafenib + Cobimetinib	Phase 2 Alliance A071601. NCT03224767. N=16. BRAF-MEK inhibitor combination vemurafenib-cobimetinib showed 94% objective response rate (15 of 16 patients) with 91% median reduction in tumor volume in patients with BRAF-mutated papillary craniopharyngiomas.	37437144, 10.1200/JCO.2021.39.15_suppl.2000
GIMR	2020-04-16	FL	3	BRAF	V600E	Papillary thyroid cancer	Dabrafenib	Phase 1/2 study. Dabrafenib stimulated radioiodine uptake in 60% (6/10) of patients with BRAF V600E-mutant iodine-refractory papillary thyroid cancer, with 2 partial responses and 4 stable disease after subsequent iodine-131 treatment.	25285888, 25549723
GIMR	2020-04-16	FL	3	BRAF	V600E	Papillary thyroid cancer	Vemurafenib	Phase 2 trial. NCT01286753. Vemurafenib showed antitumour activity with a best overall response of 38.5% in patients with BRAF(V600E)-positive papillary thyroid cancer refractory to radioactive iodine who had never been treated with a multikinase inhibitor.	23489023, 27460442
GIMR	2021-06-12	FL	3	BRAF	V600E	Solid tumours	Vemurafenib + Cobimetinib	Phase 2. TAPUR. NCT02693535. Across many tumour types, ORR was 57%, DCR was 68%, and DOR was 20.5 weeks. PFS 5.8 months.	10.1200/JCO.2022.40.16_suppl.3008
GIMR	2025-05-27	FL	3	BRAF	V600E	Solid tumours; Non-small cell lung cancer	Vemurafenib + Cobimetinib	Phase 2 trial. MoST substudy 12. ACTRN12620000861954. N=64. VEM+COB achieved ORR of 50% in refractory BRAF V600-mutated solid tumours and 42% in 1L NSCLC, with median PFS of 7.9 months and OS of 15.9 months in solid tumour group, and 6-mo PFS rates of 68% and 67% in solid and 1L NSCLC groups respectively.	10.1016/j.annonc.2024.08.690
GIMR	2021-08-10	FL	3	BRAF	V600E, V600K	Colorectal adenocarcinoma	Encorafenib + Binimetinib	Phase 2. NCT01543698. N=11. Encorafenib plus binimetinib showed confirmed responses in 18% (2/11) of mCRC. DCR at 6 months: 7/11 (64%).	32669376
GIMR	2021-11-10	FL	3	BRAF	V600E, V600K, V600M	Non-small cell lung cancer	Vemurafenib	Phase 2. AcSé. NCT02304809. ORR: 43 of 96 (45%) patients. Median PFS 5.2 months. Median OS 10 months.	31959346
GIMR	2023-10-02	FL	3	BRCA1	Loss of protein expression	Mesothelioma	Rucaparib	Phase 2 MiST. NCT03654833. 10 and 23 of 26 patients were BRCA1 and BAP1 protein expression negative, respectively. DCR at 12 week was 58%, and 23% at 24 weeks, meeting prespecified criteria.	33515503
GIMR	2026-02-02	FL	3	BRCA1	Oncogenic mutations	Hepatocellular carcinoma	Talazoparib	Phase 2 TAPUR Study. N=28. Talazoparib demonstrated antitumor activity in patients with BRCA1/2-mutated solid tumors, with a DCR of 57% and ORR of 36%, including responses in tumor types not currently approved for PARP inhibitors.	38865672
GIMR	2026-03-06	FL	3	BRCA1	Oncogenic mutations	Ovarian cancer	Avelumab + Talazoparib	Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 63.6% in platinum-sensitive, BRCA1/2-altered OC (n=20, median PFS not reached, DOR not reached). Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials.	36394849
GIMR	2025-06-11	FL	3	BRCA1	Oncogenic mutations	Ovarian cancer	Olaparib	Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer.	21862407
GIMR	2026-02-02	FL	3	BRCA1	Oncogenic mutations	Solid Tumours	Olaparib	Phase 2. Belgian Precision trial. BRCA1/2-mutated advanced cancers. N=27 (BRCA1) and 27 (BRCA2). ORR 11% (27 BRCA1: 3 PRs including pancreatic, gallbladder) and 21% (27 BRCA2: 5 PRs in pancreatic, parathyroid, and 1 CR in colon). Median PFS ≥14 months (5-34+ months in responders). CBR 63% (BRCA1) and 46% (BRCA2).	37852034
GIMR	2020-09-21	FL	3	BRCA1	Oncogenic mutations (germline)	Breast cancer	Durvalumab + Olaparib	Phase 1/2 MEDIOLA trial. NCT02734004. N=34. Olaparib + durvalumab demonstrated antitumour activity in breast cancer patients (TNBC and non-TNBC) with maximum two prior treatment lines. In germline BRCA-mutated metastatic breast cancer, ORR was 63% with 80% disease control rate at 12 weeks and 50% at 28 weeks. PD-L1 status (1% threshold) was not significant. 	32771088
GIMR	2021-06-07	FL	3	BRCA1	Oncogenic mutations (germline)	Breast cancer	Pamiparib	Phase 2: NCT03575065. ORR 38% in TNBC and 62% in HR-positive germline BRCA mutated population. Median PFS 5.5 months (TNBC) and 9.2 months (HR-positive) respectively.	10.1200/JCO.2021.39.15_suppl.1087
GIMR	2020-04-25	FL	3	BRCA1	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Cisplatin + Gemcitabine	Phase 2 trial. N=50. Cisplatin and gemcitabine with or without veliparib in germline BRCA1/2 or PALB2 positive PDAC. ORR was 74% (arm A), 65% (arm B) (P = .55). DCR was 100% (arm A) vs 78.3% (arm B) (P = .02). Median PFS 10.1 months (arm A) vs 9.7 months (arm B) (P = .73). Median OS 15.5 months (arm A) vs 16.4 months (arm B) (P = .6).	31976786
GIMR	2021-05-12	FL	3	BRCA1	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Rucaparib	Phase 2 trial of maintenance Rucaparib (after first-line chemotherapy) in platinum-sensitive advanced pancreatic cancer. PFS6 60% with median 13.1 months. ORR 42% in 36 patients. 	33970687
GIMR	2020-06-11	FL	3	BRCA1	Oncogenic mutations (germline)	Triple-negative breast cancer	Cisplatin + Veliparib	Randomised phase 2. SWOG S1416S1416 trial. NCT02595905. N=320. Cisplatin + veliparib significantly improved PFS in BRCA-like metastatic triple-negative breast cancer patients (5.9 months vs 4.2 months) but not in germline BRCA1/2-mutated or non-BRCA-like groups.	36623515, 10.1200/JCO.2020.38.15_suppl.1001
GIMR	2022-02-28	FL	3	BRCA1	Oncogenic mutations (germline), Oncogenic mutations	Prostate cancer	Niraparib	Phase 2. GALAHAD. NCT02854436. Objective response in the BRCA cohort (N=142) was 34%. 	35131040
GIMR	2020-05-30	FL	3	BRCA1	Oncogenic mutations AND NOT Oncogenic mutations (germline)	Breast cancer	Olaparib	Phase 2 TBCRC 048 study. Olaparib showed an ORR of 33% in cohort 1 and 31% in cohort 2, with confirmed responses seen in somatic BRCA1/2 (50%) mutation carriers, and median PFS of 6.3 months.	33119476, 10.1200/JCO.2020.38.15_suppl.1002
GIMR	2024-06-02	FL	3	BRCA1	Oncogenic mutations AND NOT Oncogenic mutations (germline)	Breast cancer	Olaparib	Phase 2 TBCRC-048. N=54. Olaparib showed ORR of 75% in gPALB2-mutated MBC (Cohort 1a) and 36.7% in sBRCA-mutated MBC (Cohort 2a), with median PFS of 9.6 months and 5.6 months, respectively	10.1200/JCO.2024.42.16_suppl.1021
GIMR	2021-06-28	FL	3	BRCA1	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer	Ceralasertib + Olaparib	Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 50% (6/12).	37097611, 10.1200/JCO.2021.39.15_suppl.5516
GIMR	2022-06-19	FL	3	BRCA1+BRCA2	NOT BRCA1:Oncogenic mutations (germline) and NOT BRCA2:Oncogenic mutations (germline)	Triple-negative breast cancer	ZEN-3694 + Talazoparib	In germline BRCA-wildtype TNBCs, BET inhibitor ZEN-3694 creates “BRCAness” and renders sensitive to Talazoparib. Activity was demonstrated in the phase 2 portion of the trial met primary endpoint with CBR 30% (11/37). ORR was 22% (11/50) in the combined phase 1b and 2 cohort.	10.1200/JCO.2022.40.16_suppl.1023
GIMR	2026-03-06	FL	3	BRCA2	Oncogenic mutations	Ovarian cancer	Avelumab + Talazoparib	Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 63.6% in platinum-sensitive, BRCA1/2-altered OC (n=20, median PFS not reached, DOR not reached). Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials.	36394849
GIMR	2025-06-11	FL	3	BRCA2	Oncogenic mutations	Ovarian cancer	Olaparib	Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer.	21862407
GIMR	2020-05-31	FL	3	BRCA2	Oncogenic mutations	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Veliparib	Not TGA approved; Negative subgroup	31562800
GIMR	2020-06-02	FL	3	BRCA2	Oncogenic mutations	Pancreatic adenocarcinoma	Rucaparib	RUCAPANC. 16 gBRCA1/2; 3 tBRCA with 2 PR + 1CR (1 unconfirmed CR).Conflicting efficacy signal.	30051098
GIMR	2021-09-09	FL	3	BRCA2	Oncogenic mutations	Prostate cancer	Talazoparib	TALAPRO-1. Phase 2. ORR 46% (26/57).	34388386
GIMR	2026-02-02	FL	3	BRCA2	Oncogenic mutations	Prostate cancer; Cutaneous squamous cell carcinoma; Pancreatic adenocarcinoma; Gastric cancer; Oesophageal adenocarcinoma; Mesothelioma; Non-small cell lung cancer; Ovarian cancer; Endometrial cancer	Talazoparib	Phase 2 TAPUR Study. N=28. Talazoparib demonstrated antitumor activity in patients with BRCA1/2-mutated solid tumors, with a DCR of 57% and ORR of 36%, including responses in tumor types not currently approved for PARP inhibitors.	38865672
GIMR	2026-02-02	FL	3	BRCA2	Oncogenic mutations	Solid Tumours	Olaparib	Phase 2. Belgian Precision trial. BRCA1/2-mutated advanced cancers. N=27 (BRCA1) and 27 (BRCA2). ORR 11% (27 BRCA1: 3 PRs including pancreatic, gallbladder) and 21% (27 BRCA2: 5 PRs in pancreatic, parathyroid, and 1 CR in colon). Median PFS ≥14 months (5-34+ months in responders). CBR 63% (BRCA1) and 46% (BRCA2).	37852034
GIMR	2023-10-02	FL	3	BRCA2	Oncogenic mutations	Solid tumours	Olaparib + Durvalumab	Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 35% and ORR was 3 /16 (19%) BRCA-mutated groups. All responders harboured BRCA2 mutations.	37365284
GIMR	2020-09-21	FL	3	BRCA2	Oncogenic mutations (germline)	Breast cancer	Olaparib + Durvalumab	MEDIOLA breast cancer cohort, including both TNBC and non-TNBC. Maximum of two lines of prior treatments. ORR 63%. DCR 28 weeks: 50%. Note: PD-L1 (at 1%) status NS.	32771088
GIMR	2021-06-07	FL	3	BRCA2	Oncogenic mutations (germline)	Breast cancer	Pamiparib	Phase 2: NCT03575065. ORR 38% in TNBC and 62% in HR-positive germline BRCA mutated population. Median PFS 5.5 months (TNBC) and 9.2 months (HR-positive) respectively.	10.1200/JCO.2021.39.15_suppl.1087
GIMR	2020-04-25	FL	3	BRCA2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Cisplatin + Gemcitabine	Phase 2 trial. N=50. Cisplatin and gemcitabine with or without veliparib in germline BRCA1/2 or PALB2 positive PDAC. ORR was 74% (arm A), 65% (arm B) (P = .55). DCR was 100% (arm A) vs 78.3% (arm B) (P = .02). Median PFS 10.1 months (arm A) vs 9.7 months (arm B) (P = .73). Median OS 15.5 months (arm A) vs 16.4 months (arm B) (P = .6).	31976786
GIMR	2020-06-11	FL	3	BRCA2	Oncogenic mutations (germline)	Triple-negative breast cancer	Cisplatin + Veliparib	Randomised phase 2. SWOG S1416S1416 trial. NCT02595905. N=320. Cisplatin + veliparib significantly improved PFS in BRCA-like metastatic triple-negative breast cancer patients (5.9 months vs 4.2 months) but not in germline BRCA1/2-mutated or non-BRCA-like groups.	36623515, 10.1200/JCO.2020.38.15_suppl.1001
GIMR	2021-05-12	FL	3	BRCA2	Oncogenic mutations (germline), Oncogenic mutations	Pancreatic adenocarcinoma	Rucaparib	Phase 2 trial of maintenance Rucaparib (after first-line chemotherapy) in platinum-sensitive advanced pancreatic cancer. PFS6 60% with median 13.1 months. ORR 42% in 36 patients. 	33970687
GIMR	2022-02-28	FL	3	BRCA2	Oncogenic mutations (germline), Oncogenic mutations	Prostate cancer	Niraparib	Phase 2. GALAHAD. NCT02854436. Objective response in the BRCA cohort (N=142) was 34%. 	35131040
GIMR	2020-05-30	FL	3	BRCA2	Oncogenic mutations AND NOT Oncogenic mutations (germline)	Breast cancer	Olaparib	Phase 2 TBCRC 048 study. Olaparib showed an ORR of 33% in cohort 1 and 31% in cohort 2, with confirmed responses seen in somatic BRCA1/2 (50%) mutation carriers, and median PFS of 6.3 months.	33119476, 10.1200/JCO.2020.38.15_suppl.1002
GIMR	2024-06-02	FL	3	BRCA2	Oncogenic mutations AND NOT Oncogenic mutations (germline)	Breast cancer	Olaparib	Phase 2 TBCRC-048. N=54. Olaparib showed ORR of 75% in gPALB2-mutated MBC (Cohort 1a) and 36.7% in sBRCA-mutated MBC (Cohort 2a), with median PFS of 9.6 months and 5.6 months, respectively	10.1200/JCO.2024.42.16_suppl.1021
GIMR	2025-05-30	FL	3	BRCA2	Oncogenic mutations, Deletions	Uterine leiomyosarcoma	Olaparib; Talazoparib; Niraparib; Rucaparib	Retrospective analysis of 35 patients with BRCA-altered uterine sarcoma. N=13 treated with PARPis in recurrent/metastatic setting. ORR was 46% (1 CR, 5 PR). CBR was 62%. Median PFS was 13.2 months. Median PFS ratio compared to previous systemic therapy was 1.9. 60% ORR observed in patients with BRCA2 homozygous deletions.	40117531
GIMR	2021-06-28	FL	3	BRCA2	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer	Ceralasertib + Olaparib	Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).	10.1200/JCO.2021.39.15_suppl.5516
GIMR	2025-05-04	FL	3	CBL	Y371H, C384R	Juvenile myelomonocytic leukaemia	Trametinib	Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months.	38867349
GIMR	2022-12-08	FL	3	CCNE1	Amplification	Ovarian cancer; Solid tumours	Adavosertib	Phase 2. NCT03253679. NCI 10136. Adavosertib monotherapy. N=33. ORR 27%. Median PFS 4.1 months. Median OS as 9.9 months. In epithelial ovarian cancer, ORR was 36% and DCR at 6 months of 57%. CCNE1 amplification was determined by NGS platforms at the threshold of genomic copy number of > 7 copies.	36469840
GIMR	2026-03-04	FL	3	CD123	Overexpression	Blastic plasmacytoid dendritic cell neoplasm	Pivekimab sunirine	Phase 1/2. NCT03386513. Pivekimab sunirine (PVEK) showed a composite complete response rate of 75% in frontline de novo BPDCN patients, with median duration of response 10.6 months and median OS 16.6 months, and 53% proceeded to stem-cell transplant; in relapsed/refractory disease, CCR rate was 14%, with median duration 9.2 months and median OS 5.8 months.	41671533
GIMR	2020-06-18	FL	3	CD19	Overexpression	Diffuse large B-cell lymphoma	Tafasitamab + Lenalidomide	Phase 2 L-MIND study. NCT02399085. N=81. Tafasitamab plus lenalidomide showed antitumour activity with 60% ORR (43% CR, 18% PR) in patients with relapsed/refractory DLBCL ineligible for autologous stem-cell transplantation.	32511983
GIMR	2025-02-16	FL	3	CD20	Protein expression	Follicular lymphoma	Odronextamab	Phase 2 ELM-2 trial. NCT03888105. N=128. Odronextamab achieved an ORR of 80% and CR rate of 73.4%, with a median DoR of 25.1 months, PFS of 20.7 months, and OS not reached in patients with relapsed or refractory follicular lymphoma. Note of level of CD20 expression was not associated with responses irrespective at baseline, CRs seen in no or low proportions of CD20-positive cells.	39147364
GIMR	2022-02-27	FL	3	CD274	Protein expression	Cervical cancer	Balstilimab + Zalifrelimab	Phase 2. NCT03495882. ORR in PD-L1 positive subgroup 33% (22/67). ORR in PD-L1 negative subgroup was 9% (3/33). Overall DCR was 52%. The PD-L1 assay was measured by combined positive score >= 1% using 22C3 PharmDx assay.	34932394
GIMR	2026-03-04	FL	3	CD274	Protein expression	Cervical cancer	Camrelizumab + Famitinib; Camrelizumab	Phase 2 randomized trial. NCT04680988. N=194. Camrelizumab plus famitinib versus camrelizumab in pretreated recurrent or metastatic cervical cancer. ORR per BICR significantly improved (41.0% vs 24.1%; P=.0181). Median PFS 8.1 vs 4.1 months. Median OS 20.2 vs 14.9 months. ORR benefit consistent across PD-L1 positive (44.6% vs 23.5%) and PD-L1 negative (35.0% vs 25.0%) subgroups, numerically higher in PD-L1 subgroup. Median DoR 16.0 months.	40561369
GIMR	2020-04-16	FL	3	CD274	Protein expression	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Pembrolizumab	Not TGA approved. KEYNOTE-059: Phase 2 single arm study in previously treated disease (third-line and beyond). ORR: 16% in PD-L1 positive group (defined as CPS >= 1%, 22C3 pharmDx assay). DOR: 16.3 months. FDA accelerated approval in 2017, but reviewed 2021 due to low response rate and negative confirmatory trial KEYNOTE-061.	29543932
GIMR	2022-05-17	FL	3	CD274	Protein expression	Non-small cell lung cancer	Atezolizumab + Tiragolumab	Randomized phase 2 study. CITYSCAPE. NCT03563716. In chemotherapy naive, PD-L1-positive population, mMedian PFS was 5.4 months in tiragolumab plus atezolizumab versus 3.6 months in the atezolizumab group. ORR was 31% (tiragolumab + atezolizumab) v 16% (atezolizumab). PD-L1 positivity was defined as Tumour Proportion Score >= 1% using Dako 22C3 IHC pharma Dx assay.	10.1016/S1470-2045(22)00226-1
GIMR	2025-04-23	FL	3	CD274	Protein expression	Non-small cell lung cancer	Cadonilimab + Anlotinib	Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and activity with an ORR of 51% (25/49) at 15mg/kg Q3W and 60% (12/20) at 10mg/kg Q3W as first-line treatment in advanced NSCLC. ORRs differed between PD-L1-positive (60.5%) and PD-L1-negative (42.3%) patients. PD-L1 expression was assessed by immunohistochemistry using PD-L1 IHC 22C3 pharmDx (Dako Omnis), with PD-L1 positivity defined as a tumor proportion score (TPS) ≥1%. High PD-L1 expression was not required for entry into the trial.	38110665
GIMR	2020-06-29	FL	3	CD274	Protein expression	Oesophageal squamous cell carcinoma	Camrelizumab	Subgroup analysis showed that PD-L1 positive subgroup (defined as TPS >= 1%) derives more benefits	32416073
GIMR	2021-03-19	FL	3	CD274	Protein expression	Triple-negative breast cancer	Pembrolizumab	KEYNOTE-119 previously treated TNBC: Single-agent pembrolizumab versus investigator-choice chemotherapy. Failed to meet prespecified primary point of OS (12.7 v 11.6mo) and pre-specified PD-L1 endpoint (as assessed by combined positive score of 1% or greater). However, in the exploratory anaylsis, CPS of 20 or more was associated with higher ORR (26% vs 12%) and OS (14.9 vs 12.5 months).	33676601
GIMR	2020-06-29	FL	3	CD274	Protein expression	Urothelial carcinoma	Durvalumab	TGA conditionally approved but not PBS reimbursed. ORR difference was found between PD-L1 high vs low groups. PD-L1 positivity is defined as >= 25% of either tumour or immune cells staining for PD-L1 using Ventana SP-263 assay. NB: TGA approval was based on response rate. NCT01693562. Note FDA Approval withdrawn in Feb 2021, based on Phase 3 DANUBE trial results.	28817753
GIMR	2026-03-03	FL	3	CD276	Protein expression	Small-cell lung cancer	Ifinatamab Deruxtecan	Phase 2 IDeate-Lung01 trial, NCT05280470, N=183, Ifinatamab Deruxtecan 12 mg/kg showed ORR of 48.2%, median DOR of 5.3 months, median PFS of 4.9 months, and 9-month OS estimate of 59.1%. Note no meaningful association was observed between B7-H3 expression by IHC and treatment response (Figure S1). 	41086386
GIMR	2024-09-14	FL	3	CD276	Protein expression	Solid tumours; Small-cell lung cancer; Nasopharyngeal carcinoma; Non-small cell lung cancer; Pulmonary lymphoepithelioma-like carcinoma	YL201	Phase 1/1b trial. NCT05434234 and NCT06057922. N=312. YL201, a B7H3-targeting antibody-drug conjugate, demonstrated antitumor activity in heavily pretreated patients with objective response rates of 63.9% in ES-SCLC, 48.6% in NPC, and 54.2% in LELC, prompting ongoing phase 3 trials for SCLC and NPC. All tumors expressed B7H3, but no significant correlation was seen between B7H3 expression levels and response across different tumour types. Updated 2025-06-29	40082695, 10.1016/j.annonc.2024.08.672
GIMR	2020-05-04	FL	3	CDK4	Amplification	Dedifferentiated liposarcoma	Palbociclib	Phase 2 trial. NCT01209598. N=60. Palbociclib achieved a 12-week PFS of 66% in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma, exceeding the primary endpoint, with median PFS of 18 weeks.	23569312, 27124835
GIMR	2020-05-04	FL	3	CDK4	Amplification	Well-differentiated liposarcoma	Palbociclib	Phase 2 trial. NCT01209598. N=60. Palbociclib achieved a 12-week PFS of 66% in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma, exceeding the primary endpoint, with median PFS of 18 weeks.	23569312, 27124835
GIMR	2022-02-21	FL	3	CDKN2A	Loss of protein expression	Mesothelioma	Abemaciclib	Phase 2. MiST2. NCT03654833. In p16ink4A-deficient, treatment with single-agent abemaciclib resulted in CBR of 14/26 (54%), with an ORR of 12% (3/26). Median PFS: 128 days. Median OS: 217 days.	35157829
GIMR	2024-06-02	FL	3	CDKN2A	Oncogenic mutation	Meningioma	Abemaciclib	Phase 2 Alliance A071401 trial. N=36. Abemaciclib improved PFS at 6 months of 54% in patients with recurrent or progressive grade 2/3 meningiomas and NF2 mutations or CDK pathway alterations, meeting primary endpoint. No objective responses observed.	10.1200/JCO.2024.42.16_suppl.2001
GIMR	2026-03-03	FL	3	CLDN18	Protein expression	Gastric cancer; Gastroesophageal junction adenocarcinoma	CMG901	Phase 1 KYM901 trial. NCT04805307. CMG901, a Claudin 18.2-targeting antibody-drug conjugate, antitumour activity in patients with advanced gastric or gastro-oesophageal junction cancer with confirmed ORR of 28% (32/113). CLDN18.2 positivity was defined as membrane staining intensity of >= 2+ in >= 5% of tumour cells in the the dose expansion phase.	39788133
GIMR	2024-09-15	FL	3	CLDN18	Protein expression	Gastric cancer; Gastroesophageal junction adenocarcinoma	SHR-A1904	Phase 1. NCT04877717. SHR-A1904 showed anti-tumor activity in 73 patients with GC/GEJC, with ORR of 56% at 6.0 mg/kg (DCR 89%). Claudin 18.2 positivity in ≥ 1% of cells	10.1016/j.annonc.2024.08.676
GIMR	2023-01-20	FL	3	CLDN18	Protein expression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Zolbetuximab + FOLFOX	Phase 2. ILUSTRO. N=19. In Claudin 18.2-positive, previously untreated locally advanced or metastatic GEJ cancers (Cohort 2), ORR was 63% (12/19), and median PFS was 13.7 months. 	10.1200/JCO.2021.39.15_suppl.e16063
GIMR	2024-11-04	FL	3	CLDN18	Protein expression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Zolbetuximab + FOLFOX	Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.	37490286
GIMR	2021-12-29	FL	3	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Emactuzumab	Phase 1. NCT01494688. Diffuse-type TGCT. N=28. ORR 84% (24/28) with two CR (7%) in combined dose escalation and expansion cohorts. Significant reduction in CD68/CD163-positive and CSF1R-positive macrophages was seen In 11 evaluable paired biopsy. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1.	26179200
GIMR	2021-12-29	FL	3	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Nilotinib	N=56. 93% Patients who were progression-free at 12 weeks. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1.	29571946
GIMR	2021-12-29	FL	3	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Pexidartinib	Phase 1. NCT01004861. N=23. Pexidartinib blocks the activity of CSF1R-dependent tumor-associated macrophage, required for tumour development. ORR was 52% (12/23) with partial response and DCR 83%. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1.	26222558
GIMR	2024-06-02	FL	3	CTAG1B	Protein expression, Overexpression	Synovial sarcoma; Myxoid liposarcoma; Round cell liposarcoma	Letetresgene autoleucel	Phase 2. IGNYTE-ESO substudy 2. NCT03967223. N=45. ORR was 40% (18/45) in patients with NY-ESO-1-expressing synovial sarcoma or myxoid/round cell liposarcoma. Median duration of response of 10.6 months.	10.1200/JCO.2024.42.16_suppl.2500
JGKB	2020-04-16	FL	3	CTNNB1	T41A, S45F, Gain-of-function mutations	Aggressive fibromatosis	Nirogacestat	N=17. A total of 15 patients had APC or CTNNB1 mutations. ORR was 29% (5/17), and 5/17 had stable disease. Neither APC loss-of-function or CTNNB1 gain-of-function mutations was selected prospectively, but are known central alteration in aggressive fibromatosis. Responses were seen regardless of APC or CTNNB1 mutations.	28350521
GIMR	2025-06-16	FL	3	CTNNB1	T41A, S45F, Gain-of-function mutations, Oncogenic mutations	Aggressive fibromatosis	Varegacestat	Phase 2 RINGSIDE trial. NCT04871282. Varegacestat showed an Objective Response Rate (ORR) of 64% and Disease Control Rate (DCR) of 97% in patients with desmoid tumors, with a median best change in tumor volume of -85% and a well-tolerated safety profile at the recommended 1.2 mg QD dose. Responses were seen in both APC (43%, n=7) and CTNNB1 (68%, n=19) mutations.	10.1016/j.annonc.2024.08.1857, 10.1200/JCO.2025.43.16_suppl.11516
GIMR	2025-05-31	FL	3	DLL3	High expression	Extrapulmonary neuroendocrine carcinoma	Obrixtamig	Phase 1 trial. NCT04429087. Obrixtamig showed greater efficacy in patients with extrapulmonary neuroendocrine carcinomas with high DLL3 expression (ORR: 40.0%, median DoR: 7.9 months) compared to those with low DLL3 expression (ORR: 3.3%). DLL3-high is defined as >50% TC.	10.1200/JCO.2025.43.16_suppl.3004
GIMR	2024-07-17	FL	3	DLL3	Protein expression	Prostate small cell carcinoma	Tarlatamab	Phase 1b study. NCT04702737. N=38 (evaluable patients with de novo or treatment-emergent neuroendocrine prostate cancer). ORR was 22% (4/38) and median PFS was 3.8 months in the DLL3+ subgroup. No response was seen in 20 evaluable patients. DLL3 positivity was defined by IHC in >= 1% of patients.	10.1200/JCO.2024.42.16_suppl.5012
GIMR	2023-10-29	FL	3	DLL3	Protein expression	Small-cell lung cancer	Tarlatamab	Phase 2. DeLLphi-301. NCT05060016. N=220. In patients with previously treated extensive stage SCLC. Tarlatamab showed antitumor activity, with ORR of 32-40% across seen in different dose groups and durable objective responses (>6 months) in 40 of 68 (59%) patients. Note DLL3 expression was not required as per trial eligibility but ubiquitously expressed  in SCLC. Objective responses were seen in patients with both positive, negative DLL3 expression.	37861218
GIMR	2026-03-04	FL	3	DLL3	Protein expression	Small-cell lung cancer; Extrapulmonary neuroendocrine carcinoma; Large cell neuroendocrine carcinoma of the lung	Obrixtamig	Phase I dose-escalation. NCT04429087. Obrixtamig (BI 764532). N=168. DLL3-positive SCLC, epNECs, or LCNEC-L. 72% received ≥2 lines prior therapy. Overall ORR 23% (95% CI, 17.4% to 30.2%). Median DoR 8.5 months (95% CI, 6.2 to not reached). 6-month DoR rate 70%. Regimens B2/B3 ORR 28%. Subgroup ORRs for SCLC 21%, epNECs 27%, and LCNEC-L 70%. Supports further exploration in heavily pretreated DLL3-positive tumors.	40706016
GIMR	2024-08-21	FL	3	DLL3	Protein expression	Small-cell lung cancer; Neuroendocrine carcinoma	BI 764532	Phase 1. NCT04429087. First-in-human dose-escalation trial of BI 764532 in DLL3-positive SCLC and NEC. N=90. At the target dose, ORR was 33% in SCLC and 22% in NEC.	10.1200/JCO.2023.41.16_suppl.8502
GIMR	2020-04-16	FL	3	EGFR	A763_Y764insFQEA	Non-small cell lung cancer	Afatinib; Gefitinib; Erlotinib	Not explicitly TGA listed. Comprehensive molecular profiling can identify uncommon EGFR mutations such as kinase domain duplications and rearrangements that are responsive to EGFR inhibitors in lung adenocarcinomas.	27413714, 10.1200/JCO.2019.37.15_suppl.e20593
GIMR	2020-06-28	FL	3	EGFR	C797S, Exon 20 insertion	Non-small cell lung cancer	Amivantamab	Phase 1. JNJ-61186372 demonstrated a manageable safety profile with preliminary responses in advanced NSCLC patients with EGFR-driven third-generation TKI-relapsed and Exon20ins disease, achieving 28% ORR (25/88) at ≥ 700 mg dose.	10.1200/JCO.2019.37.15_suppl.9009, 10.1200/JCO.2020.38.15_suppl.9512 
GIMR	2020-09-25	FL	3	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Amivantamab + Lazertinib	ORR 36% 15PR 1CR in osimertinib resistance cohort. ORR 100% treatment naive	10.1016/j.annonc.2020.08.1572
GIMR	2021-06-10	FL	3	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 1 CHRYSALIS. Combination treatment after osimertinib relapse. Dose expansion N=45. ORR 36%	10.1200/JCO.2021.39.15_suppl.9006
GIMR	2025-05-31	FL	3	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	DB-1310	Phase 1/2a trial. DB-1310, a HER3-targeted ADC, showed antitumor activity in heavily pretreated EGFRm NSCLC, with unconfirmed ORR of 44% (20/46) and median PFS of 7.0 months.	10.1200/JCO.2025.43.16_suppl.3000
GIMR	2026-03-03	FL	3	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 1/1b. CHRYSALIS-2 trial. NCT04077463. N=105. Amivantamab plus lazertinib demonstrated antitumor activity in patients with atypical EGFR-mutated advanced NSCLC, with an ORR of 52%, mDoR of 14.1 months , and mPFS of 11.1 months. In treatment-naive patients, ORR was 57%, mPFS was 19.5 months, and mDoR was 20.7 months. In previously treated patients, ORR was 48%, mPFS was 7.8 months, and mDoR was 11.0 months.	41325571
GIMR	2025-06-01	FL	3	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Patritumab deruxtecan	Phase 3 HERTHENA-Lung02 trial. NCT05338970. N=586. Patritumab deruxtecan showed significant improvement in PFS (HR, 0.77) over platinum-based chemotherapy in EGFR-mutated NSCLC patients after disease progression on a 3rd-gen EGFR TKI, with median PFS 5.8 months vs 5.4 months. 	10.1200/JCO.2025.43.16_suppl.8506
GIMR	2021-12-17	FL	3	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	Zorifertinib	Phase 1, BLOOM study. NCT02228369. N=67.	29056570
GIMR	2025-02-03	FL	3	EGFR	Exon 19 deletion, L858R, L861Q, G719	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1. U31402-A-U102 trial. N=102. In EGFR-mutated NSCLC patients who progressed after EGFR TKI and platinum-based chemotherapy, Patritumab deruxtecan showed confirmed ORR of 41% and median OS 16.2 months.	38369013
GIMR	2025-05-31	FL	3	EGFR	Exon 19 deletion, T790M, L858R, G719, L861Q, Exon 20 insertion mutations	Non-small cell lung cancer	Datopotamab Deruxtecan	Phase 2 TROPION-Lung05 trial. NCT04484142. N=137. Dato-DXd showed an ORR of 35.8% in heavily pretreated NSCLC with actionable genomic alterations, with median DOR of 7.0 months.	39761483
GIMR	2025-05-31	FL	3	EGFR	Exon 19 deletion,L858R	Non-small cell lung cancer	Patritumab deruxtecan	Phase 2 HERTHENA-Lung01 trial. NCT04619004. N=225. Patritumab Deruxtecan (HER3-DXd) showed a confirmed ORR of 29.8% with median DOR of 6.4 months, median PFS of 5.5 months, and median OS of 11.9 months in patients with EGFR-mutated NSCLC previously treated with EGFR TKI and platinum-based chemotherapy.	37689979
GIMR	2020-04-16	FL	3	EGFR	Exon 19 insertion	Non-small cell lung cancer	Erlotinib; Gefitinib	Retrospective analysis of NSCLC patients. Both EGFR exon 19 insertion and A763_Y764 insFQEA showed sensitivity to EGFR TKIs, with response rates of 56% and 73%, and median time to progression of 10.4 months and 5.0 months, respectively.	28089594
GIMR	2020-04-16	FL	3	EGFR	Exon 20 insertion	Non-small cell lung cancer	Poziotinib	ZENITH20. ORR 35% (combined EGFR and ERBB2 groups). PFS 5.5 months	10.1016/j.annonc.2020.08.2293
GIMR	2026-03-04	FL	3	EGFR	Exon 20 insertion	Non-small cell lung cancer	Sunvozertinib	Phase II dose-randomized study. WU-KONG1B. NCT03974022. Sunvozertinib 200 mg or 300 mg. N=85, 89, 107 efficacy-evaluable patients across 200 mg-rand, 300 mg-rand, and 300 mg-all cohorts. Platinum-pretreated advanced NSCLC with EGFR exon20ins. Primary endpoint cORR was 45.9% (200 mg), 47.2% (300 mg-rand), and 45.8% (300 mg-all) per IRC. Null hypothesis rejected (P < .0001). DoR 13.8 months (300 mg) versus 11.1 months (200 mg). Subgroup cORR higher in baseline brain metastasis (52.4% v 28.6%) and prior amivantamab treatment (41.7% v 25%). Establishes efficacy for platinum-pretreated EGFR exon20ins NSCLC.	40923280
GIMR	2021-06-10	FL	3	EGFR	Exon 20 insertion, A763_Y764insFQEA, V769_D770insGG, V769_D770insASV, D770_N771insG, D770_N771insGL, D770_N771insGD, D770delinsGY, N771delinsKH, N771_P772insH, P772_H773insPNP, H773_V774insNPH, V774_C775insHV	Non-small cell lung cancer	Mobocertinib	NCT02716116. Combined PPP and EXCLAIM cohort.	10.1200/JCO.2021.39.15_suppl.9014
GIMR	2021-06-08	FL	3	EGFR	Exon 20 insertion, V769_D770insASV, D770_N771insG, D770_N771insSVD, D770delinsDV, N771_P772insSVDN, H773_V774insH, H773_V774insAH, H773_V774insPHPH, V774_C775insHV	Non-small cell lung cancer	DZD9008	Phase 1 WU-KONG1/2 trials. At the RP2D dose, ORR 48% (15/31). DCR 90% (28/31).	10.1200/JCO.2021.39.15_suppl.9008
GIMR	2021-06-01	FL	3	EGFR	G719, L747S, S768I, L861Q	Non-small cell lung cancer	Osimertinib	Phase 2 KCSG-LU15-09: Osimertinib for Patients With NSCLC harboring uncommon EGFR Mutations. N=37, ORR 50%	31825714
GIMR	2026-03-04	FL	3	EGFR	G719X, L861Q, S768I, Exon 18 deletion, Exon 19 insertion, L747P, Oncogenic mutations and NOT Exon 20 insertion and NOT Exon 19 deletion and NOT L858R and NOT T790M	Non-small cell lung cancer	Afatinib	Randomized open-label study. ACHILLES/TORG1834. jRCTs031180175. N=109. Treatment-naive nonsquamous NSCLC with uncommon EGFR mutations. Afatinib significantly improved median PFS over platinum-pemetrexed chemotherapy (10.6 vs 5.7 months; HR, 0.421; P = .0010). ORR was 61.4% for afatinib versus 47.1% for chemotherapy. Median DoR favored afatinib (10.6 vs 5.6 months; HR, 0.348). OS data immature. 	40239133
GIMR	2026-03-04	FL	3	EGFR	L861R, T751_I759delinsN, Oncogenic mutation AND NOT Exon 20 insertion	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2025-05-31	FL	3	EGFR	Oncogenic mutation and NOT Exon 19 deletion and NOT L858R, Exon 20 insertion	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 69% and mPFS of 7.0 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2021-02-12	FL	3	EGFR	Oncogenic mutations, Exon 20 insertions, Exon 19 deletions, G719, G724S, G719Y, T790M, C797S, L858R, L861Q	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1. Efficacy population (N=57). ORR 39% (22/57). DCR 72%. Median DCR 6.9 months. Similar efficacy seen in prior Osimertinib population. ORR 32% (8/25) in patients with brain metastasis. Response not dependent on HER3 membrane H-scores.	34548309, 10.1200/JCO.2021.39.15_suppl.9007
GIMR	2020-04-16	FL	3	EGFR	S768I, A767_V769dup, P772dupDNP, S768_D770dup, D770insG, D770insY, H773Y, N771insH, D770delinsGY	Non-small cell lung cancer	Poziotinib	Phase 2. N=11. Poziotinib demonstrated a confirmed objective response rate of 64% in patients with NSCLC with EGFR exon 20 mutations, showing potent and clinically active inhibition of EGFR and HER2 exon 20 mutations.	29686424
GIMR	2021-06-10	FL	3	EGFR+EGFR	C797S and Exon 19 deletion, C797S and L858R, L718 and Exon 19 deletion, L718 and L858R, G724S and Exon 19 deletion, G724S and L858R, L792H and Exon 19 deletion, L792H and L858R, G796S and Exon 19 deletion, G796S and L858R, E709K and Exon 19 deletion, E709K and L858R, Amplification and Exon 19 deletion, Amplification and L858R	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 1 CHRYSALIS. Combination treatment after osimertinib relapse. Dose expansion N=45. ORR 36%. The ORR in 17/45 (47%) with EGFR or MET-based resistance mechanism identified by NGS.	10.1200/JCO.2021.39.15_suppl.9006
GIMR	2024-09-13	FL	3	EGFR+ERBB3	EGFR:Protein expression AND ERBB3:Protein expression	Solid tumours	Izalontamab brengitecan	Phase 1. NCT05194982. N=195. BL-B01D1, showed objective response rate of 34% in patients with locally advanced or metastatic solid tumours. No relationship was found between H-scores and EGFR or HER3 and response.	38823410
GIMR	2024-09-13	FL	3	EGFR+ERBB3	EGFR:Protein expression AND ERBB3:Protein expression	Urothelial carcinoma	Izalontamab brengitecan	Phase 1b/2 trial.  NCT05785039. N=32. Locally advanced or metastatic urothelial carcinoma. ORR was 44% (10/23), 35% confirmed. DCR was 91%, mPFS was 5.5 months at dose of 2.2 mg/kg.	10.1016/j.annonc.2024.08.2044 
GIMR	2021-06-10	FL	3	EGFR+MET	EGFR:Exon 19 deletion and MET:amplification, EGFR:L858R and MET:amplification, EGFR:Exon 19 deletion and MET:exon 14 skipping mutation, EGFR:L858R and MET:exon 14 skipping mutation	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 1. CHRYSALIS. Amivantamab + Lazertinib combination treatment after osimertinib relapse. In a dose expansion cohort (N=45), overall response rate (ORR) was 36%. Notably, patients with EGFR or MET-based resistance mechanisms identified by NGS demonstrated an ORR of 47% (17/45).	10.1200/JCO.2021.39.15_suppl.9006
GIMR	2020-06-23	FL	3	EGFR+MET	EGFR:Oncogenic mutations and MET:amplification	Non-small cell lung cancer	Osimertinib + Savolitinib	Phase 1b. TATTON. NCT02143466. N=186. Osimertinib + savolitinib showed acceptable risk-benefit profile and encouraging antitumour activity in MET-amplified, EGFR mutation-positive NSCLC patients who progressed on EGFR TKIs, with ORR of 48% (Part B) and 64% (Part D).	32027846, 10.1158/1538-7445.AM2019-CT032
GIMR	2024-08-27	FL	3	EGFR+MET	EGFR:Oncogenic mutations and MET:amplification	Non-small cell lung cancer	Osimertinib + Tepotinib	Phase 2. INSIGHT-2.  NCT03940703. N=128. ORR was 50% in EGFR-mutated NSCLC patients with MET amplification treated with Tepotinib and Osimertinib. Median DOR was 8.5 months. MET amplification was determined by FISH on tissue biopsy (gene copy number >=5 or MET-to-CEP7 ratio >=2) or liquid NGS (plasma gene copy number of >=2.3).	39089305
GIMR	2020-05-05	FL	3	EGFR+MET	MET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R	Non-small cell lung cancer	Capmatinib + Gefitinib	Phase 1b/2 trial. NCT01610336. N=161. Capmatinib plus gefitinib demonstrated an ORR of 27%, with enhanced activity in high MET-amplified tumors (47%), using a recommended phase II dose of capmatinib 400 mg twice daily and gefitinib 250 mg once daily.	30156984
GIMR	2020-06-11	FL	3	EGFR+MET	MET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R	Non-small cell lung cancer	Tepotinib + Gefitinib	Phase 1b/2. INSIGHT. NCT01982955. N=73. Tepotinib + gefitinib showed similar PFS (4.9 vs 4.4 months) and OS (17.3 vs 18.7 months) to chemotherapy in EGFR-mutant NSCLC with MET overexpression or amplification, but improved outcomes were seen in subgroups with high MET overexpression (PFS: 8.3 vs 4.4 months; OS: 37.3 vs 17.9 months) and MET amplification (PFS: 16.6 vs 4.2 months; OS: 37.3 vs 13.1 months).	32479794
GIMR	2020-07-10	FL	3	ERBB2	A775_G776insYVMA (Y772_A775dup), G776ins, G776R, G776C, P780_Y781insGSP (G778_P780dup), V777L	Non-small cell lung cancer	Pyrotinib	Phase 2. N=60. Previously treated NSCLC. ORR: 30%. DOR: 6.9mo. Median PFS: 6.9mo. NCT02834936	32614698
GIMR	2022-09-07	FL	3	ERBB2	A775_G776insYVMA (Y772_A775dup), M774dup	Non-small cell lung cancer	Afatinib	Global named patient use program. N=28. Heavily pretreated ERBB2 mutation-positive NSCLC. Afatinib showed activity with ORR of 19% (3/16) with DCR of 69% (11/16). Subgroup with p.A775_G776insYVMA insertion in exon 20 (N=10) had median TTF of 9.6 months, ORR of 33%, and DCR of 100%.	30096481
GIMR	2020-06-15	FL	3	ERBB2	A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup)	Solid tumours; Non-small cell lung cancer	Poziotinib	Phase 2 trial. NCT03066206. N=50. Poziotinib showed an ORR of 32% and median PFS of 5.5 months in EGFR exon 20-mutant NSCLC patients, with sensitivity influenced by insertion location (ORR: 46% near-loop vs 0% far-loop).	35820397
GIMR	2021-09-23	FL	3	ERBB2	A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, Exon 20 insertion, Exon 20 mutation	Non-small cell lung cancer	Poziotinib	Phase 2 trial. N=30. Poziotinib showed antitumor activity in patients with HER2 exon 20 mutant NSCLC with a confirmed ORR of 27%, median PFS of 5.5 months, and median OS of 15 months, despite 90% having received prior platinum-based chemotherapy.	34550757
GIMR	2026-03-04	FL	3	ERBB2	A775_G776insYVMA, D769Y	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2020-05-15	FL	3	ERBB2	Amplification	Breast cancer	Pyrotinib + Capecitabine	Randomized phase 2. ORR Pyrotinib + capecitabine was 79%. Median PFS 18.1 months.	31430226
GIMR	2020-05-04	FL	3	ERBB2	Amplification	Colorectal adenocarcinoma	Lapatinib + Trastuzumab	Phase 2 HERACLES trial. N=27. Trastuzumab + lapatinib achieved ORR of 30% (8/27) with 1 complete response and 7 partial responses in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer.	27108243
GIMR	2020-05-04	FL	3	ERBB2	Amplification	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	Phase 2 Basket trial. MyPathway. Colorectal cohort. ORR: 32% (18/57).	30857956
GIMR	2022-11-04	FL	3	ERBB2	Amplification	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	Phase 2. NCT02693535. TAPUR. N=28 in Cohort 1. ORR was 25%. DCR 54%. DOR 4.8 months	36315917
GIMR	2020-07-03	FL	3	ERBB2	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Margetuximab + Pembrolizumab	Phase 1b/2 CP-MGAH22-05 trial. NCT02689284. N=95. Margetuximab plus pembrolizumab showed acceptable safety and tolerability with an ORR of 18% (17/92) in patients with previously treated HER2-positive gastro-oesophageal adenocarcinoma.	32653053
GIMR	2025-06-09	FL	3	ERBB2	Amplification	Non-small cell lung cancer; Endometrial cancer; Salivary gland cancer	Trastuzumab deruxtecan	Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).	10.1200/JCO.2025.43.16_suppl.3020
GIMR	2021-10-12	FL	3	ERBB2	Amplification	Salivary gland cancers	Trastuzumab Emtansine	Phase 2 Basket trial. NCT02675829. N=10. ORR 90% (9/10). Median DOR and PFS not reached at follow-up of 12 months.	10.1200/JCO.2019.37.15_suppl.6001
GIMR	2022-06-04	FL	3	ERBB2	Amplification	Solid tumours	Trastuzumab + Pertuzumab	Phase 2. Basket. JRCT2031180150. N=40. ORR by BICR was 22.5%. 	10.1200/JCO.2022.40.16_suppl.3131
GIMR	2020-04-16	FL	3	ERBB2	Amplification	Uterine serous carcinoma	Carboplatin + Paclitaxel + Trastuzumab	Phase 2 trial. N=61. Median PFS was significantly longer with carboplatin-paclitaxel-trastuzumab (12.6 months) versus carboplatin-paclitaxel (8.0 months) in patients with HER2-positive advanced or recurrent uterine serous carcinoma.	29584549, 32601075
GIMR	2021-06-05	FL	3	ERBB2	Amplification, Oncogenic mutations, Overexpression	Solid tumours	Trastuzumab + Pertuzumab	Phase 2 Basket trial. MyPathway. N=258. ORR 60/258 (23%). ORR in KRAS-wild type: 26%. HER2 status determined by local testing (FISH HER2/Chr17 ratio > 2.0 or HER2 CN > 6.0 or IHC 3+). 	10.1200/JCO.2021.39.15_suppl.3004
GIMR	2021-06-06	FL	3	ERBB2	Amplification, Overexpression	Biliary tract cancer	Trastuzumab deruxtecan	JMA-IIA00423. ORR of 36% (8 of 22), DCR of 82%, median of PFS 4.4 months, and median OS of 7.1 months.	10.1200/JCO.2022.40.16_suppl.4006
GIMR	2022-04-22	FL	3	ERBB2	Amplification, Overexpression	Breast cancer	Tucatinib + Trastuzumab Emtansine	Phase 1b. NCT01983501. ORR was 47% with DOR of 6.9 months.	29955792
GIMR	2020-06-29	FL	3	ERBB2	Amplification, Overexpression	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Pembrolizumab + Trastuzumab + Oxaliplatin + Capecitabine	Phase 2 trial. NCT02954536. N=37. Pembrolizumab + trastuzumab + chemotherapy achieved primary endpoint of 6-month PFS in 70% (26/37) of HER2-positive metastatic oesophagogastric cancer patients.	32437664
GIMR	2021-10-12	FL	3	ERBB2	Amplification, Overexpression	Salivary gland cancers	Trastuzumab + Docetaxel	Phase 2. UMIN000009437. N=57. ORR: 70%. CBR: 84%. Median PFS: 8.9 months. Median OS: 39.7 months.	30452336
GIMR	2022-11-19	FL	3	ERBB2	Amplification, Overexpression	Solid tumours	Zanidatamab	Phase 1. ORR 37% (31/83). CBR 51%. DCR 75%.	10.1016/S1470-2045(22)00621-0
GIMR	2020-07-03	FL	3	ERBB2	Amplification, Overexpression, L755F, D679H, G766V	Salivary gland cancers	Trastuzumab + Pertuzumab	Phase 2a MyPathway trial. NCT02091141. N=19. Objective response rate (ORR) was 63% (12/19) in patients with advanced salivary gland carcinoma treated with targeted therapies matched to specific molecular alterations, including pertuzumab + trastuzumab for HER2 alterations, vismodegib for PTCH-1/SMO mutation, vemurafenib for BRAF V600 mutation, and atezolizumab for high tumor mutational burden.	32067683
GIMR	2021-07-01	FL	3	ERBB2	Amplification, Overexpression, Oncogenic mutations, V842I	Uterine serous carcinoma; Endometrial cancer	Trastuzumab + Pertuzumab	Phase 2. TAPUR. DCR at 16 weeks: 37%, which met the primary endpoint. Note 1 patient had ERBB3 amplification. ORR 7.1%. 	10.1200/JCO.2021.39.15_suppl.5508
GIMR	2021-06-07	FL	3	ERBB2	Amplification, Overexpression, Protein expression, Low protein expression	Breast cancer	RC48-ADC	Pooled analysis of two phase 1 studies. ORR at 2mg/kg: 43% HER2-positive, 40% in HER2-2+, and 31% in HER2 IHC 1+.	10.1200/JCO.2021.39.15_suppl.1022
GIMR	2024-06-22	FL	3	ERBB2	Amplification, Overexpression, Protein expression, Low protein expression, Oncogenic mutations	Breast cancer; Solid Tumours	SHR-A1811	Phase 1. NCT04446260. N=307. SHR-A1811 showed activity with an objective response rate of 60%in heavily pretreated HER2-expressing or mutated advanced solid tumors. Response rates were 76% in 118 HER2-positive breast cancer, 60% for HER2 low-expressing, and 46% in 98 other solid cancers.	38900984
GIMR	2021-08-04	FL	3	ERBB2	Amplification; Overexpression	Biliary tract cancers; Cholangiocarcinoma; Gallbladder cancer; Ampullary carcinoma	Trastuzumab + Pertuzumab	Phase 2. MyPathway basket trial. Trastuzumab and Pertuzumab in biliary tract cancers: ORR 9/39 (23%). DCR: 20/39 (51%). PFS 4.0 months. DOR: 10.8 months. Responders were seen in extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinomas.	34339623
GIMR	2021-11-26	FL	3	ERBB2	ERBB2:amplification	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	Phase 2. TRUMPH. HER2 amplified and RAS wildtype colorectal cancer. ORR 28% ctDNA-positive group (PFS 3.1 months) and 30% in tissue-positive group (PFS 4.0 months).	34764486
GIMR	2020-05-15	FL	3	ERBB2	ERBB2:Oncogenic mutations and NOT ERBB2:amplification	Breast cancer	Neratinib	Phase 1/2 SUMMIT trial. NCT01953926. Neratinib showed activity in breast cancer (n=​25), ORR at week 8 was 32%.	29420467
GIMR	2023-07-18	FL	3	ERBB2	Exon 20 insertion	Non-small cell lung cancer	BI-1810631	Beamion Lung 1 . NCT04886804. Preliminary data (N=22) with response seen in 10/22 NSCLC patients with exon 20 insertion, ORR 11 (46%), DCR 23/24 (96%).	36528522; JCO.2023.41.16_suppl.8545
GIMR	2021-02-12	FL	3	ERBB2	Exon 20 insertion	Non-small cell lung cancer	Poziotinib	ZENITH20. ORR 35% (combined EGFR and ERBB2 groups). PFS 5.5 months	10.1016/j.annonc.2020.08.2293
GIMR	2021-12-29	FL	3	ERBB2	Exon 20 insertion, A775_G776insYVMA (Y772_A775dup)	Non-small cell lung cancer	Tarloxotinib	Phase 2. RAIN-701 NCT03805841, Cohort B. 4/9 evaluable pts (44%) exhibited tumor reduction by RECIST and 2/9 pts experienced confirmed PR (22%).	10.1016/j.annonc.2020.08.2294
GIMR	2022-02-27	FL	3	ERBB2	Exon 20 insertion, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, V777_G778insV	Non-small cell lung cancer	Poziotinib	Phase 2. ZENITH20. N=90. In as-treated population across all lines of prior therapies, ORR was 28% (25/90), DCR was 70%, median was DOR 5.1 months and median was PFS 5.5 months.	34550757
GIMR	2021-06-10	FL	3	ERBB2	Exon 20 insertion, Exon 20 mutation	Non-small cell lung cancer	Trastuzumab + Pertuzumab + Docetaxel	Phase 2 IFCT-1703 R2D2. ORR 29% (13/45) in patients treated with at least one prior line of therapy.	35073148, 10.1200/JCO.2021.39.15_suppl.9015
GIMR	2024-07-03	FL	3	ERBB2	Exon 20 insertion, Oncogenic mutations	Non-small cell lung cancer	Sevabertinib	Phase 1/2 SOHO-01 study. NCT05099172. N=34. Sevabertinib led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months.	10.1200/JCO.2024.42.17_suppl.LBA8598
GIMR	2026-03-03	FL	3	ERBB2	Exon 20 insertions, A775_G776insYVMA, G776delinsVC, P780_Y781insGSP, G776delinsLC	Non-small cell lung cancer	Trastuzumab rezetecan	Phase 2 HORIZON-Lung trial. NCT04818333. N=94. Trastuzumab rezetecan showed significant activity with an ORR of 73% in patients with advanced HER2-mutant NSCLC. 	40020696
GIMR	2025-10-18	FL	3	ERBB2	Exon 20 insertions, A775_G776insYVMA, Tyrosine kinase domain mutations	Non-small cell lung cancer	Sevabertinib	Phase 1/2. SOHO-01. NCT05099172. N=209. Three cohorts: D (previously treated without HER2-targeted therapy) had ORR 64%, median duration 9.2 months, PFS 8.3 months; E (previously received HER2 ADCs) ORR 38% with DOR duration 8.5 months, PFS 5.5 months; F (untreated) ORR 71% , with DOR 11.0 months, PFS immature.	10.1056/NEJMoa2511065
GIMR	2025-10-18	FL	3	ERBB2	Exon 20 insertions, A775_G776insYVMA, Tyrosine kinase domain mutations	Non-small cell lung cancer	Zongertinib	Phase Ib. Beamion LUNG 1. NCT04886804. N=74. First-line zongertinib in treatment-naïve advanced HER2-mutant NSCLC showed ORR 77%, DOR 80%, PFS at 6 months 79%.	ESMO25.LBA74
GIMR	2020-05-31	FL	3	ERBB2	Kinase domain mutation	Non-small cell lung cancer	Trastuzumab deruxtecan	Phase 2 DESTINY-Lung01 trial. NCT03505710. N=42. Trastuzumab deruxtecan showed a confirmed ORR of 62% with median DOR not reached and estimated median PFS of 14.0 months in patients with HER2-mutated NSCLC, with 91% having prior platinum-based chemotherapy.	10.1200/JCO.2020.38.15_suppl.9504
GIMR	2023-06-12	FL	3	ERBB2	NOT Amplification and NOT Overexpression	Breast cancer	Patritumab deruxtecan	NCT04699630. Phase 2. N=60. In HER2-negative metastatic breast cancer, HER3-DXD resulted in ORR of 35% for all pts with CBR of 48%. Response are seen irrespective of HER3 expression status. 	10.1200/JCO.2023.41.16_suppl.1004
GIMR	2025-05-31	FL	3	ERBB2	Oncogenic mutations	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic EGFR mutations, with ORR of 53%, DCR 100%, and mPFS of 7.5 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2020-05-15	FL	3	ERBB2	Oncogenic mutations, A775_G776insYVMA (Y772_A775dup), exon 20 insertion	Non-small cell lung cancer	Pyrotinib	Phase 2 trial. NCT02535507. Pyrotinib showed significant antitumor activity against HER2 exon 20-mutated NSCLC in patient-derived organoids and xenografts, with a 53% ORR and 6.4 months median PFS in 15 patients.	30596880
GIMR	2026-03-03	FL	3	ERBB2	Oncogenic mutations, Tyrosine kinase domain mutation, A775_G776insYVMA, P780_Y781insGSP, G776delinsVC, L755P, G776V, S310F, V659E	Non-small cell lung cancer	Zongertinib	Phase 1a-1b trial. NCT04886804. Zongertinib showed clinical benefit in patients with previously treated HER2-mutant NSCLC, with ORR of 71% (Cohort 1, 120mg dose), 48% (Cohort 5), and 30% (Cohort 3); Median PFS was 12.4 months (Cohort 1)	40293180
GIMR	2020-05-04	FL	3	ERBB2	Oncogenic mutations, V659E, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G778insCPG, G776delinsVC, exon 20 insertion	Non-small cell lung cancer	Trastuzumab Emtansine	Phase 2 trials. Trastuzumab emtansine (T-DM1) showed activity in patients with HER2-overexpressing (IHC 3+) NSCLC and HER2-mutant lung cancers, with overall response rates of 20% and 44% respectively, with responses associated with HER2 gene amplification in the HER2-overexpressing cohort.	30206164, 29989854
GIMR	2025-05-31	FL	3	ERBB2	Overexpression	Colorectal adenocarcinoma	TQB2102	Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed  anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)	10.1200/JCO.2025.43.16_suppl.3002
GIMR	2025-05-31	FL	3	ERBB2	Overexpression	Gastric cancer	TQB2102	Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed  anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)	10.1200/JCO.2025.43.16_suppl.3002
GIMR	2020-07-21	FL	3	ERBB2	Overexpression	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Trastuzumab Emtansine	ORR 20% GATSBY trial, but failed in P3 against docetaxel	28343975
GIMR	2025-06-09	FL	3	ERBB2	Overexpression	Gastroesophageal junction adenocarcinoma; Gastric Cancer; Colorectal adenocarcinoma	JSKN003	Pooled analysis of JSKN003-101 and JSKN003-102 trials. NCT05494918, NCT05744427. N=40. JSKN003 showed activity in heavily pretreated patients with advanced HER2-overexpressing gastrointestinal tumors, with ORR of 67% and median PFS of 9.6 months.	10.1200/JCO.2025.43.16_suppl.3022
GIMR	2025-05-31	FL	3	ERBB2	Overexpression	Solid tumours	TQB2102	Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed  anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)	10.1200/JCO.2025.43.16_suppl.3002
GIMR	2025-01-13	FL	3	ERBB2	Overexpression, Amplification	Breast cancer	Neratinib + Trastuzumab emtansine	Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + Trastuzumab Emtansine achieved 33.3%-35.3% CNS ORR in HER2+ breast cancer brain metastases, with median OS of 20.9-30.2 months across three cohorts.	38977064
GIMR	2023-01-20	FL	3	ERBB2	Overexpression, Protein expression, Amplification	Solid tumours	IMU-131	Phase 1b Trial IMU.ACS.001. NCT02795988. Objective response seen in 5 of 14 patients.	33879458
GIMR	2025-07-02	FL	3	ERBB2	Overexpression, Protein expression, Low protein expression	Breast cancer; Urothelial carcinoma	Trastuzumab + Nivolumab	Phase Ib. DS8201-A-U105. NCT03523572. N=82. T-DXd (5.4 mg/kg) plus nivolumab 360 mg every 3 weeks showed confirmed objective response rates (cORR) of 65.6% (HER2-positive mBC, cohort 1), 50.0% (HER2-low mBC, cohort 2), and 36.7% (HER2-high mUC who had received prior platinum-based chemotherapy, cohort 3). Median PFS was 11.6 months (cohort 1), 7.0 months (cohort 2), and 6.9 months (cohort 3). Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 20.7% (cohort 1) and 20.0% (cohort 3). In Cohort 4 (n=4, HER2-low advanced urothelial cancer/mUC), 2 responders were also seen. Safety consistent with T-DXd monotherapy, though higher TEAE discontinuation rates observed.	39405343
GIMR	2025-01-09	FL	3	ERBB2	Overexpression, Protein expression, Low protein expression	Urothelial carcinoma	Disitamab vedotin + Toripalimab	Phase 1b/2 RC48-C014 trial. N=41. In locally advanced or metastatic urothelial carcinoma patients, disitamab vedotin + toripalimab showed confirmed ORR of 73%, median PFS of 9.3 months, and median OS of 33.1 months. The study was HER2-unselected, and responders were seen in HER2 1+/2+/3+ populations.	39662628
GIMR	2025-05-31	FL	3	ERBB2	Overexpression, Protein expression, Low-protein expression	Breast cancer	TQB2102	Phase1 trial. TQB2102. N=181. TQB2102, a bispecific anti-HER2 antibody-drug conjugate, was well-tolerated with no dose-limiting toxicities and showed  anti-tumor activity with an ORR of 41.2% in patients with advanced solid tumors, including HER2-positive (ORR 52%), HER2-low metastatic breast cancer (ORR 47%), HER2 overexpressed colorectal cancer (ORR 44%), HER2-positive gastric cancer (ORR 40%)	10.1200/JCO.2025.43.16_suppl.3002
GIMR	2020-06-13	FL	3	ERBB2	P780_Y781insGSP (G778_P780dup)	Non-small cell lung cancer	Afatinib; Dacomitinib; Pyrotinib; Poziotinib	Preclinical study. Structural modeling and molecular dynamics simulations revealed that HER2 ex20ins mutants with shorter alphaC-beta4 loop, such as G778_P780dup, had higher affinity to TKIs like afatinib and sustained tumor responses were observed in patients treated with these inhibitors.	32036069
GIMR	2021-03-08	FL	3	ERBB2	P780_Y781insGSP (G778_P780dup)	Non-small cell lung cancer	Dacomitinib	Phase 2 trial: 2/2 patients harbouring the mutation responded to Dacomitinib with prolonged response.	25899785
GIMR	2020-10-05	FL	3	ERBB2	Protein expression and NOT amplification	Breast cancer	Trastuzumab deruxtecan	Phase 1b study. NCT02564900. DESTINY-Breast04. N=54. Trastuzumab deruxtecan showed an ORR of 37.0% with median DOR of 10.4 months in patients with HER2-low-expressing advanced breast cancer.	32058843
GIMR	2023-03-20	FL	3	ERBB2	protein expression and NOT amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma	Trastuzumab deruxtecan	Phase 2. DESTINY-Gastric01. NCT03329690. Confirmed ORR 26% (5/19, cohort 1, ISH-negative, IHC 2+) and 10%(2/21, cohort 2, IHC 1+). 13 (68%, cohort 1) and 12 (60%, cohort 2) experienced reduced tumor size. Median OS was 7.8 months (Cohort 1) and 8.5 months (Cohort 2). Median PFS 4.4 (Cohort 1) and 2.8 months (Cohort 2).	36379002
GIMR	2024-05-14	FL	3	ERBB2	Protein expression AND NOT Oncogenic mutations, Overexpression AND NOT Oncogenic mutations	Non-small cell lung cancer	Trastuzumab deruxtecan	Phase 2. NCT03505710. DESTINY-Lung01. Confirmed ORR 27% (N=49, Cohort 1) and 34 (N=41, Cohort 1A) respectively.	38547891
GIMR	2023-03-29	FL	3	ERBB2	Protein expression, Low protein expression	Uterine carcinosarcoma	Trastuzumab deruxtecan	NCCH1615/STATICE. Phase 2. Single-arm. ORR were 55% (12/22) in HER2-high and 70% (7/10) in HER2-low group. Median PFS were 6.9 and 8.1 months respectively. HER2-low status is defined as IHC 1+/2+. HER2-High is defined as IHC 3+.	36977309
GIMR	2022-11-25	FL	3	ERBB2	Protein expression, Protein expression NOT amplification	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Trastuzumab deruxtecan	DESTINY-Gastric 01. NCT03329690. Exploratory cohort. In IHC 2+ / ISH negative cohort, ORR was 26% (5/19), meeting the prespecified endpoint. DCR 90%. 	36379002
GIMR	2024-05-08	FL	3	ERBB2	S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, A775_G776insYVMA (Y772_A775dup), L755S, P780_Y781insGSP (G778_P780dup), T862A, V842I	Solid tumours	Trastuzumab deruxtecan	Phase 2. DESTINY-PanTumor01. NCT04639219. N=102. Trastuzumab deruxtecan showed anti-tumour activity and durable responses in heavily pretreated patients across multiple tumour types with activating HER2 mutations. The ORR was 29%.	38710187
GIMR	2020-06-13	FL	3	ERBB2	S310F, S310Y, L755S, A775_G776insYVMA (Y772_A775dup), V777L, P780_Y781insGSP (G778_P780dup), L869R	Breast cancer	Fulvestrant + Neratinib	Phase 2 SUMMIT trial. NCT01953926. N=81. Neratinib showed activity in HER2-mutant metastatic breast cancer with ORR of 17.4% and 36.4% in ER+ and ER- patients on monotherapy, and 29.8% in ER+ patients on combination with fulvestrant; median PFS was 3.6, 2.0, and 5.4 months respectively.	31806627
GIMR	2025-05-24	FL	3	ERBB2	Tyrosine kinase domain mutation, A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776delinsVC, L755P, G776V	Non-small cell lung cancer	Zongertinib	Phase 1a/b trial. NCT04886804. Zongertinib demonstrated clinical benefit in HER2-mutant NSCLC patients, with objective response rates of 71% (120mg dose), 48% (Cohort 5), and 30% (Cohort 3), and a median PFS of 12.4 months.	40293180
GIMR	2026-03-03	FL	3	ERBB2+ESR1	ESR1:Protein expression AND ERBB2:Amplification, ESR1:Protein expression AND ERBB2:Overexpression	Breast cancer	Zanidatamab + Palbociclib + Fulvestrant	Phase 2a study. NCT04224272. N=51. Zanidatamab plus palbociclib and fulvestrant showed promising antitumour activity with PFS at 6 months being 66.7% in heavily pretreated hormone receptor-positive, HER2-positive metastatic breast cancer patients. Most common adverse events were diarrhoea (80%) and neutropenia (51%).	40339592
GIMR	2025-07-30	FL	3	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Gedatolisib + Palbociclib + Letrozole; Gedatolisib + Palbociclib + Fulvestrant	Phase 1b. Dose expansion groups of NCT02684032. N=103. ORR was 85.2% in first-line group A, 61.5% in group B, 25.0% in group C, and 55.6% in group D. Adverse events: neutropenia (63%), stomatitis (27%), rash (20%), and hyperglycaemia (6%). No treatment-related deaths. Responses observed in both wild-type and mutated PIK3CA tumours.	38547892
GIMR	2024-01-31	FL	3	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	PF-07104091	Phase 1, NCT04553133. In 16 RECIST evaluable HR+/HER2- metastatic breast cancer, ORR was 19% (n=3). DCR was 62%.	10.1200/JCO.2023.41.16_suppl.3010
GIMR	2024-01-31	FL	3	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	PF-07220060	Phase 1/2a study. PF-07220060 alone or with endocrine therapy in HR+/HER2- metastatic breast cancer with prior endocrine therapy and CDK4/6 inhibitors exposure. ORR was 29%. Median PFS of 25 weeks.	10.1200/JCO.2023.41.16_suppl.3009
GIMR	2020-05-30	FL	3	ERBB2+KRAS	ERBB2:Amplification and ERBB2:Protein expression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E, ERBB2:Overexpression and NOT KRAS:Oncogenic mutations and NOT BRAF:V600E	Colorectal adenocarcinoma	Trastuzumab deruxtecan	Phase 2 DESTINY-CRC01. ORR 45% (24/53) in HER2-positive (Cohort A, IHC 3+ or IHC2+ and ISH-positive) population.	33961795, 10.1200/JCO.2020.38.15_suppl.4000, 10.1200/JCO.2021.39.15_suppl.3505
GIMR	2022-06-06	FL	3	ERBB3	Protein expression	Breast cancer	Patritumab deruxtecan	NCT02980341. In heavily pretreated metastatic breast cancer, Patritumab deruxtecan showed ORR of 30% in Hormone receptor-positive / HER2-negative MBC, 22% in metastic TNBC, and 43% in metastatic HER2-positive metatatic breast cancer. Median duration of response were 7.2, 5.9, and 8.3 months, respectively.	10.1200/JCO.2022.40.16_suppl.1002
GIMR	2021-06-08	FL	3	ESR1	E380Q, S463P, V422del, L536P, L536H, Y537C, Y537D, Y537N, Y537S, D538G	Breast cancer	Camizestrant	Phase 1. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44).	38729567
GIMR	2021-02-02	FL	3	ESR1	Protein expression	Breast cancer	Elacestrant	Phase 1. N=50 with ORR 19%. 52% treated with prior SERD. 	33513026
GIMR	2025-06-24	FL	3	ESR1	Protein expression	Endometrial cancer	Fulvestrant + Abemaciclib	Phase 2 study. N=27. Fulvestrant plus Abemaciclib showed promising activity in hormone receptor-positive advanced or recurrent endometrial cancer with an ORR of 44% and median PFS of 9.0 months, with durable responses observed mainly in copy number-low/no specific molecular profile tumors.	39561275
POTTR	2020-04-16	FL	3	ESR1	Protein expression	Endometrial cancer	Tamoxifen + Medroxyprogesterone Acetate; Fulvestrant; Exemestane; Everolimus + Letrozole	Systematic review	31134155
GIMR	2021-07-01	FL	3	ESR1	Protein expression	Endometrial cancer	Vistusertib + Anastrozole	Randomized phase 2: VICTORIA. N=73. In ER/PR-positive endometrial carcinoma, progression-free rate at 8 weeks was 67% vs 39%. ORR: 25% (combination) vs 17.4% (anastrozole alone).	10.1200/JCO.2021.39.15_suppl.5507
GIMR	2020-09-21	FL	3	ESR1	Protein expression	Endometrioid endometrial cancer; Endometrial cancer	Palbociclib + Letrozole	ESMO 2020 LBA28. NSGO-PALEO / ENGOT-EN3	10.1016/j.annonc.2020.08.2258
GIMR	2026-03-04	FL	3	ESR1	Protein expression	Low-grade serous ovarian cancer	Ribociclib + Letrozole	Phase 2 GOG 3026 trial. NCT03673124. N=49. Confirmed ORR was 30.6% with 1 complete and 14 partial responses. Median duration of response was 21.2 months. CBR was 84%. Median PFS was 14.5 months. Median OS was 44.5 months. ER not explicity required into the trial but >=95% of LGSOC are expected to have ER positivity.	41385758
GIMR	2021-06-08	FL	3	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Camizestrant	Phase 1. SERENA-1. NCT03616587. N=108. Across all dose levels, camizestrant showed ORR of 15% (13/85), and CBR at 24 weeks of 35% (38/108), in heavily pre-treated patients with metastatic ER-positive, HER2-negative breast cancer. In patients with ESR1 mutation at baseline, ORR was 27% (12/44).	38729567
GIMR	2026-03-04	FL	3	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Camizestrant	Phase 2 SERENA-3 trial. N=132. Camizestrant reduced ER expression by approximately 65% for all doses. Greater reduction in Ki67 expression was seen after 12-15 days compared to 5-7 days. Maximal effects on ER and Ki67 expression were achieved with camizestrant 75 mg once daily.	41628308
GIMR	2023-10-02	FL	3	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	ARV-471	Phase 1/2 study (VERITAC). NCT04072952. In ARV-471 monotherapy for ER+/HER2- metastatic breast cancer, CBR was 40% at 24 weeks and independent of ESR1 mutation (including 3 PR). All patients received prior CDK4/6 inhibitors, and majority received prior fulvestrant and prior chemotherapy.	10.1158/1538-7445.SABCS22-GS3-03
GIMR	2024-09-09	FL	3	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression; ESR1:Protein expression and ESR1:oncogenic mutations and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Imlunestrant	Phase 1a/Ib EMBER study. NCT04188548. N=262. Imlunestrant showed manageable safety profile and preliminary antitumor activity in ER+/HER2- advanced breast cancer, with median PFS of 7.2 months (monotherapy) and up to 19.2 months (in combination with targeted therapy).	39241211
GIMR	2026-03-06	FL	3	ESR1+ERBB2+BRCA1	Oncogenic mutations	Breast cancer	Avelumab + Talazoparib	Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 34.8% in HR-positive, ERBB2-negative, DDR-positive BC (n=23, median PFS 5.3 months, DOR 15.7 months)Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials.	36394849
GIMR	2026-03-06	FL	3	ESR1+ERBB2+BRCA2	Oncogenic mutations	Breast cancer	Avelumab + Talazoparib	Phase 1b/2 basket trial. JAVELIN PARP Medley. NCT03330405. Avelumab plus talazoparib ORR was 34.8% in HR-positive, ERBB2-negative, DDR-positive BC (n=23, median PFS 5.3 months, DOR 15.7 months)Prolonged DOR in specific subtypes warrant further investigation in randomized clinical trials.	36394849
GIMR	2020-12-30	FL	3	EZH2	Y646F, Y646N, Y646S, Y646H, Y646C, A682G, A692V	Follicular lymphoma	Tazemetostat	Single-arm study in relapsed or refractory disease. ORR 69% in EZH2 mutant group (vs 35% in wildtype). EZH2 hotspot oncogenic mutation.	33035457
GIMR	2021-12-17	FL	3	FGFR1	Amplification	Breast cancer	Lucitanib	Phase 2. FINESSE. NCT02053636. In HR+/HER2− metastatic breast cancer, ORR was 19% in the FGFR1-amplified cohort (defined as gene/centromere ratio ≥2 or average copy number ≥6).	31619444
GIMR	2023-05-05	FL	3	FGFR1	Fusion	Endometrial cancer	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2024-04-13	FL	3	FGFR1	Fusion; FGFR1-TACC1 fusion	Solid tumour	Erdafitinib	Phase 2. NCI-MATCH. EAY131-K2 trial. NCT03198147. N=35. Erdafitinib showed antitumor efficacy in patients with FGFR1-4 mutations or fusions with ORR of 16% (4/25) and Median PFS of 3.6 months. 	38603650
GIMR	2022-10-20	FL	3	FGFR1	High mRNA expression	Urothelial carcinoma	Rogaratinib	NCT03410693. Randomised Phase 2. FORT-1. FGFR1/3 mRNA positive population. N=87 in the Rogaratinib group. ORR was 21% (18/87), and median OS was 8.3 months. However, neither ORR or OS was superior to chemotherapy group. 	36240478
GIMR	2023-05-05	FL	3	FGFR1	K656E	Diffuse astrocytoma	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2024-07-19	FL	3	FGFR1	K656E	Glioblastoma	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months.	38710951
GIMR	2021-06-12	FL	3	FGFR1	Oncogenic mutations	Solid tumours	Erdafitinib	Phase 2. RAGNAR. NCT04083976. Across FGFR1-3 alterations (mutations and fusions) treated with erdafitinib, ORR was 29% (52/178, including 3 CR) by independent review committee, DCR was 73% (129/178). Median DOR 7.1 months. PFS 5.2 months. OS 10.9 months. ORR was comparable with FGFR mutations vs fusions (26-27%).	10.1200/JCO.2022.40.16_suppl.3007
GIMR	2023-05-05	FL	3	FGFR2	C382R (G380R)	Cervical cancer	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2023-05-05	FL	3	FGFR2	C382R (G380R), I291_Y308del, Extracellular domain deletion, Y375C, W290C	Cholangiocarcinoma	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2022-07-26	FL	3	FGFR2	C382R (G380R), W290C	Cholangiocarcinoma	Futibatinib	NCT02052778. TAS-120-101. Phase 1 dose expansion. Responders seen in cholangiocarcinoma (1 patient each) harbouring C383R and W290C. 	34551969
GIMR	2022-10-07	FL	3	FGFR2	Fusion	Cholangiocarcinoma	Derazantinib	Phase 2. FIDES-01. NCT03230318. In patients with intrahepatic cholangiocarcinoma harbouring a FGFR2 fusion (N=143), ORR was 21%, DCR was 76%. Median OS was 17.2 months and PFS was 8.0 months.	10.1016/j.annonc.2022.07.087
GIMR	2022-10-12	FL	3	FGFR2	Fusion	Cholangiocarcinoma	Lirafugratinib	Phase 1. ReFOCUS. ORR was 63% (24/38); 88% (15/17) at RP2D with DCR 100%.	10.1016/j.annonc.2022.08.006
GIMR	2023-05-05	FL	3	FGFR2	Fusion	Ovarian cancer; Pancreatic adenocarcinoma; Cervical cancer; Non-small cell lung cancer; Prostate cancer	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2023-07-08	FL	3	FGFR2	Fusion, C382R, R678H, H167_N173del, C383R, W290C	Cholangiocarcinoma	Lirafugratinib	Phase 1/2.ReFocus. NCT04526106. ORR in FGFR2-Mutated cholangiocarcinoma was 29%. In the cohort with an FGFR2 fusion and a dosage of 70mg or higher, the ORR was 73% (8/11). In FGFRi refractory CCA, the ORR was 21% (3/14).	10.1200/JCO.2023.41.16_suppl.4009
GIMR	2022-02-21	FL	3	FGFR2	Fusion, FGFR2-BICC1 fusion, FGFR2-CCDC6 fusion, FGFR2-CLIP1 fusion, FGFR2-USP33	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In FGFR fusion/rearragement cohort (N=20), ORR was 25% (5/20). 	35176457
GIMR	2024-07-19	FL	3	FGFR2	Fusion, FGFR2-BICC1 fusion, FGFR2-RBM20 fusion, FGFR2-MRVI1 fusion, FGFR2-CROCC fusion, FGFR2-KIAA1598 fusion, FGFR2 I291_Y308del, FGFR2 W290C, FGFR2 Y375C, FGFR2 C382R	Cholangiocarcinoma	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months.	38710951
GIMR	2020-06-11	FL	3	FGFR2	Fusions	Cholangiocarcinoma	Erdafitinib	Phase 2a study. LUC2001. NCT02699606. Erdafitinib showed encouraging efficacy in Asian advanced cholangiocarcinoma patients with FGFR alterations, with an ORR of 50% (60% in FGFR2-alteration positive patients) and median PFS of 5.6 months (12.4 months in FGFR2-alteration positive patients).	10.1200/JCO.2019.37.15_suppl.4117
GIMR	2021-06-12	FL	3	FGFR2	Fusions, Oncogenic mutations	Solid tumours	Erdafitinib	Phase 2. RAGNAR. NCT04083976. Across FGFR1-3 alterations (mutations and fusions) treated with erdafitinib, ORR was 29% (52/178, including 3 CR) by independent review committee, DCR was 73% (129/178). Median DOR 7.1 months. PFS 5.2 months. OS 10.9 months. ORR was comparable with FGFR mutations vs fusions (26-27%).	10.1200/JCO.2022.40.16_suppl.3007
GIMR	2024-04-13	FL	3	FGFR2	S252W; Fusion; FGFR2-ACOT11 fusion; FGFR2-AHCYL1 fusion; FGFR2-FOXP1 fusion; FGFR2-BICC1 fusion; 	Solid tumour	Erdafitinib	Phase 2. NCI-MATCH. EAY131-K2 trial. NCT03198147. N=35. Erdafitinib showed antitumor efficacy in patients with FGFR1-4 mutations or fusions with ORR of 16% (4/25) and Median PFS of 3.6 months. 	38603650
GIMR	2024-07-19	FL	3	FGFR2 	C382R (G380R)	Cervical cancer; Endometrial cancer	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months.	38710951
GIMR	2024-07-19	FL	3	FGFR3	FGFR3-TACC3 fusion, Y375C (Y373C)	Urothelial carcinoma; Glioblastoma; Cervical cancer; Endometrial cancer	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months.	38710951
GIMR	2023-05-05	FL	3	FGFR3	Fusion	Glioblastoma; Cervical cancer	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2024-07-19	FL	3	FGFR3	Fusion, FGFR3-TACC3 fusion	Cervical cancer; Endometrial cancer	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. N=107. Pemigatinib achieved ORRs of 27% (fusions,n=49), 9.4% (actionable SNV, n=32), and 3.8% (kinase domain mutations, n=26); median PFS was 4.5 and 3.7 months, and OS was 17.5 and 11.4 months.	38710951
GIMR	2025-02-06	FL	3	FGFR3	Fusion, R248C, S249C, S764fs*6, G372C (G370C), S373C (S371C), Y373C (Y375C)	Urothelial carcinoma	Pemigatinib	Phase 2. FIGHT-201. NCT02872714. N=260. Pemigatinib showed ORR of 17.8% and 23.3% in cohorts A-CD and A-ID respectively, with median DOR of 6.2 months, PFS of 4.0/4.3 months, and OS of 6.8/8.9 months in FGFR3-altered metastatic or surgically unresectable urothelial carcinoma.	37956738
GIMR	2020-05-31	FL	3	FGFR3	Fusions, FGFR3-TACC3 fusion, Oncogenic mutations, R248C, S249C, Y375C, Y373C, G370C, F386L, K650E	Urothelial carcinoma	Infigratinib	Phase 1/2 trial. N=67. BGJ398 showed an ORR of 25% and DCR of 64% in patients with advanced urothelial carcinoma with FGFR3 alterations, with a median PFS of 3.8 months and median OS of 7.8 months.	29848605, 10.1200/JCO.2019.37.15_suppl.4510
GIMR	2021-06-12	FL	3	FGFR3	Fusions, Oncogenic mutations	Solid tumours	Erdafitinib	Phase 2. RAGNAR. NCT04083976. Across FGFR1-3 alterations (mutations and fusions) treated with erdafitinib, ORR was 29% (52/178, including 3 CR) by independent review committee, DCR was 73% (129/178). Median DOR 7.1 months. PFS 5.2 months. OS 10.9 months. ORR was comparable with FGFR mutations vs fusions (26-27%).	10.1200/JCO.2022.40.16_suppl.3007
GIMR	2022-10-20	FL	3	FGFR3	High mRNA expression	Urothelial carcinoma	Rogaratinib	Randomised Phase 2. FORT-1. NCT03410693. In the FGFR1/3 mRNA positive population (N=87), rogaratinib demonstrated an ORR of 21% (18/87) and median OS of 8.3 months, which was not superior to chemotherapy.	36240478
GIMR	2026-03-04	FL	3	FGFR3	S249C, R248C, Y373C, G370C, Fusions, FGFR3-TACC3 fusion	Urothelial carcinoma	Erdafitinib; Erdafitinib + Cetrelimab	Phase 2 NORSE trial. NCT03473743. N=87. Erdafitinib monotherapy had an ORR of 44.2% with median DOR of 9.7 months, PFS of 5.6 months, and OS of 16.2 months. Erdafitinib plus cetrelimab had an ORR of 54.5% with median DOR of 11.1 months, PFS of 11.0 months, and OS of 20.8 months.	41538748
GIMR	2025-02-06	FL	3	FGFR3	S249C, Y375C (Y373C), R248C, G372C (G370C), R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusion	Urothelial carcinoma	Erdafitinib	Phase 3. THOR trial. NCT03390504. N=351. Erdafitinib did not improve OS over pembrolizumab (10.9 vs 11.1 months) in anti-PD-L1-naive patients with metastatic urothelial cancer and selected FGFR alterations, but had a higher ORR (40% vs 21.6%) and longer PFS (4.4 vs 2.7 months).	37871702
GIMR	2024-04-13	FL	3	FGFR3	S249C; Fusion; FGFR3-TACC3 fusion	Solid tumour	Erdafitinib	Phase 2. NCI-MATCH. EAY131-K2 trial. NCT03198147. N=35. Erdafitinib showed antitumor efficacy in patients with FGFR1-4 mutations or fusions with ORR of 16% (4/25) and Median PFS of 3.6 months. 	38603650
GIMR	2023-05-05	FL	3	FGFR3	Y375C (Y373C)	Urothelial carcinoma	Pemigatinib	Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%.	10.1158/1538-7445.AM2023-CT016
GIMR	2020-06-13	FL	3	FH	Loss-of-function mutations (germline)	Papillary renal cell carcinoma	Bevacizumab + erlotinib	Phase 2 study. NCT01130519. N=83. Bevacizumab + Erlotinib showed an ORR of 51% (HLRCC cohort: 64%, sporadic cohort: 37%) and median PFS of 14.2 months (HLRCC cohort: 21.1 months, sporadic cohort: 8.7 months) in advanced papillary renal cell carcinoma.	10.1200/JCO.2020.38.15_suppl.5004
GIMR	2020-10-05	FL	3	FLT3	Internal tandem duplication	Acute myeloid leukaemia	Sorafenib	Phase 2 SORMAIN trial. DRKS00000591. N=83. Sorafenib maintenance therapy significantly improved RFS (HR, 0.39) and 24-month RFS probability (85.0% vs 53.3%) compared to placebo in FLT3-ITD-positive AML patients after allogeneic HCT.	32673171
GIMR	2020-04-16	FL	3	FLT3	Internal tandem duplication	Acute myeloid leukaemia	Sorafenib	Phase 2. N=13. Sorafenib treatment in FLT3-ITD AML patients showed initial response with clearance of bone marrow myeloblasts in 12 patients, but subsequent nonresponsiveness emerged due to expansion of LICs bearing D835 mutation.	22368270
GIMR	2026-03-04	FL	3	FLT3	NOT Internal tandem duplication	Acute myeloid leukaemia	Quizartinib	Phase 2 QUIWI trial. NCT04107727. N=273. Quizartinib significantly improved EFS (20.4 vs 9.9 months) and OS (not reached vs 29.3 months) compared to placebo in patients with FLT3-ITD-negative AML, with 3-year OS rates of 60.8% vs 45.7%.	41082703, 41325561
GIMR	2021-07-11	FL	3	FOLR1	Overexpression	Ovarian cancer	Mirvetuximab soravtansine	Phase 3. FORWARD I. In patient with platinum-resistant ovarian cancer, mirvetuximab soravtansine did improvement in PFS compared with chemotherapy versus chemotherapy in patients. In exploratory analysis, however, ORR (24% vs 10%), CA-125 response, as well as PFS and OS improvement over chemotherapy were seen in FR alpha-high subgroup (N=147).	33667670
GIMR	2024-09-07	FL	3	FOLR1	Protein expression	Ovarian cancer	Luveltamab tazevibulin	Phase 1. Dose expansion cohort of STRO-002-GM1. NCT03748186. N=44. Luveltamab tazevibulin showed activity (ORR 12 of 32, 38%) in recurrent epithelial ovarian cancer with FolRα expression as low as TPS>25%. 	10.1200/JCO.2023.41.16_suppl.5508
GIMR	2021-07-01	FL	3	FOLR1	Protein expression	Ovarian cancer	Mirvetuximab soravtansine + Bevacizumab	Phase 1b FORWARD II trial. N=60. ORR 47%. In patients with high FR expression, confirmed ORR was 64%. In platinum-resistance disease with high FR expression, ORR was 59%. Median PFS 10.1 months.	10.1200/JCO.2021.39.15_suppl.5504
GIMR	2025-01-09	FL	3	FOLR1	Protein expression, Overexpression	Ovarian cancer	Mirvetuximab soravtansine	Phase 2. PICCOLO trial. NCT05041257. N=79. Mirvetuximab soravtansine showed ORR of 51.9% and median DOR of 8.25 months in FRalpha-positive, third-line or later, recurrent platinum-sensitive ovarian cancer. Positive FRα expression was defined as 75% of cells with 2+ staining intensity, assessed using the VENTANA FOLR1 RxDx Assay on either a fresh/recent biopsy or archival tumour tissue.	39617145
GIMR	2024-10-24	FL	3	GNAS	Oncogenic mutations	Peritoneal mucinous carcinomatosis	Palbociclib	Phase 2. N=16. Palbociclib showed clinical activity in GNAS-mutant peritoneal mucinous carcinomatosis. SD was observed in 50% of evaluable patients after 12 months. Median OS was not reached at a median follow-up of 17.6 months.	39413348
GIMR	2021-06-15	FL	3	HGF	Amplification	Papillary renal cell carcinoma	Durvalumab + Savolitinib	Phase 2 CALYPSO: MET-driven PRCC. ORR 57% (8/14) 	10.1200/JCO.2021.39.15_suppl.4511
GIMR	2022-06-15	FL	3	HLA-A2	A*02:01	Melanoma	Tebentafusp; Tebentafusp + Durvalumab; Tebentafusp + Durvalumab + Tremelimumab	IMCgp100-201 and IMCgp100-202. PD-1 resistant or refractory cutaneous melanoma. N=230. ORR by RECIST was 10% (IMCgp100-201) and 12% (IMCgp100-202) respectively. The 1 year OS rate of tebentafusp and durvalumab combination was 73%.	10.1200/JCO.2022.40.16_suppl.104
GIMR	2021-06-28	FL	3	Homologous Recombination Deficiency Score	High	Ovarian cancer	Ceralasertib + Olaparib	Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).	10.1200/JCO.2021.39.15_suppl.5516
GIMR	2021-06-21	FL	3	HPV genotype	HPV16-positive	HPV16-positive cancers; Cervical cancer; Anal cancer; Head and neck squamous cell carcinoma; Vulvar cancer; Vaginal cancer	PDS0101 + M9241 + Bintrafusp alpha	NCT04287868. ORR 56%. ORR 42% (N=5/12) in checkpoint inhibitor refractory disease. HPV16 genotyping determined by PCR-based assay.	10.1200/JCO.2021.39.15_suppl.2501
GIMR	2020-05-31	FL	3	HRAS	Oncogenic mutations	Head and neck squamous cell carcinoma ; Salivary gland cancers; Urothelial carcinoma	Tipifarnib	Single arm Phase 2 of Tipifarnib in R/M HNSCC patients. ORR 55%. mPFS tipifarnib: 5.6 months. KO-TIP-001	33750196, 10.1200/JCO.2020.38.15_suppl.6504
GIMR	2023-11-14	FL	3	HRAS	Oncogenic mutations, G12C, G12D, G12S, G13R, G13V	Head and neck squamous cell carcinoma	Tipifarnib	Kura data set (NCT02383927) showed median DFS of 4.0 months (range 1-63 months, n=27), and OS of 25.5 months (range 4-94 month, n=27). Median OSmet was 15.0 months (range 1-47 months, n=27). MDACC data set showed median DFS of 4.0 months (n=12), and OS of 15 months (n=12). Median OSmet was 12 months (n=12).	36603172
GIMR	2020-09-21	FL	3	IDH1	Oncogenic mutations	Acute myeloid leukaemia	Azacitidine + Venetoclax	Exploratory biomarker subgroup in Ph3 VIALE-A. OS HR 0.34 vs Azacitidine alone	32786187
GIMR	2021-02-02	FL	3	IDH1	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib + Azacitidine	Phase Ib trial. NCT02677922. N=23. Ivosidenib plus azacitidine in newly diagnosed mIDH1 AML patients ineligible for intensive induction chemotherapy demonstrated an ORR of 78%, CR rate of 61%, 12-month OS of 82%, and was well tolerated.	33119479
GIMR	2023-05-05	FL	3	IDH1	R132	Acute myeloid leukaemia	LY3410738	Phase 1. NCT04603001. Dose escalation IDH1/2m R/R AML. Responses were observed in both IDH1m and IDH2m AML	10.1158/1538-7445.AM2023-CT026
GIMR	2021-03-19	FL	3	IDH1	R132C, R132S, R132	Chondrosarcoma	Olaparib	Phase 2 Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified.	34994649
GIMR	2021-06-04	FL	3	IDH1	R132H, Oncogenic mutations	High-grade gliomas; Anaplastic astrocytoma; Glioblastoma	Olaparib	Phase 2 OLAGLI. In heavily pretreated recurrent high-grade glioma, single-agent olaparib resulted in ORR 5% and  CBR 31% at 6 months. DOR 9 months.	10.1200/JCO.2021.39.15_suppl.2007
GIMR	2020-09-21	FL	3	IDH2	Oncogenic mutations	Acute myeloid leukaemia	Azacitidine + Venetoclax	Exploratory biomarker subgroup in Ph3 VIALE-A. OS HR 0.34 vs Azacitidine alone	32786187
GIMR	2021-11-04	FL	3	IDH2	R140, R172	Acute myeloid leukaemia	Enasidenib + Azacitidine	AG221-AML-005. ORR was 50/68 (74%) in the the enasidenib group versus 12/33 (36%) in the azacitidine group.	34672961
GIMR	2021-10-06	FL	3	IDH2	R140Q, R172K, R172	Myelodysplastic syndrome	Enasidenib	Phase 1/2. AG221-C-001.  ORR 9/17 (53%). Median DOR 9.2 months. Median OS 16.9 months.	32145771
GIMR	2023-05-05	FL	3	IDH2	R172, R140	Acute myeloid leukaemia	LY3410738	Phase 1. NCT04603001. Dose escalation IDH1/2m R/R AML. Responses were observed in both IDH1m and IDH2m AML	10.1158/1538-7445.AM2023-CT026
GIMR	2021-03-19	FL	3	IDH2	V305M	Epithelioid haemangioendothelioma	Olaparib	Phase 2 Basket trial. Olaparib for IDH mutations: 1/10 (10%) with PR lasting 14 months. CBR at 16 weeks 40%. DOR 10.5 months. mPFS 2 months. Primary end point threshold not specified.	10.1200/PO.20.00247
GIMR	2025-07-30	FL	3	IL3RA	Overexpression	Acute myeloid leukaemia	IMGN632	Phase 1/2 study. IMGN632. NCT03386513. N=91. Schedule A (n=68), Schedule B (n=23). No maximum tolerated dose defined; 0.045 mg/kg selected as RP2D. ORR 21% (95% CI 8-40; 6/29), composite CR 17% (5/29). Dose-limiting toxicities observed at 0.180, 0.300, 0.450 mg/kg. Phase 1b/2 study initiated with azacitidine and venetoclax in CD123+ AML. Note CD123 expression is not signficantly correlated with response.	38423051
GIMR	2022-05-30	FL	3	Immunoscore IC	High	Colorectal adenocarcinoma	FOLFOXIRI + Bevacizumab + Atezolizumab	NCT03721653. Exploratory analysis from Phase 3 AtezoTRIBE. In experimental group, significant PFS benefit (HR:0.38) was seen in patients with high immunoscore IC treated with atezolizumab plus FOLFOXIRI and bevacizumab. Immunoscore IC digitally measures the densities and proximity of PD-L1 and CD8 cells on a single tissue section.	10.1016/S1470-2045(22)00274-1
GIMR	2023-01-25	FL	3	KIT	Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation	Gastrointestinal stromal tumour	Sunitinib	Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. ORR was 25% in patients with acquired Exon 13/14 mutations following prior imatinib exposure.	38182785, 10.1200/JCO.2023.41.36_suppl.397784
GIMR	2023-01-25	FL	3	KIT	Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation	Gastrointestinal stromal tumour	Ripretinib	Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. ORR 44% (12/27) was observed in patients with acquired Exon 13/14 mutations prior imatinib exposure. Median PFS 14.2 months.	38182785, 10.1200/JCO.2023.41.36_suppl.397784
GIMR	2020-12-31	FL	3	KIT	Exon 11 mutation, Exon 11 deletion, L576P, K642E, I817L, V559A	Melanoma	Nilotinib	Phase 2 UN10-06 trial. Exon 11 mutation ORR 29%. One responder I817L.	26424760
GIMR	2020-04-15	FL	3	KIT	Exon 11 mutation, Exon 13 mutation, V559C, V560D, L576P, D820Y, K642E, N822K	Melanoma	Imatinib	Not TGA approved; Not FDA approved; NCCN 2A; ASCO not recommended. 2 durable CR; 2 durable PR in Phase 2	21642685, 16908931, 23416972
GIMR	2022-08-16	FL	3	KIT	Exon 11 mutation, Exon 9 mutation, Exon 13 mutation, Exon 17 mutation	Gastrointestinal stromal tumour	Ripretinib	Biomarker analysis from phase 3 INVICTUS trial. NCT03353753. Ripretinib showed significant longer PFS and OS over placebo across GIST harbouring KIT mutations in exons 9, 11, 13, 17.	34503977
GIMR	2022-03-20	FL	3	KIT	Exon 9 mutation, Exon 11 mutation, Exon 13 mutation	Gastrointestinal stromal tumour	Imatinib + Binimetinib	Phase 2. NCT01991379. Combination of Imatinib and binimetinib was clinically active and produces deep and durable responses in treatment-naive GIST. Best ORR was 69% (29 of 42 evaluable patient has RECIST confirmed PR). 39 of 41 had Choi PR at 8 weeks. Median PFS was 29.9 months. Median OS was not reached.	35041493
GIMR	2020-05-16	FL	3	KIT	Oncogenic mutations	Gastrointestinal stromal tumour	Pazopanib	Phase 2 PAZOGIST trial. NCT01323400. Pazopanib plus best supportive care improved PFS (HR 0.59) with 4-month PFS 45% versus 18% in best supportive care alone in imatinib and sunitinib-resistant advanced gastrointestinal stromal tumours.	27068858
GIMR	2020-04-15	FL	3	KIT	Oncogenic mutations and NOT Amplification	Melanoma	Imatinib	Phase 2 trial. N=25. Imatinib showed a ORR of 29% in metastatic mucosal, acral, or CSD melanoma with KIT amplifications and/or mutations, with higher response rate in KIT mutated (54%) versus KIT amplified only (0%).	23775962
GIMR	2020-04-15	FL	3	KIT	Oncogenic mutations and NOT Amplification and NOT Exon 17 mutation	Melanoma	Imatinib	Not TGA approved; Not FDA approved; NCCN 2A; ASCO not recommended	21642685, 16908931, 23416972
GIMR	2021-08-18	FL	3	KIT	Oncogenic mutations, V654A, T670I, Exon 17 mutation	Gastrointestinal stromal tumour	Avapritinib	Phase 3. VOYAGER. Avaprintinib vs Regorafenib in biomarker unselected third/fourth-line setting. In non-PDGFRA D842V-mutants, ORR was 16% (38/233). Note Avaprintinib showed no PFS benefit over regorafenib. 	34343033
GIMR	2020-05-07	FL	3	KIT	Oncogenic mutations; Exon 11 mutation; Exon 9 mutation	Gastrointestinal stromal tumour	Nilotinib	Phase 2. N=35. Nilotinib demonstrated a disease control rate of 29% at Week 24, with a median progression-free survival of 113 days, overall survival of 310 days, and an objective response rate of 3% in GIST patients previously resistant to imatinib and sunitinib.	21456006
GIMR	2021-08-13	FL	3	KIT	Protein expression, Oncogenic mutations, Exon 9 mutation, Exon 11 mutation	Gastrointestinal stromal tumour	Cabozantinib	Phase 2. CaboGIST. NCT02216578. N=50. Cabozantinib following failure of imatinib, sunitinib, and regorafenib. At 12 weeks, ORR 14%. DCR 82%. Median PFS 5.5 months.	32470848
GIMR	2026-03-04	FL	3	KMT2A	Rearrangement	Acute myeloid leukaemia	Azacitidine + Venetoclax + Revumenib	Phase 1. NCT03013998. N=43. Azacitidine, venetoclax, and revumenib in newly diagnosed AML aged 60+ with NPM1m or KMT2Ar. ORR 88.4% (NPM1m 85.3%, KMT2Ar 100%). Composite CR 81.4% (NPM1m 79.4%, KMT2Ar 88.9%). CR 67.4% (NPM1m 65%, KMT2Ar 78%). Median time to response 28 days. 100% MRD negative in 37 evaluated patients. High rates of CR and clinical activity observed.	40504618
GIMR	2024-12-06	FL	3	KMT2A	Rearrangement	Acute myeloid leukaemia; Acute lymphoblastic leukaemia	Revumenib	Phase 1. NCT04065399. Revumenib showed low frequency of grade 3 or higher treatment-related adverse events and 30% rate of complete remission or complete remission with partial haematologic recovery in patients with relapsed or refractory acute leukaemia.	36922593
GIMR	2025-05-04	FL	3	KRAS	A146T, G13D	Juvenile myelomonocytic leukaemia	Trametinib	Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months.	38867349
GIMR	2021-09-20	FL	3	KRAS	G12C	Colorectal adenocarcinoma	Adagrasib	KRYSTAL-1: Multicohort phase 1/2. Adagrasib monotherapy: ORR 22% (10/45). DCR 87% (39/45). Median DOR: 4.2 months and median PFS 5.6 months.	10.1016/annonc/annonc741
GIMR	2021-09-20	FL	3	KRAS	G12C	Colorectal adenocarcinoma	Adagrasib + Cetuximab	KRYSTAL-1: Multicohort phase 1/2. Adagrasib and cetuximab combination: ORR 43% (12/28). DCR 100%.	10.1016/annonc/annonc741
GIMR	2025-05-27	FL	3	KRAS	G12C	Colorectal adenocarcinoma	Adagrasib + Cetuximab	Phase 1/2 trial. N=94. Adagrasib + cetuximab in KRASG12C-mutated metastatic colorectal cancer. ORR: 34%. Median PFS: 6.9 months. Median OS: 15.9 months. Grade 3-4 TRAEs in 27.7% patients. No TRAEs led to adagrasib discontinuation.	38587856
GIMR	2023-12-17	FL	3	KRAS	G12C	Colorectal adenocarcinoma	Garsorasib	Phase 1/2 (NCT04585035). N=24. D-1553 demonstrated a activity in heavily pretreated CRC with KRAS G12C mutations. Confirmed ORR was 21%. DCR was 96%.	10.1200/JCO.2023.41.16_suppl.3563
GIMR	2025-05-31	FL	3	KRAS	G12C	Colorectal adenocarcinoma	MK-1084; MK-1084 + Cetuximab	Phase 1 KANDLELIT-001 trial. NCT05067283. MK-1084, a KRAS G12C inhibitor, showed antitumor activity in patients with advanced KRAS G12C-mutated CRC, with ORR of 36% as monotherapy, 50% with cetuximab, and 14% with cetuximab + mFOLFOX6.	10.1200/JCO.2025.43.16_suppl.3508
GIMR	2025-05-31	FL	3	KRAS	G12C	Colorectal adenocarcinoma	Olomorasib + Cetuximab	Phase 1/2 study. NCT04956640. N=93. Olomorasib + cetuximab showed an ORR of 42% and mPFS of 7.5 months in patients with KRAS G12C-mutant CRC, with a favorable safety profile and optimal dose of olomorasib determined as 100 mg BID.	10.1200/JCO.2025.43.16_suppl.3507
GIMR	2025-05-31	FL	3	KRAS	G12C	Colorectal adenocarcinoma	Sotorasib + Panitumumab	Phase 1b CodeBreaK 101 trial. NCT04185883. N=40. Sotorasib + panitumumab + FOLFIRI showed  efficacy in pretreated KRAS G12C-mutated mCRC with ORR of 57.5%, median PFS of 8.2 months, and median OS of 17.9 months.	10.1200/JCO.2025.43.16_suppl.3506
GIMR	2022-02-22	FL	3	KRAS	G12C	Non-small cell lung cancer	Adagrasib	Phase 1/1B. KRYSTAL-1. At 600mg BD, 10/16 evaluable NSCLC with KRAS G12C achieved objective response.	35167329
GIMR	2026-03-04	FL	3	KRAS	G12C	Non-small cell lung cancer	Divarasib	Phase I. GO42144. NCT04449874. N=65. Single-agent divarasib in advanced KRAS G12C-positive NSCLC. Confirmed ORR 55.6% (95% CI, 42.5 to 68.1) in measurable disease (n=63). Median DOR 18.0 months (95% CI, 11.1 to 24.9). Median PFS 13.8 months (95% CI, 9.8 to 25.4) overall and 15.3 months (95% CI, 12.3 to 26.1) at 400-mg dose. 48% treated beyond 1 year.	40632992
GIMR	2023-12-05	FL	3	KRAS	G12C	Non-small cell lung cancer	Garsorasib	Phase 1. NCT04879671. N=79 (combined dose escalation and expansion). In patients with KRAS G12C mutated NSCLC, Treatment with D-1553 (Garsorasib) resulted in ORR of 40% and DCR of 92%. Median PFS was 8 months.	36948246
GIMR	2024-06-09	FL	3	KRAS	G12C	Non-small cell lung cancer	Glecirasib + JAB-3312	Phase 1/2a study, NCT05288205, In front-line NSCLC patients with KRAS G12C mutations (n=102), treated with Glecirasib + JAB-3312, ORR was 65% in all front-line NSCLC patients (77% in the 800mg + 2mg group). Median PFS 12.2 months.	10.1200/JCO.2024.42.16_suppl.3008
GIMR	2023-05-05	FL	3	KRAS	G12C	Non-small cell lung cancer	IBI351	Phase 1. NCT05005234. N=67. NSCLC across all dose levels, the confirmed ORR was 45%, and DCR was 93%.	10.1158/1538-7445.AM2023-CT030
GIMR	2024-06-09	FL	3	KRAS	G12C	Non-small cell lung cancer	Olomorasib	Phase 1/2 LOXO-RAS-20001. N=157. Olomorasib showed activity across KRAS G12C-mutant NSCLC. ORR was 39% with median PFS of 6 months.	10.1200/JCO.2024.42.16_suppl.3007
GIMR	2020-11-03	FL	3	KRAS	G12C	Non-small cell lung cancer; Colorectal adenocarcinoma; Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1 trial. NCT03785249. N=79. Adagrasib demonstrated an ORR of 45% and disease control rate of 96% in patients with advanced/metastatic NSCLC harboring KRAS G12C mutation, with a median time on treatment of 8.2 months.	10.1016/S0959-8049(20)31076-5
GIMR	2023-08-24	FL	3	KRAS	G12C	Non-small cell lung cancer; Colorectal adenocarcinoma; Solid tumours	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. N=137 (NSCLC=60, Colorectal cancer =55, other solid tumors=22). ORR in NSCLC was 53% with PFS: 13.1 months. ORR in CRC was 29% with PFS of 5.6 months. Responses also seen in other solid tumors. 	37611121
GIMR	2025-10-18	FL	3	KRAS	G12C	Non-small cell lung cancer; Colorectal cancer	MK-1084	Phase I KANDLELIT-001 trial. NCT05067283. N=123. ORR 38% (CRC), 38% (NSCLC), 34% (others). Median PFS 6.2 (CRC), 8.3 (NSCLC), 5.7 mo. 	ESMO25.926MO
GIMR	2025-10-19	FL	3	KRAS	G12C	Non-small cell lung cancer; Pancreatic adenocarcinoma; Colorectal adenocarcinoma; Solid tumour	HRS-7058	Phase 1 trial. NCT06383871. N=81. HRS-7058, a KRAS G12C inhibitor, showed promising antitumor activity with ORR of 48% and DCR of 94% in KRAS G12Ci-naive NSCLC. 3/4 patients with PDAC had tumour response.	ESMO25.914O
GIMR	2022-02-15	FL	3	KRAS	G12C	Pancreatic adenocarcinoma	Sotorasib	Combined Phase 1 and 2 CodebreaK 100. NCT03600883. N=38. ORR was 21% (8/38) with DCR of 84% (32/38). Median PFS was 4.0 months with DOR 2.8 months. Median OS 6.9 months.	10.1200/JCO.2022.40.36_suppl.360490
GIMR	2022-12-23	FL	3	KRAS	G12C	Pancreatic adenocarcinoma	Sotorasib	Phase 2. NCT03600883. CodeBreaK 100. N=38. Median prior treatment 2 lines. Objective response 21% (8/38). Median PFS 4.0 months. Median OS 6.9 months. 	36546651
GIMR	2025-10-18	FL	3	KRAS	G12C	Solid tumour except Colorectal adenocarcinoma, Non-small cell lung cancer; Pancreatic adenocarcinoma; Cholangiocarcinoma	Divarasib	Phase 1. GO42144 (NCT04449874) and JO44179 (jRCT2031220195). N=32. Divarasib showed ORR of 34% (11/32) in KRAS G12C-positive non-NSCLC, non-CRC tumors (pancreatic: 27%, median PFS 7.1 mo; cholangiocarcinoma: 25%, median PFS 7.2 mo). Common TRAEs: diarrhea, nausea, anemia; no Grade 4-5 events. Updated TAPISTRY data (N=47) pending. Cholangiocarcinoma 23% (3/13); Pancreatic adenocarcinoma (31%). Other solid tumour (47%)	ESMO25.927MO
GIMR	2023-04-21	FL	3	KRAS	G12C	Solid tumours; Pancreatic adenocarcinoma; Appendiceal carcinoma; Cholangiocarcinoma; Endometrial carcinoma	Adagrasib	Phase 1/2. KRYSTAL-1. N=57. NCT03785249. Adagrasib 600mg BD demonstrated an ORR of 35% (20/57), with 33% in PDAC subgroup and 42% in BTC. DCR was 86%. Median DOR was 5.3 months and median PFS was 7.4 months.	37099736, 10.1200/JCO.2023.41.36_suppl.425082
GIMR	2025-10-19	FL	3	KRAS	G12D	Non-small cell lung cancer; Pancreatic adenocarcinoma; Colorectal adenocarcinoma; Solid tumour	HRS-4642	Phase 1 trial. N=84. HRS-4642, a KRAS G12D inhibitor, showed activity in NSCLC (ORR 24%, mPFS 5.6 months) and PDAC (ORR 21%, mPFS 4.1 months).	ESMO25.915O
GIMR	2024-09-15	FL	3	KRAS	G12D	Solid tumours	ASP3082	Phase 1. NCT05382559. N=98. ASP3082 monotherapy showed response in patients with advanced pancreatic cancer  with ORR 5 of 27 (19%), colorectal cancer, and non-small cell lung cancer 3 of 13 responders. ORR was 33% at 300mg. 	10.1016/j.annonc.2024.08.675
GIMR	2025-06-09	FL	3	KRAS	G12D	Solid tumours; Non-small cell lung cancer; Pancreatic adenocarcinoma	GFH375	Phase 1/2 trial. NCT06500676. N=32. Single-agent GFH375, a KRAS G12D inhibitor that targets both GTP-bound and GDP-bound states of mutant KRASG12D protein, showed anti-tumor activity in patients with advanced solid tumors, with ORR of 27% and DCR of 86% across dose range. ORR 42% in 12 PDAC and 52% in PDAC at target dose range. 	10.1200/JCO.2025.43.16_suppl.3013
GIMR	2025-10-19	FL	3	KRAS	G12D	Solid Tumours; Non-small cell lung cancer; Pancreatic adenocarcinoma; Colorectal adenocarcinoma; Ovarian cancer; Solid tumour	INCB161734	Phase 1. NCT06179160. N=36. INCB161734, a KRAS G12D inhibitor showed promising efficacy in 36 patients with advanced or metastatic solid tumors, with ORR of 30%, and DCR of 85% achieving disease control at doses ≥600 mg qd (PDAC 34%)	ESMO25.916O
GIMR	2026-03-04	FL	3	KRAS	Oncogenic mutations	Colorectal adenocarcinoma	Onvansertib + FOLFIRI + Bevacizumab	Phase II. NCT03829410. N=53. Onvansertib + FOLFIRI + bevacizumab in KRAS-mutant mCRC. ORR 26.4%. Median DOR 11.7 months. No prior bevacizumab subgroup ORR 76.9% vs 10.0% and median PFS 14.9 months vs 6.6 months. First-line evaluation planned (NCT06106308).	39475591, 39561313
GIMR	2020-09-03	FL	3	KRAS	Oncogenic mutations	Low-grade serous ovarian cancer	Binimetinib	MILO/ENGOT-OV11. Negative Ph3 but PFS/ORR signal seen in KRAS oncogenic mutations	32822286
GIMR	2023-05-05	FL	3	KRAS	Oncogenic mutations	Low-grade serous ovarian cancer	Lifirafenib + Mirdametinib	Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. ORR in low-grade serous ovarian cancer was (59%). DCR was 94%.	10.1158/1538-7445.AM2023-CT033
GIMR	2020-07-31	FL	3	KRAS	Oncogenic mutations	Non-small cell lung cancer	Selumetinib + Docetaxel	Ph2 ORR 37%. Negative Ph 3 SELECT-1	23200175, 28492898
GIMR	2025-05-31	FL	3	KRAS	Oncogenic mutations, G12C	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2022-01-03	FL	3	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	Panitumumab + Fluorouracil	Phase 2. PANAMA. N=248. In RAS-wildtype colorectal cancer following first-line induction therapy, maintenance therapy with 5-FU/Leucovorin plus panitumumab was significantly longer than 5-FU/Leucovorin alone (8.8 v 5.7 months, HR, 0.72).	34533973
GIMR	2025-06-23	FL	3	KRAS+TP53	KRAS:Oncogenic mutations and NOT TP53:Alteration	Non-small cell lung cancer	Selinexor + Docetaxel	Phase 1/2 trial. N=40. Selinexor plus docetaxel showed activities in TP53 wild-type KRAS-mutant NSCLC patients with a median PFS of 7.4 months versus 1.8 months in TP53-altered cases, and response rates of 27% versus 9% respectively.	39651955
GIMR	2026-03-04	FL	3	KRSA	G12	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2021-06-18	FL	3	MDM2+TP53	MDM2:Amplification AND NOT TP53:Oncogenic mutations	Dedifferentiated liposarcoma	Brigimadlin	DCR was 28/32. ORR was 12.5%. PFS: 8 months	10.1200/JCO.2021.39.15_suppl.3016, 10.1200/JCO.2022.40.16_suppl.3004
GIMR	2021-06-18	FL	3	MDM2+TP53	MDM2:Amplification AND NOT TP53:Oncogenic mutations	Well-differentiated liposarcoma	Brigimadlin	DCR was 100%. ORR was 27%. with prolonged duration of response	10.1200/JCO.2021.39.15_suppl.3016, 10.1200/JCO.2022.40.16_suppl.3004
GIMR	2023-08-01	FL	3	MDM2+TP53	MDM2:Amplification AND NOT TP53:Oncogenic mutations	Well-differentiated liposarcoma; Dedifferentiated liposarcoma	Brigimadlin	4 of 7 WDLPS achieved partial response with DCR of 100%. 9 of 12 (75%) of DDLPS achieved disease control. 	37269344
GIMR	2021-06-15	FL	3	MET	Alteration, Amplification, Oncogenic mutations	Papillary renal cell carcinoma	Durvalumab + Savolitinib	Phase 2 CALYPSO: MET-driven PRCC. ORR 57% (8/14) 	10.1200/JCO.2021.39.15_suppl.4511
GIMR	2022-01-18	FL	3	MET	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	AMG 337	Phase 2. NCT02016534, Cohort 1. ORR was 18% (8/45). Eligibility criteria was MET/CEN-7 ratio ≥2.0 on FISH.	30366938
GIMR	2022-01-18	FL	3	MET	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Crizotinib	Phase 2. AcSé-Crizotinib. NCT02034981. In chemorefractory patients, the ORR to Crizotinib was 56% (5/9). Response after two cycles were 33%. PFS 3.2 months. MET amplification was determined by copy number >= 6 copies. 	33847874
GIMR	2020-05-06	FL	3	MET	Amplification	Non-small cell lung cancer	Capmatinib	GEOMETRY mono-1: In MET amplified group (defined as gene copy number, GCN, >= 10), ORR 29% (previously treated) versus 40% (previously untreated). Limited response were seen with GCN <10 (ORR 7-12%).	32877583, 10.1200/JCO.2019.37.15_suppl.9004, 10.1200/JCO.2020.38.15_suppl.9509
GIMR	2022-01-12	FL	3	MET	Amplification	Non-small cell lung cancer	Crizotinib	Phase 2. N=38. ORR 38% for high (8/21, >=4 MET-to-CEP7 ratio on FISH), 14% for medium (2/14, >2.2 to <4 MET-to-CEP7 ratio), and 1 in 3 low (≥1.8 to ≤2.2 MET-to-CEP7 ratio). Median PFS were 6.7 months (high), 1.9 months (medium), and 1.8 months (low).	33676017
GIMR	2021-06-28	FL	3	MET	Amplification	Non-small cell lung cancer	Tepotinib	Phase 2 VISION Cohort B. N=24. MET gene copy number >=2.5 by liquid biopsy. No exon 14 skipping mutations. ORR 42%. In previously untreated patient, ORR 71%.	10.1200/JCO.2021.39.15_suppl.9021
GIMR	2026-03-03	FL	3	MET	Amplification	Non-small cell lung cancer	Vebreltinib	Phase 2 KUNPENG trial. NCT04258033. N=86. Vebreltinib showed antitumour activity in patients with MET amplification-driven NSCLC, achieving an ORR of 48.8% (42/86) with a median follow-up of 18.6 months. MET amplification was determined by FISH with a gene copy number (GCN) >= 6 copies. No EGFR mutations, ALK fusion, ROS1 rearrangements, or KRAS mutations. 	41365311
GIMR	2025-10-19	FL	3	MET	Amplification	Solid tumours	Telisotuzumab adizuteca	Phase 1 study. NCT05029882. N=100. Temab-A monotherapy showed activities in patients with MET-amplified advanced solid tumors, with a confirmed ORR of 46% and median PFS of 9.5 months across all dose levels and tumor types, including NSCLC (69%) and GEA (71%).	ESMO25.918O
GIMR	2020-04-27	FL	3	MET	Amplification, D1010 (D1028), Exon 14 Deletion, Exon 14 splicing mutation, Y1003 (Y1021)	Non-small cell lung cancer	Crizotinib	Not TGA or FDA approved; NCCN Category 2A. Note: no conclusive data from large trials to date.	26729443, 10.1200/jco.2014.32.15_suppl.8001
GIMR	2025-05-31	FL	3	MET	Exon 14 deletion, Exon 14 splicing mutation, 	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed  activity in NSCLC patients with driver mutations outside of classic KRAS/MET alterations, with ORR of 40% and mPFS of 7.0 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2020-05-15	FL	3	MET	Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	Crizotinib	Phase 2/retrospective study. Crizotinib showed antitumor activity in 69 patients with NSCLC harboring MET exon 14 alterations with an ORR of 32%, median DOR of 9.1 months, and median PFS of 7.3 months.	31932802
GIMR	2022-01-12	FL	3	MET	Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	Crizotinib	Phase 2. NCT02499614. N=26. In previously treated NSCLC patients, the ORR was 27% (7/26). PFS 4.4 months. OS 5.4 months. MET amplification defined as MET/CEP7 ratio > 2.2.	31416808
GIMR	2020-05-20	FL	3	MET	Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	Savolitinib	Phase 2 study. NCT02897479. Savolitinib showed an IRC-assessed ORR of 49% (30/61) in patients with MET exon 14 skipping pulmonary sarcomatoid carcinoma and other NSCLC subtypes.	34166627, 10.1200/JCO.2020.38.15_suppl.9519
GIMR	2025-07-04	FL	3	MET	Exon 14 skipping mutation, Exon 16 mutation, H1094Y, c.3028+1G>T, c.3028+1G>A, c.3028G>A, c.3028+1G>C, C.2888-27_2888-2delinsC, c.2935_2939del, c.2888-14_2888-4del, c.2888-17_2888-6del c.2888-18_2888-9del, c.2888-20_2888-11del, c.3028+1G>C, c.3028G>C, c.3028G>T, c.3028G>C, c.3028+2T>C, C.3028+2T>A, C.3028+2T>A, c.3028+3A>G, c.3280C>T	Non-small cell lung cancer	Crizotinib	Phase 2. Drug Rediscovery Protocol. NCT0295234. N=30. Crizotinib achieved clinical benefit in 70.8% of MET-mutated non-small cell lung cancer patients (CB: 70.8% [95% CI, 48.9-87.4]), with ORR 62.5% (95% CI, 40.6-81.2). Median PFS 10.2 months (95% CI, 6.0-20.1), OS 13.0 months (95% CI, 9.0-not available). One CR patient harbored a tyrosine kinase domain mutation (p.H1094Y); others had MET exon 14 skipping mutations.	39352721
GIMR	2020-05-30	FL	3	MET	Oncogenic mutations, Amplification	Papillary renal cell carcinoma	Savolitinib	Phase 3 SAVOIR trial. NCT03091192. N=60. Savolitinib showed numerically greater PFS (7.0 months vs 5.6 months), OS, and ORR compared to sunitinib in patients with MET-driven papillary renal cell carcinoma, with fewer grade 3 or higher AEs (42% vs 81%). Statistical significance for the primary endpoint was not demonstrated in the phase 3 SAVOIR trial due to poor recruitment.	32469384, 10.1200/JCO.2020.38.15_suppl.5002
GIMR	2021-06-10	FL	3	MET	Overexpression	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 1 CHRYSALIS. ORR 90% (9 in 10) in patients with IHC positive (defined as combined EGFR+MET H score >= 400)	10.1200/JCO.2021.39.15_suppl.9006
GIMR	2025-06-04	FL	3	MET	Overexpression, Amplification, Oncogenic mutation	Solid tumours	SHR-1826	Phase 1 study. NCT06094556. N=116. SHR-1826, a c-MET-directed antibody-drug-conjugate, demonstrated a manageable safety profile and  anti-cancer activity in heavily pretreated advanced solid tumors, particularly in NSCLC patients with an ORR of 40% and median PFS of 6.8 months.	10.1200/JCO.2025.43.16_suppl.106
GIMR	2024-06-02	FL	3	MET	PTPRZ1-MET fusion	Glioblastoma	Vebreltinib	Phase 2/3. FUGEN, NCT06105619. Vebreltinib improved OS (6.3 vs 3.4 months) and PFS (1.9 vs 1.1 months) over chemotherapy in previously treated, PTPRZ1-MET fusion positive secondary glioblastoma, IDH-mutant glioblastoma patients.	10.1200/JCO.2024.42.16_suppl.2003
GIMR	2022-03-23	FL	3	MGMT	Loss of protein expression, Promoter methylation	Colorectal adenocarcinoma	Temozolomide + Ipilimumab + Nivolumab	Phase 2 trial. MAYA. NCT03832621. In pre-treated, MGMT-silenced MSS colorectal cancer, sequencing temozolomide by priming followed by immune checkpoint blockade may induce durable clinical benefit. PFS at 8 months was 36%. Median PFS was 7.0 months. Medial OS was 18.4 months.	35258987
POTTR	2020-04-16	ST	3	MGMT	Promoter methylation	Glioblastoma	Temozolomide	Standard of care. NCCN Category 1. MGMT promoter methylation in glioblastoma (45% of 206 cases) correlates with improved survival (HR, 0.45) and significant survival benefit when combined with temozolomide and radiotherapy (21.7 months vs 15.3 months), serving as an essential diagnostic, prognostic, and predictive biomarker without necessarily changing treatment recommendations.	15758010
GIMR	2025-01-12	FL	3	Microsatellite Instability	High	Prostate cancer	Ipilimumab + Nivolumab	Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months. 	39293514
GIMR	2022-05-30	FL	3	Mismatch repair	Deficient	Colorectal adenocarcinoma	FOLFOXIRI + Bevacizumab + Atezolizumab	NCT03721653. Exploratory analysis from Phase 3 AtezoTRIBE. In experimental group, significant PFS benefit (HR:0.19) was seen in patients with mismatch repair reficiency treated with atezolizumab plus FOLFOXIRI and bevacizumab.	10.1016/S1470-2045(22)00274-1
GIMR	2023-07-14	FL	3	Mismatch repair	Deficient	Endometrial cancer	Durvalumab	PHAEDRA. Phase 2. ORR in the dMMR cohort was 47% (17 of 36) with median PFS of 8.3 months.	34103352
GIMR	2025-01-12	FL	3	Mismatch repair	Deficient	Prostate cancer	Ipilimumab + Nivolumab	Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. Highest response was seen in dMMR/MSI subgroup (81%). Median PFS was 4.0 months. 	39293514
GIMR	2021-04-23	FL	3	Mismatch repair	Deficient	Solid tumours	Dostarlimab	GARNET: ORR 39% in dMMR patients across tumour types. Note: no responses seen in 4 pancreatic cancer cases.	10.1200/JCO.2021.39.3_suppl.9
GIMR	2020-04-27	FL	3	Mismatch repair	Deficient	Solid tumours except Colorectal adenocarcinoma	Nivolumab	NCI-MATCH (EAY131) Z1D-A subprotocol. Defined as complete loss of MLH1/MSH2 IHC. ORR 36%	31765263
GIMR	2020-04-27	FL	3	MLH1	Loss of protein expression	Solid tumours except Colorectal adenocarcinoma	Nivolumab	NCI-MATCH (EAY131) Z1D-A subprotocol. Defined as complete loss of MLH1/MSH2 IHC. ORR 36%	31765263
GIMR	2020-04-27	FL	3	MSH2	Loss of protein expression	Solid tumours except Colorectal adenocarcinoma	Nivolumab	NCI-MATCH (EAY131) Z1D-A subprotocol. Defined as complete loss of MLH1/MSH2 IHC. ORR 36%	31765263
GIMR	2024-10-04	FL	3	MTAP	Deletion, Loss of protein expression	Solid tumours	AMG 193	Phase 1. NCT05094336. In patients with MTAP-deleted solid tumors, the MTA-cooperative PRMT5 inhibitor AMG 193 showed ORR of 21% across dose ranges of 800 mg o.d., 1200 mg o.d., or 600 mg b.i.d.. Responses were seen in cholangiocarcinoma, oesophageal carcinoma, gallbladder adenocarcinoma, melanoma, non-small cell lung carcinoma, pancreatic adenocarcinoma, renal cell carcinoma, Sertoli-Leydig cell tumor	39293516
GIMR	2025-10-19	FL	3	MUC1	Protein expression	Solid tumours	DS-3939	Phase 1/2 FIH study NCT05875168. N=47. DS-3939, a tumour associated-MUC1-directed ADC, showed early signal of clinical activity in pretreated patients with various solid tumors, with 10 confirmed partial responses observed across NSCLC, OC, and BC.	ESMO25.917O
GIMR	2020-06-30	FL	3	MYD88	Gain-of-function mutations, L265P, S243N, M232T	Diffuse large B-cell lymphoma; Waldenstroms macroglobulinaemia	Ibrutinib	Case series. MYD88 mutation analysis in Waldenstorm's macroglobulinemia patients showed that MYD88 mutations (L265P, S243N, and M232T) were associated with response to ibrutinib therapy, with no major responses observed in patients with wild-type MYD88.	26244327
GIMR	2024-06-09	FL	3	NECTIN4	Protein expression	Solid Tumours; Urothelial carcinoma; Cervical Cancer; Oesophageal cancer; Triple-negative breast cancer	9MW2821	Phase 1/2a, NCT05216965, n=260, 9MW2821, a nectin-4 antibody-drug conjugate, showed ORR of 35% and DCR of 78% at 1.25 mg/kg or above. Median PFS ranging from 3.7 to 8.8 months across different tumor types. Objective response rates were 62, 38, 30, and 44% for urothelial, cervical, oesophageal, and triple negative breast cancers respectively.	40288679, 10.1200/JCO.2024.42.16_suppl.3013
GIMR	2021-06-12	FL	3	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis	FCN-159	Phase 1/2. NCT04954001. N=65. In pediatric patients with neurofibromatosis type 1-related plexiform neurofibromas. ORR was 42% in 19 patients with evaluable response. Median DOR could not be evaluated.	10.1200/JCO.2023.41.16_suppl.10023
GIMR	2021-02-02	FL	3	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis	Mirdametinib	NF106. Phase 2 trial. N=19. NCT02096471. ORR 42%; CBR 95% with significant durable decreases in pain ratings in patients with NF1-related plexiform neurofibromas.	33507822
GIMR	2020-04-16	FL	3	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis 	Cabozantinib	Phase 2 trial. NCT02101736. N=19. Cabozantinib showed partial response in 42% of patients with neurofibromatosis type 1-related plexiform neurofibromas, with median change in tumor volume of 15.2%.	33442015
GIMR	2024-06-02	FL	3	NF2	Oncogenic mutations	Meningioma	Abemaciclib	Phase 2 Alliance A071401 trial. N=36. Abemaciclib improved PFS at 6 months of 54% in patients with recurrent or progressive grade 2/3 meningiomas and NF2 mutations or CDK pathway alterations, meeting primary endpoint. No objective responses observed.	10.1200/JCO.2024.42.16_suppl.2001
GIMR	2020-05-30	FL	3	NF2	Oncogenic mutations	Meningioma	GSK2256098	Phase 2 Alliance A071401 trial. NCT02523014. N=36. GSK2256098 showed activity in NF2-mutated meningiomas, meeting PFS6 endpoint with rates of 83% (grade 1) and 33% (grade 2/3), and one partial response was observed. Updated 2024-09-24.	36288512, 10.1200/JCO.2020.38.15_suppl.2502
GIMR	2021-11-04	FL	3	NOTCH1	R2327fs*	Adenoid cystic carcinoma	Nirogacestat	Case report. Response of tracheal adenoid cystic carcinoma to the gamma secretase inhibitor with TTP of 6.5 months.	34994644
GIMR	2026-03-04	FL	3	NPM1	Oncogenic mutation	Acute myeloid leukaemia	Azacitidine + Venetoclax + Revumenib	Phase 1. NCT03013998. N=43. Azacitidine, venetoclax, and revumenib in newly diagnosed AML aged 60+ with NPM1m or KMT2Ar. ORR 88.4% (NPM1m 85.3%, KMT2Ar 100%). Composite CR 81.4% (NPM1m 79.4%, KMT2Ar 88.9%). CR 67.4% (NPM1m 65%, KMT2Ar 78%). Median time to response 28 days. 100% MRD negative in 37 evaluated patients. High rates of CR and clinical activity observed.	40504618
GIMR	2026-03-04	FL	3	NPM1	Oncogenic mutation	Acute myeloid leukaemia	Ziftomenib	Phase II. KOMET-001. NCT04067336. N=92. Ziftomenib met primary endpoint CR/CRh rate 22% (95% CI, 14 to 32) in relapsed/refractory NPM1-mutated AML. ORR 33% (95% CI, 23 to 43). Median DOR 4.6 months (95% CI, 2.8 to 7.4). Median OS 6.6 months (95% CI, 3.6 to 8.6). 61% negative for measurable residual disease. Comparable CR/CRh regardless of prior venetoclax or comutations.	40997296
GIMR	2020-04-16	FL	3	NRAS	Oncogenic mutations	Histiocytosis	Cobimetinib	Phase 2 proof-of-concept umbrella trial. N=18. Cobimetinib showed an ORR of 89% with durable responses and 94% of patients remaining progression-free at 12 months in patients with histiocytic neoplasms harbouring various MAPK pathway mutations.	30867592
GIMR	2020-10-13	FL	3	NRAS	Oncogenic mutations	Melanoma	Binimetinib	Not TGA approved. Positive Phase 3 NEMO result, but  overall small absolute PFS gain. FDA application withdrawn and NCCN 2B. Revised Tier 3	28284557
GIMR	2023-03-30	FL	3	NRAS	Oncogenic mutations	Melanoma	Naporafenib + Trametinib	Phase 1B. NCT02974725. ORR for the Naporafenib 200mg BD and Trametinib 1mg QD group group was 7/15 (47%) and 2/15 (13%) for the Naporafenib 400mg BD and Trametinib 0.5mg QD group. Overall DCR was 73% in 30 patients.	36947734
GIMR	2020-06-11	FL	3	NRAS	Oncogenic mutations	Melanoma	Ribociclib + Binimetinib	Phase 1b/2 trial. NCT01781572. N=41 (phase II cohort). Ribociclib + binimetinib showed an ORR of 20% (8/41) and 33% (13/40) in patients with concurrent alterations of CDKN2A, CDK4, or CCND1. Median PFS was 3.7 months and median OS was 11.3 months.	35294522, 10.1200/JCO.2017.35.15_suppl.9519
GIMR	2025-04-24	FL	3	NRAS	Oncogenic mutations	Melanoma	Trametinib	Retrospective study. N=33. MEK inhibitors showed 18.2% ORR and 48.5% DCR in pre-treated NRAS-mutated metastatic melanoma patients, with median PFS of 2.8 months and OS of 7.1 months. [Updated from 2020-06-11]	35272084
GIMR	2026-03-04	FL	3	NRAS	Q61L	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2025-05-04	FL	3	NRAS	Q61L, G12S	Juvenile myelomonocytic leukaemia	Trametinib	Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months.	38867349
GIMR	2021-06-05	FL	3	NRAS	Q61R, Q61K	Melanoma	Belvarafenib + Cobimetinib	Phase 1 Dose expansion. ORR: 5/13 (38%) including patients with prior exposure. Median PFS 7.3 mo. However, no responses seen in G12S. 	10.1200/JCO.2021.39.15_suppl.3007
GIMR	2021-06-12	FL	3	NRG1	Fusions, ATP1B1-NRG1 fusion, CD74-NRG1 fusion, ITGB1-NRG1 fusion, SDC4-NRG1 fusion, SLC3A2-NRG1 fusion, ITGB1-NRG1 fusion	Solid tumours; Non-small cell lung cancer	Seribantumab	Phase 2. Cohort 1. In 12 of 15 patients (14 NSCLC patients, 1 pancreatic cancer) with evaluable disease, ORR  was 33% (4/12, including 2 CR), and DCR was 92% (11/12).	10.1200/JCO.2022.40.16_suppl.3006
GIMR	2021-06-05	FL	3	NRG1	Fusions, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, CD74-NRG1 fusion	Solid tumours	Zenocutuzumab	Phase 1/2 trial. N=51. Solid tumours including pancreatic adenocarcinoma, non-small cell lung cancer. ORR entire cohort 29%. ORR pancreatic cancer: 5/12 (42%) with durable analysis 100% CA19-9 reduction. ORR NSCLC 6/24 (25%).	10.1200/JCO.2021.39.15_suppl.3003
GIMR	2022-06-04	FL	3	NTRK1	Fusions	Solid tumours	Entrectinib	STARTRK-2. NCT02568267. N=150 with ORR of 61% (92/150).	10.1200/JCO.2022.40.16_suppl.3099
GIMR	2022-06-04	FL	3	NTRK1	Fusions	Solid tumours	Larotrectinib	Pooled data from NCT02576431, NCT02122913, NCT02637687. N=269 with ORR of 69%	10.1200/JCO.2022.40.16_suppl.3100
GIMR	2025-06-23	FL	3	NTRK1	Fusions, TPM3-NTRK2 fusion, TPR-NTRK2 fusion, IRF2BP2-NTRK2 fusion, KIF21B-NTRK2 fusion, LMNA-NTRK2 fusion, MEF2D-NTRK2 fusion, ARHGEF2-NTRK2 fusion, PDP0E4IP-NTRK2 fusion, CGN-NTRK2 fusion, KIRREL-NTRK2 fusion	High-grade gliomas; Low-grade gliomas; Central nervous system cancer	Larotrectinib; Entrectinib; Repotrectinib; Selitrectinib	Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment.	39625867
GIMR	2025-08-21	FL	3	NTRK1	TMP3-NTRK1 fusion, DCTN1-NTRK1 fusion, LMNA-NTRK1 fusion, BCAN-NTRK1 fusion, TPR-NTRK1 fusion	Infantile Fibrosarcoma; Solid Tumors	Larotrectinib	Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy.	39652801
GIMR	2025-08-21	FL	3	NTRK2	AFAP1-NTRK2 fusion	Solid tumours	Larotrectinib	Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy.	39652801
GIMR	2022-06-04	FL	3	NTRK2	Fusions	Solid tumours	Entrectinib	STARTRK-2. NCT02568267. N=150 with ORR of 61% (92/150).	10.1200/JCO.2022.40.16_suppl.3099
GIMR	2022-06-04	FL	3	NTRK2	Fusions	Solid tumours	Larotrectinib	Pooled data from NCT02576431, NCT02122913, NCT02637687. N=269 with ORR of 69%	10.1200/JCO.2022.40.16_suppl.3100
GIMR	2025-06-23	FL	3	NTRK2	Fusions, AGAP1-NTRK2 fusion, BEND5-NTRK2 fusion, STRN-NTRK2 fusion, KCTD8-NTRK2 fusion, KANK2-NTRK2 fusion, QKI-NTRK2 fusion, NACC2-NTRK2 fusion, KANK1-NTRK2 fusion, SPEC1L-NTRK2 fusion, GKAP1-NTRK2 fusion, KCTD16-NTRK2 fusion, CHAMP1-NTRK2 fusion, CCDC88A-NTRK2 fusion, DNM3-NTRK2 fusion, SBF2-NTRK2 fusion, UGDH-NTRK2 fusion, STMN1-NTRK2 fusion, ATP6V1A-NTRK2 fusion, VAMP4-NTRK2 fusion, SHANK1-NTRK2 fusion, SORBS1-NTRK2 fusion, ABI2-NTRK2 fusion, GNAI1-NTRK2 fusion, SOS1-NTRK2 fusion, DENND5A-NTRK2 fusion, C1orf112-NTRK2 fusion, TLE1-NTRK2 fusion, PHF20L1-NTRK2 fusion, CYP2E1-NTRK2 fusion, PAPPA-NTRK2 fusion	High-grade gliomas; Low-grade gliomas; Central nervous system cancer	Larotrectinib; Entrectinib; Repotrectinib; Selitrectinib	Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment.	39625867
GIMR	2025-08-21	FL	3	NTRK3	ETV6-NTRK3 fusion, VIM-NTRK3 fusion, EML4-NTRK3 fusion, RBPMS-NTRK3 fusion	Infantile Fibrosarcoma; Solid Tumors	Larotrectinib	Phase 3. ADVL1823. N=33. ORR within six cycles was 94% in infantile fibrosarcoma (17/18) and 60% in other NTRK fusion-positive solid tumors (9/15). Two-year EFS and OS were 82.2% and 93.8% for IFS, and 80% and 93.3% for other tumors, respectively; surgical resection correlated with prolonged EFS (only 1/16 progressed), and 6% (2/33) developed progressive disease on therapy.	39652801
GIMR	2022-06-04	FL	3	NTRK3	Fusions	Solid tumours	Entrectinib	STARTRK-2. NCT02568267. N=150 with ORR of 61% (92/150).	10.1200/JCO.2022.40.16_suppl.3099
GIMR	2022-06-04	FL	3	NTRK3	Fusions	Solid tumours	Larotrectinib	Pooled data from NCT02576431, NCT02122913, NCT02637687. N=269 with ORR of 69%	10.1200/JCO.2022.40.16_suppl.3100
GIMR	2025-06-23	FL	3	NTRK3	Fusions, ETV6-NTRK3 fusion, EML4-NTRK3 fusion, BCR-NTRK3 fusion, KANK1-NTRK3 fusion, FOXJ2-NTRK3 fusion, MYO5A-NTRK3 fusion, MN1-NTRK3 fusion, EGR3-NTRK3 fusion, SPEC1L-NTRK3 fusion, SOX6-NTRK3 fusion	High-grade gliomas; Low-grade gliomas; Central nervous system cancer	Larotrectinib; Entrectinib; Repotrectinib; Selitrectinib	Retrospective cohort study. N=119. Patients with TRK fusion-driven CNS tumors. Pediatric patients (median age 4.5 years) with LGG had a better outcome compared to adults and HGG. TRK inhibitors (Larotrectinib) improved tumor control with 68.8% objective response compared to 38.1% with nontargeted treatment.	39625867
GIMR	2020-05-30	FL	3	PALB2	Oncogenic mutations (germline)	Breast cancer	Olaparib	Phase 2 TBCRC-048. N=54. Olaparib showed ORR of 75% in gPALB2-mutated MBC (Cohort 1a) and 36.7% in sBRCA-mutated MBC (Cohort 2a), with median PFS of 9.6 months and 5.6 months, respectively	33119476, 10.1200/JCO.2020.38.15_suppl.1002, 10.1200/JCO.2024.42.16_suppl.1021
GIMR	2023-11-27	FL	3	PALB2	Oncogenic mutations (germline)	Breast cancer	Talazoparib	Phase 2. NCT02401347. PFS was 6.5 months (95% CI, 2.8-10.2) in patients with pretreated advanced HER2-negative breast cancer and other solid tumors with mutations in homologous recombination pathway genes other than BRCA1/2. In patients with breast cancer, overall response rate was 31% (4 partial responses), and clinical benefit rate was 54%. All patients with germline mutations in PALB2 had treatment-associated tumor regression.	36253484
GIMR	2020-04-25	FL	3	PALB2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Cisplatin + Gemcitabine	Phase 2 trial. N=50. Cisplatin and gemcitabine in germline BRCA1/2 or PALB2 mutant PDAC demonstrated ORR 65%, DCR 78%, median PFS 9.7 months, and median OS 16.4 months.	31976786
GIMR	2021-05-12	FL	3	PALB2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Rucaparib	Phase 2 trial of maintenance Rucaparib (after first-line chemotherapy) in platinum-sensitive advanced pancreatic cancer. PFS6 60% with median 13.1 months. ORR 42% in 36 patients. 	33970687
GIMR	2025-07-30	FL	3	PIK3CA	C420R, E542K, E545A, E545D, E545G, E545K, Q546E, Q546R, H1047L, H1047R, H1047Y	Breast cancer	Alpelisib + Fulvestrant	Phase 2. BYLieve. NCT03056755. N=127 (Cohort A). Alpelisib + fulvestrant met primary endpoint of 6-month PFS (53.8%, 95% CI 44.4–63.0) in PIK3CA-mutated, hormone receptor-positive, HER2-negative advanced breast cancer post CDK4/6 inhibitor. Median PFS 8.0 months, OS 27.3 months. Adverse events included hyperglycaemia (29%) and rash (10%). Original curation: 2021-04-07. Updated 2025-07-30	33794206, 39637900
GIMR	2022-06-15	FL	3	PIK3CA	E542K, E545K, H1047L, H1047R	Breast cancer	Capivasertib + Fulvestrant	Phase 2. FAKTION. Biomarker analysis. In expanded pathway altered group (PIK3CA hotspot, AKT1 E17K, and PTEN altered), PFS was significantly prolonged when capiversertib was added to fulvestrant (12.8 months vs placebo, 4.6 months).  OS: 38.9 vs 20.0 months.	35671774, 10.1200/JCO.2022.40.16_suppl.1005
GIMR	2024-09-15	FL	3	PIK3CA	H1047R, H1047L, M1043, E545K, G1049R, Kinase domain mutation, Helical domain mutation	Solid tumours	STX-478	Phase 1/2 trial. NCT05768139. N=61. In advanced solid tumor patients STX-478, monotherapy showed an ORR of 21% in 43 evaluable patients. DCR was 70%.	10.1016/j.annonc.2024.08.2266
GIMR	2020-11-15	FL	3	PIK3CA	Oncogenic mutations	Breast cancer	Buparlisib + Fulvestrant	PFS 4.7 v 1.4 mo HR 0.39. Retrospective biomarker analysis	29508760
GIMR	2020-05-31	FL	3	PIK3CA	Oncogenic mutations, C420R, E453K, E542, E545, Q546, E726, H1047	Solid tumours	Copanlisib	Phase 2. NCI-MATCH Z71F. N=25 in the primary efficacy analysis. ORR was 16% (4/25) versus 5% (null hypothesis). Median PFS 3.4 months. Median OS 5.9 months. CBR was 36%. No objective response was observed in the GI cancers.	35133871, 10.1200/JCO.2020.38.15_suppl.3506
GIMR	2020-12-11	FL	3	PIK3CA	R88Q, N345K, C420R, E542, E545, Q546, M1043I, H1047, G1049R	Triple-negative breast cancer	Capivasertib + Paclitaxel	PAKT PFS 9.3 v 3.7 mo in PIK3CA/AKT/PTEN altered subgroup. OS/ORR NS	31841354
GIMR	2020-05-15	FL	3	PIK3CA	R88Q, N345K, C420R, E542, E545, Q546, M1043I, H1047, G1049R	Triple-negative breast cancer	Ipatasertib + Paclitaxel	LOTUS trial – Ipatasertib + Taxol in TNBC	28800861
GIMR	2020-04-26	FL	3	PIK3CA+ESR1+ERBB2	PIK3CA:Oncogenic mutations and ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	Buparlisib + Fulvestrant	BELLE-2 and BELLE-3. Exploratory subgroup	28576675, 29223745
GIMR	2022-06-15	FL	3	PIK3CA+FGFR1	PIK3CA:Oncogenic mutation AND FGFR1:Alteration	Breast cancer	Fulvestrant + Alpelisib	Biomarker analysis of SOLAR-1. In PIK3CA and FGFR altered cohort, significant longer PFS was seen in alpelisib 12.7 months vs placebo 3.8 months. 	10.1200/JCO.2022.40.16_suppl.1006
GIMR	2022-06-15	FL	3	PIK3CA+FGFR2	PIK3CA:Oncogenic mutation AND FGFR2:Alteration	Breast cancer	Fulvestrant + Alpelisib	Biomarker analysis of SOLAR-1. In PIK3CA and FGFR altered cohort, significant longer PFS was seen in alpelisib 11.0 months vs placebo 9.6 months. 	10.1200/JCO.2022.40.16_suppl.1006
GIMR	2025-01-19	FL	3	POLD1	D402N, L606M	Colorectal cancer	Durvalumab; Ipilimumab + Nivolumab; Nivolumab; Pembrolizumab	Retrospective study. N=27. POLE/POLD1 proofreading-deficient metastatic CRC patients treated with immune checkpoint inhibitors showed ORR of 89%. Entry has been curated and tierd based on evidence of activity as demonstrated by the ORR, prolonged PFS, despite the absence of a prospective trial.	38777726
GIMR	2025-01-19	FL	3	POLE	P286R, S297Y, S297F, F367S, V411L, L424I, P436R, S459F, A456P	Colorectal cancer	Durvalumab; Ipilimumab + Nivolumab; Nivolumab; Pembrolizumab	Retrospective study. N=27. POLE/POLD1 proofreading-deficient metastatic CRC patients treated with immune checkpoint inhibitors showed ORR of 89%. Entry has been curated and tierd based on evidence of activity as demonstrated by the ORR, prolonged PFS, despite the absence of a prospective trial.	38777726
GIMR	2021-07-02	FL	3	POLE	P286R, V411L	Solid tumours	Nivolumab	Phase 2. AcSé. NCT03012581. N=15 (10 evaluable). Mismatch proficient tumours with POLE exonuclease domain mutations. Responders were seen in three patients with P286R and V411L mutations and in colorectal and cervical cancers. No response in non-pathogenic mutations.	10.1016/j.annonc.2020.08.640
GIMR	2020-04-16	FL	3	PSMA	Protein expression	Prostate cancer	Lu-177 vipivotide tetraxetan	Phase 2. PSARR: 66% v Cabazitaxel	10.1200/JCO.2020.38.15_suppl.5500, 29752180
GIMR	2020-04-16	FL	3	PTCH1	Truncating mutations	Basal cell carcinoma	Vismodegib	STEVIE trial. The drug is TGA-approved but not selected by PTCH1 mutation.	19726763, 22670904, 22670903, 29073584
GIMR	2022-06-15	FL	3	PTEN	Alteration	Breast cancer	Capivasertib + Fulvestrant	Phase 2. FAKTION. Biomarker analysis. In expanded pathway altered group (PIK3CA hotspot, AKT1 E17K, and PTEN altered), PFS was significantly prolonged when capiversertib was added to fulvestrant (12.8 months vs placebo, 4.6 months).  OS: 38.9 vs 20.0 months.	35671774, 10.1200/JCO.2022.40.16_suppl.1005
GIMR	2020-12-11	FL	3	PTEN	Loss-of-function mutations	Triple-negative breast cancer	Capivasertib + Paclitaxel	Randomised phase 2 PAKT trial. N=140. Median PFS was 5.9 months with capivasertib plus paclitaxel versus 4.2 months with placebo (HR, 0.74). In patients with PIK3CA/AKT1/PTEN-altered tumors (n = 28), median PFS was 9.3 months versus 3.7 months (HR, 0.30). Median OS was 19.1 months versus 12.6 months (HR, 0.61, NS).	31841354
GIMR	2021-07-09	FL	3	PTEN	Loss-of-function mutations, loss of protein expression	Gastric cancer	GSK2636771	Phase 1b/2 trial. NCT02615730. In patients with PTEN-deficient advanced gastric cancer, GSK2636771 combined with paclitaxel achieved median PFS of 12.1 weeks and OS of 33.4 weeks. Patients with PTEN-null tumors exhibited superior PFS compared to those with PTEN partial loss tumors.	10.1016/j.annonc.2021.05.034
GIMR	2020-05-15	FL	3	PTEN	Oncogenic mutations	Triple-negative breast cancer	Ipatasertib + Paclitaxel	LOTUS trial – Ipatasertib + Taxol in TNBC	28800861
GIMR	2020-06-21	FL	3	PTEN+ERBB2	PTEN:Loss of protein expression and ERBB2:amplification	Breast cancer	Everolimus + Trastuzumab	BOLERO-3 subgroup	24742739
GIMR	2025-05-04	FL	3	PTPN11	E76V, D61V	Juvenile myelomonocytic leukaemia	Trametinib	Phase 2. NCT03190915. N=10. Trametinib showed an ORR of 50% in relapsed/refractory Juvenile myelomonocytic leukaemia, with 7 patients completing maximum 12 cycles or proceeding to HSCT and alive at median follow-up of 24 months.	38867349
GIMR	2020-04-16	FL	3	RAF1	Oncogenic mutations, K106N	Histiocytosis	Cobimetinib	Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations.	30867592
GIMR	2026-03-04	FL	3	RET	Fusion	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2021-06-05	FL	3	RET	Fusions	Medullary thyroid cancer	BOS172738	Phase 1 study. NCT03780517. BOS172738, a potent and selective RET inhibitor, showed an ORR of 33% in RET-altered tumors, including 33% in NSCLC and 44% in MTC (7/16, including 1 CR), with a favorable safety profile and durable responses.	10.1200/JCO.2021.39.15_suppl.3008
GIMR	2021-06-05	FL	3	RET	Fusions	Non-small cell lung cancer	BOS172738	ORR 33% (10/30)	10.1200/JCO.2021.39.15_suppl.3008
GIMR	2020-11-17	FL	3	RET	Fusions	Non-small cell lung cancer	Lenvatinib	Phase 2 trial. NCT01877083. N=25. Lenvatinib demonstrated an ORR of 16% and a median PFS of 7.3 months in patients with RET fusion-positive lung adenocarcinoma.	31710864
GIMR	2020-04-27	FL	3	RET	Fusions	Non-small cell lung cancer	Vandetanib	Phase 2 trial. N=18. Vandetanib showed an ORR of 18% and DCR of 65% in pretreated NSCLC patients with RET rearrangement, with a median PFS of 4.5 months and OS of 11.6 months.	27803005
GIMR	2020-11-17	FL	3	RET	Fusions	Non-small cell lung cancer	Vandetanib	Phase 2 LURET trial. UMIN000010095. Vandetanib showed an ORR of 53% (9/17) and median PFS of 4.7 months in patients with RET-rearranged advanced NSCLC, indicating RET rearrangement as a targetable alteration.	27825616
GIMR	2020-11-17	FL	3	RET	Fusions	Non-small cell lung cancer	Vandetanib	Single-arm phase 2. ORR 18%. PFS 4.5mo	27803005
GIMR	2023-07-13	FL	3	RET	Fusions	Non-small cell lung cancer; Solid tumours	KL590586	Phase 1. NCT05265091. ORR in solid tumour was 60%, 70% and 81% in pretreated and treatment-naive NSCLC respectively.	JCO.2023.41.16_suppl.3007
GIMR	2020-05-31	FL	3	RET	Fusions	Solid tumours	Pralsetinib	Phase 1/2 ARROW study. NCT03037385. Pralsetinib demonstrated an ORR of 75% in thyroid cancer and 60% in of solid tumours harbouring RET fusions, with durable responses across multiple fusion genotypes.	10.1200/JCO.2020.38.15_suppl.109
GIMR	2020-04-27	FL	3	RET	Fusions, KIF5B-RET fusion, Rearrangement	Non-small cell lung cancer	Cabozantinib	Phase 2 trial. NCT01639508. N=26. Cabozantinib yielded an ORR of 28% in patients with RET-rearranged non-small-cell lung cancer, with KIF5B-RET being the predominant fusion type.	27825636
GIMR	2023-11-20	FL	3	RET	Fusions, Oncogenic mutations	Solid tumour	KL590586	Phase 1 KL400-I/II-01 trial. NCT05265091. In the dose expansion part (n=69), ORR was 64% in RET altered tumors including NSCLC, MTC, pancreatic cancer and ovarian cancer. ORR in systemic pretreated NSCLC was 63%, DCR 91%. ORR in treatment nave NSCLC was 76% with DCR of 92%. CNS DCR was 100%.	10.1200/JCO.2023.41.16_suppl.3007
GIMR	2026-03-04	FL	3	RET	KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, Fusions	Non-small cell lung cancer	Selpercatinib	Phase I/II. LIBRETTO-001. NCT03157128. N=316 (247 pretreated, 69 naive). Selpercatinib in RET fusion-positive NSCLC. ORR 62% pretreated, 83% naive. Median DoR 31.6 months pretreated, 20.3 months naive. Median PFS 26.2 months pretreated, 22.0 months naive. Median OS 47.6 months pretreated, not reached naive. 3-year OS 57% pretreated, 66% naive. CNS-ORR 85%, CNS-PFS 11.0 months.	39983053
GIMR	2022-01-19	FL/DK/CG	3	RET	Oncogenic mutations (germline)	Paraganglioma; Phaeochromocytoma	Sunitinib	Phase 2. SNIPP trial. N=25 enrolled. Overall DCR was 83%. Three patients with germline SDHB, SDHA, or RET mutations achieved RECIST objective response.	31105270
GIMR	2022-01-12	FL	3	ROS1	Fusion	Non-small cell lung cancer	Crizotinib	Phase 2. NCT02499614. Cohort A. N=26. In previously treated NSCLC patients, the ORR was 70% (17/26), including 1 CR. Median PFS 22.8 months. OS rate at 12 month 79%. ROS1 rearrangement defined by FISH in >= 15% of cells	31416808
GIMR	2026-03-04	FL	3	ROS1	Fusion	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations.	40554742
GIMR	2022-01-21	FL	3	ROS1	Fusion	Solid tumours	Repotrectinib	Phase 1. NCT03093116, ongoing clinical trial. Confirmed ORR 90% in 10 treatment-naive patients. In 18 pre-treated patients, the ORR was 28% with DOR of 10.2 months. Repotrectinib was shown to be active in patients with brain metastases.	10.1200/JCO.2019.37.15_suppl.9011
GIMR	2020-06-23	FL	3	ROS1	Fusion, G2032R	Non-small cell lung cancer; Solid tumours	Repotrectinib	Exceptional Phase 1 activities (ORR 90%)	10.1200/JCO.2019.37.15_suppl.9011
GIMR	2025-06-13	FL	3	ROS1	Fusions	Non-small cell lung cancer	Brigatinib	Phase 2. Barossa study. N=51. Brigatinib showed an ORR of 71% and median PFS of 12.0 months in TKI-naive NSCLC patients, and 32% ORR with 7.3 months median PFS in crizotinib-pretreated NSCLC patients.	39018589
GIMR	2020-05-06	FL	3	ROS1	Fusions	Non-small cell lung cancer	Ceritinib	Phase 2 trial. Ceritinib demonstrated clinical activity in patients with ROS1-rearranged NSCLC, with ORR of 62%, median PFS of 9.3 months, and median OS of 24 months, in patients with ROS1-rearranged NSCLC who develop resistance to crizotinib.	28520527
GIMR	2022-01-19	FL/DK/CG	3	SDHA	Oncogenic mutations (germline)	Paraganglioma; Phaeochromocytoma	Sunitinib	Phase 2. SNIPP trial. N=25 enrolled. Overall DCR was 83%. Three patients with germline SDHB, SDHA, or RET mutations achieved RECIST objective response.	31105270
GIMR	2025-07-30	FL	3	SDHB	Oncogenic mutations (germline)	Paraganglioma; Phaeochromocytoma	Cabozantinib	Phase 2. Natalie Trial. NCT02302833. N=17. Cabozantinib achieved ORR of 25% (95% CI 7.3–52.4) in 16 evaluable patients with metastatic phaeochromocytoma/paraganglioma (MPPGs). Note the responses are independent of SDHB pathogenic variants, catecholamine secretion, or noradrenaline transporter expression.	38608693
GIMR	2022-01-19	FL/DK/CG	3	SDHB	Oncogenic mutations (germline)	Paraganglioma; Phaeochromocytoma	Sunitinib	Phase 2. SNIPP trial. N=25 enrolled. Overall DCR was 83%. Three patients with germline SDHB, SDHA, or RET mutations achieved RECIST objective response.	31105270
GIMR	2025-06-04	FL	3	SEZ6	Protein expression	High-grade well-differentiated neuroendocrine tumour; Neuroendocrine carcinoma; Solid tumour	ABBV-706	Phase 1. NCT05599984. ABBV-706, a SEZ6-targeting antibody-drug conjugate, showed preliminary efficacy in high-grade neuroendocrine neoplasms (NENs) with an overall objective response rate of 31% (20/64) and median progression-free survival of 6.8 months.	10.1200/JCO.2025.43.16_suppl.105
GIMR	2022-06-08	FL	3	SMARCB1	Loss of protein expression, Oncogenic mutations	Atypical teratoid rhabdoid tumor; Chordoma; Epithelioid sarcoma	Tazemetostat	NCT02601937. Phase 1 (Paediatric). N=47. ORR was 17% (2 CR and 6 PR) in INI-negative tumours in the pediatric population (atypical teratoid rhabdoid tumor, chordoma and epithelioid sarcoma).	10.1200/JCO.2020.38.15_suppl.10525
GIMR	2020-06-09	FL	3	SMARCB1	Oncogenic mutations	Epithelioid sarcoma	Tazemetostat	Phase 2 basket study. NCT02601950. N=62. Tazemetostat showed clinical activity in patients with advanced epithelioid sarcoma with loss of INI1/SMARCB1, with an ORR of 15%, median PFS of 5.5 months, and median OS of 19.0 months. In Cohort 6 (N=44) Tazemetostat showed an ORR of 11.4% with 1 CR and 4 PR, and 17 patients had SD, resulting in a median PFS of 3.7 months and median OS of 16.6 months.	33035459, 10.1200/JCO.2020.38.15_suppl.11564
GIMR	2021-05-28	FL	3	SSTR2	Protein expression	Pancreatic neuroendocrine tumour; Neuroendocrine tumour	Lenvatinib	Phase 2 TALENT trial. In patients with pancreatic and gastrointestinal NET previously treated with somatostatin analogues and/or targeted agents, Lenvatinib resulted in 30% with DOR of 21.5 months. Somatostatin receptor positivity is implied.	33945297
GIMR	2021-09-03	FL	3	TACSTD2	Protein expression, Overexpression	Triple-negative breast cancer	Sacituzumab Govitecan	Pre-specified biomarker analysis from the phase 3 ASCENT trial. High and medium Trop2 expression were associated with higher magnitude of PFS and OS benefit versus standard-of-care chemotherapy.	34116144
GIMR	2020-07-10	FL	3	TNFRSF17	Protein expression	Multiple myeloma	Belantamab mafodotin	Phase 2 DREAMM-2 study. NCT03525678. N=196. Belantamab mafodotin showed anti-myeloma activity with overall response rates of 31% and 34% in the 2.5 mg/kg and 3.4 mg/kg cohorts respectively in patients with relapsed or refractory multiple myeloma.	31859245
GIMR	2025-06-29	FL	3	TNFRSF8	Protein expression	Peripheral T-cell lymphoma	Acimtamig	Phase 2 study. NCT04101331. N=108. In patients with CD30-positive relapsed or refractory peripheral T-cell lymphomas, acimtamig exhibited an ORR of 32.4% with a CD30 positivity determined by Ber-H2 targeted IHC with CD30 expression confirmed in ≥1% of tumor cells, and a median DoR of 2.3 months.	39531538
GIMR	2020-09-21	FL	3	TP53	Alteration	Chronic lymphocytic leukaemia	Ibrutinib	Retrospective biomarker analysis of Phase 2 trial NCT01500733 (N=34) showed ibrutinib as first-line therapy for CLL with TP53 alterations achieved 61% progression-free survival and 79% overall survival at 6 years, with median time to disease progression of 53 months and 30% complete response rate.	32726539
GIMR	2022-06-06	FL	3	TP53	NOT Oncogenic mutations	Merkel cell carcinoma	Navtemadlin	Phase 1/2. NCT03787602. Single-agent navtemadlin showed a confirmed ORR of 25% in metastatic Merkel cell carcinoma that was previously treated by PD-1 inhibition.	10.1200/JCO.2022.40.16_suppl.9506
GIMR	2020-02-02	FL	3	TP53	Oncogenic mutations	Myelodysplastic syndrome; Acute myeloid leukaemia	Eprenetapopt + Azacitidine	Ph I/II study. N=55 ORR 71%; CR 44%	33449813
GIMR	2021-03-31	FL	3	TP53	Oncogenic mutations	Uterine serous carcinoma	Adavosertib	Single arm Phase 2 trial with adavosertib in USC with TP53 alterations (predefined hypothesis). ORR 29% with PFS at 6 months 47%. Note: TP53 mutation was prespecified in the hypothesis of study, although TP53 alone is likely insufficient for predicting sensitivity to WEE1 inhibition.	33705205
GIMR	2026-02-24	FL	3	TP53	Y220C	Ovarian cancer; Solid tumours	Rezatapopt 	Phase 1. PYNNACLE. NCT04585750. N=77. Across all dose groups, rezatapopt established. Overall response rate 20% (30% in KRAS wild-type tumors at ≥1150 mg), including confirmed responses in ovarian and breast cancers; all responders harbored TP53 Y220C and wild-type KRAS.	39945593
GIMR	2021-09-20	FL	3	TP53+KRAS	TP53:Oncogenic mutations AND KRAS:G12, TP53:Oncogenic mutations AND KRAS:G13	Colorectal adenocarcinoma	Adavosertib	FOCUS4-C: Phase 2 KRAS and TP53 mutant treatment-refractory CRC. N=69. Adavosertib was associated with PFS improvement  (primary endpoint) over active monitoring (3.6 v 1.9 months). OS not significantly improved. PFS Benefits were seen in the subgroups of left-sided primary tumour location and KRAS codon 12/13.	34538072
GIMR	2021-06-15	FL	3	Tumour microenvironment	Immunomodulatory subtype	Triple-negative breast cancer	Famitinib + Camrelizumab + Nab-paclitaxel	Phase 2. FUTURE-C-PLUS. N=46: The immunomodulatory (IM) subtype is defined by CD8+ IHC in tumour >= 10%. ORR: 81% in patient (39/48 in ITT population).	10.1200/JCO.2021.39.15_suppl.1007
GIMR	2021-04-13	FL	3	Tumour Mutational Burden	High	Breast cancer	Pembrolizumab	TAPUR: N=28, HTMB ranging from 9 to 37 mutations/megabase. ORR 21%. Median PFS 10.6 weeks. Both TNBC and non-TNBC were included. 	33844595
GIMR	2022-05-30	FL	3	Tumour Mutational Burden	High	Colorectal adenocarcinoma	FOLFOXIRI + Bevacizumab + Atezolizumab	NCT03721653. Exploratory analysis from Phase 3 AtezoTRIBE. In experimental group, significant PFS benefit (HR:0.23) was seen in patients with high TMB treated with atezolizumab plus FOLFOXIRI and bevacizumab.	10.1016/S1470-2045(22)00274-1
GIMR	2024-06-18	FL	3	Tumour Mutational Burden	High	Endometrial cancer; Neuroendocrine carcinoma; Non-small-cell lung cancer; Pancreatic cancer; Sarcoma; Gastrooesophageal carcinoma; Cervical cancer; Cancer of unknown primary; Prostate cancer; Non-melanoma skin cancer	Atezolizumab	Phase 2. TAPISTRY trial. NCT04589845. N=150. Atezolizumab showed ORR of 23% (TMB ≥16 mut/Mb) and 20% (TMB ≥13 mut/Mb), with median PFS of 2.8 months and 2.7 months, respectively, in patients with TMB-high solid tumors. TMB was assessed by Foundation One CDx. Tumour types with n>=4 and ORR >=20 are listed. The correlation with MSI-H, dMMR, and PD-L1 status were not reported.	10.1200/JCO.2024.42.17_suppl.LBA2509
GIMR	2020-04-25	FL	3	Tumour Mutational Burden	High	Non-small cell lung cancer	Durvalumab + Tremelimumab	Phase 3 MYSTIC trial. NCT02453282. N=1118. In patients with blood tumor mutational burden ≥20 mutations per megabase, durvalumab plus tremelimumab demonstrated improved OS (21.9 vs 10.0 months). Overall, durvalumab showed no OS improvement over chemotherapy (16.3 vs 12.9 months) in patients with ≥25% PD-L1 tumor cell expression. Similarly, durvalumab plus tremelimumab did not improve OS or PFS compared to chemotherapy. 	32271377
GIMR	2021-04-07	FL	3	Tumour Mutational Burden	High	Non-small cell lung cancer	Ipilimumab + Nivolumab + Carboplatin + Pemetrexed; Ipilimumab + Nivolumab + Cisplatin + Pemetrexed; Ipilimumab + Nivolumab + Carboplatin + Paclitaxel	Checkmakte 9LA: In non-EGFR/ALK-altered NSCLC, the prespecified subgroup analysis showed that high tumour TMB (at cut off of 10 mut/MB) is associated with high ORR in the chemo + IO group (46 v 28%), also mPFS (8.9 vs 4.7mo) and OS (15.0 vs 10.8 mo). Similar benefit was was also observed in bTMB at the 16 and 20 mut/MB thresholds.	10.1016/S1556-0864(21)01940-7
GIMR	2026-03-05	FL	3	Tumour Mutational Burden	High	Solid tumours	Nivolumab + Ipilimumab; Nivolumab	Phase 2. CheckMate 848. NCT03668119. N=201. Randomized open-label. Advanced or metastatic solid tumors with high tumor mutational burden (tTMB-H or bTMB-H). Refractory to standard therapies. Randomized 2:1 to nivolumab plus ipilimumab or nivolumab monotherapy. In tTMB-H patients, ORR was 38.6% with nivolumab plus ipilimumab versus 29.8% with nivolumab monotherapy. In bTMB-H patients, ORR was 22.5% with nivolumab plus ipilimumab versus 15.6% with nivolumab monotherapy. Early and durable responses observed with combination therapy.	39107131
GIMR	2020-09-25	FL	3	Tumour Mutational Burden	High	Solid tumours except Colorectal adenocarcinoma	Pembrolizumab	Not TGA approved. KEYNOTE-158. FDA approved although overall Tier 3, H v nonH: ORR 29% v 6% in a Phase 2 study.	32919526
GIMR	2024-09-14	FL	3	VTCN1	Protein expression	Solid tumours	Puxitatug samrotecan	Phase 1/2a. BLUESTAR. NCT05123482. N=46. AZD8205 showed preliminary efficacy with 21% in heavily pre-treated patients with advanced and metastatic solid tumours. CtDNA reductions were seen across tumour types.	10.1016/j.annonc.2024.08.673
GIMR	2022-08-08	FL/JG	4	ABL1	BCR-ABL1 Fusion	Glioblastoma	Imatinib	Case report. Treatment with imatinib in a Glioblastoma harbouring BCR-ABL1 fusion resulted decrease in KI-67 and clinical stable disease. 	34485806
GIMR	2025-04-23	FL	4	ABL1	BCR-ABL1 fusion AND T315I AND E355G	Chronic myelogenous leukaemia	Ponatinib + Asciminib	Case report. Ponatinib and asciminib combination therapy effectively overcame BCR-ABL1 T315I/E355G compound mutant resistance in a CML patient, with complete haematologic response achieved within 2 weeks.	39214096
GIMR	2020-05-15	FL	4	AKT1	E17K	Breast cancer	Capivasertib; Capivasertib + Fulvestrant	Phase 1. NCT01226316. Capivasertib showed clinical activity as monotherapy (ORR 20%) and in combination with fulvestrant (ORR 36% in fulvestrant-pretreated and 20% in fulvestrant-naive patients) in heavily pretreated AKT1(E17K)-mutant ER-positive metastatic breast cancer patients.	32312891
GIMR	2025-03-06	FL	4	AKT1	E17K	Breast cancer; Endometrial cancer	ALTA-2618	Preclinical study. The mutant-selective inhibitor of AKT1 E17K induced tumor regressions in multiple PDX models of breast and endometrial cancer models.	10.1158/1538-7445.AM2024-LB173
GIMR	2025-06-22	FL	4	AKT1	E17K	Head and neck squamous cell carcinoma	Ipatasertib	Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers.	10.1200/JCO.2024.42.16_suppl.3092
GIMR	2020-05-15	FL	4	AKT1	E17K	Solid tumours	Capivasertib	Phase 1 Expansion cohort of AZD5363. Activity was seen in AKT1 E17K-mutant cancers (n=52) with median PFS of 5.5, 6.6, and 4.2 months in ER+ breast, gynecologic, and other solid tumors, respectively, and responses were associated with AKT1 E17K mutant allele imbalance and coincident PI3K pathway hotspot mutations.	28489509
GIMR	2023-11-08	FL	4	AKT1	LAMTOR1-AKT1 fusion	Solid tumour	Ipatasertib	Case report. A paediatric patient with histopathologically indeterminate epithelioid neoplasm harbouring a novel fusion LAMTOR1-AKT1 treated with ipatasertib resulted in dramatic tumour regression. Confirmation in the in vitro models confirmed the fusion led to activation of AKT1.	30877085
GIMR	2021-03-31	FL	4	AKT1	Oncogenic mutations	Breast cancer	Ipatasertib + Paclitaxel	HR-positive disease. IPATunity130 Cohort B. ORR 47% in both ipatasertib and placebo arms but there was no significant difference in median PFS (ipatasertib vs placebo: 9.2 vs 8.5 mo). Ongoing follow-up.	10.1016/j.annonc.2020.08.385
GIMR	2021-06-18	FL	4	AKT1	Oncogenic mutations	Solid tumours	Sapanisertib + Metformin	Phase 1 trial. NCT03017833. N=30. Sapanisertib + metformin showed anti-tumor activity in patients with mTOR/AKT/PI3K pathway alterations, including 4 patients achieving partial response, 3 of whom had PTEN mutations and 1 had AKT and mTOR mutation.	10.1200/JCO.2021.39.15_suppl.3017
SuboKB	2020-04-16	ST	4	AKT2	Oncogenic mutations	Solid tumours	CCT128930	Preclinical study. CCT128930, a novel AKT inhibitor, exhibited antiproliferative activity, inhibited AKT substrates phosphorylation, and caused G1 arrest in PTEN-null U87MG cells, with antitumor activity observed in U87MG and BT474 human breast cancer xenografts.	21191045
GIMR	2021-06-18	FL	4	AKT2	Oncogenic mutations	Solid tumours	Sapanisertib + Metformin	Phase 1 trial. NCT03017833. N=30. Sapanisertib + metformin showed anti-tumor activity in patients with mTOR/AKT/PI3K pathway alterations, including 4 patients achieving partial response, 3 of whom had PTEN mutations and 1 had AKT and mTOR mutation.	10.1200/JCO.2021.39.15_suppl.3017
SuboKB	2020-04-16	ST	4	AKT2	Oncogenic mutations	Solid tumours	Uprosertib	"Preclinical study. Selectivity profiling of Akt inhibitors GSK690693 and GSK2141795.	23795919
SuboKB	2020-04-16	ST	4	AKT3	Oncogenic mutations	Breast cancer	Uprosertib	Preclinical study. Novel AKT inhibitors (GSK2110183 and GSK2141795) showed anti-tumor effects in mouse tumor models, with enhanced efficacy when combined with MEK inhibitor (GSK2110212; trametinib) in KRAS-driven pancreatic cancer models.	24978597
GIMR	2020-05-25	FL	4	ALK	A348D, F856S	Acute lymphoblastic leukaemia	Crizotinib; Ceritinib; Brigatinib	Preclinical study. ALK mutations identified in leukemia patients were potently transforming and conferred sensitivity to ALK kinase inhibitors.	26032424
GIMR	2020-04-25	FL	4	ALK	Amplification	Non-small cell lung cancer	Ceritinib	Retrospective study. ALK-positive NSCLC. Median PFS on sequential crizotinib and ceritinib was 17.4 months, with ceritinib showing significant antitumor activity even after crizotinib treatment, and no difference in PFS on ceritinib between patients with or without ALK resistance mutations. Updated 2025-06-14	25724526
GIMR	2025-04-30	FL	4	ALK	C1156Y, I1171N, V1180L, L1196Q, L1198F, D1203N, S1206F, S1206Y, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Ensartinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	4	ALK	C1156Y, L1196Q, L1196Q, L1198F, G1202del, S1206F, S1206Y, E1210K, G1269A, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Zotizalkib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2022-09-19	FL	4	ALK	EML4-ALK fusion, F1174L, R1275Q, L1196M, C1156Y	Solid tumours	Alectinib	Preclinical study. CH5424802 (Alectinib), a potent and selective ALK inhibitor, showed antitumor activity against ALK-driven cancers, including NSCLC and ALCL, and inhibited the resistant gatekeeper mutant ALK L1196M.	21575866
GIMR	2024-07-03	FL	4	ALK	EML4-ALK fusion, NPM-ALK fusion, C1156Y, L1196M, I1171T, F1197M, G1269A, S1206Y, R1275Q, F1174L	Solid tumours; Non-small cell lung cancer; Anaplastic large cell lymphoma	APG-2449	Preclinical study. APG-2449 is a ALK/ROS1/FAK inhibitor	35820889
GIMR	2023-08-10	FL	4	ALK	F1174C	Prostate small cell carcinoma	Alectinib	Case report. In one case of prostate small cell carcinoma harbouring ALK F1174C, Alectinib led to stable disease for more than 6 months, improved symptoms, and in ctDNA vaf.	29559559
GIMR	2022-01-21	FL	4	ALK	F1174V, F1174L, G1128A, I1171N, R1192P, F1245C, R1275Q, Y1278S	Neuroblastoma	Repotrectinib; Crizotinib	Cell line study. Repotrectinib reduced the growth of ALK transfected PC12 cells that harbour constitutively active ALK mutations.	32269053
GIMR	2020-06-06	FL	4	ALK	F1245C	Neuroblastoma	Alectinib	Case report. Refractory metastatic neuroblastoma harboring an ALK F1245C mutation achieved a partial response with alectinib monotherapy, with significant symptom improvement and reduction in tumor size. Resistance eventually developed after 16 weeks.	29603581
GIMR	2025-05-31	FL	4	ALK	Fusion	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed  activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2021-10-13	FL	4	ALK	Fusion	Solid tumours; Histiocytosis; Renal cell carcinoma	Crizotinib; Alectinib	Comprehensive genomic profiling of 114,200 clinical cases revealed ALK fusions in 0.8% of cases, with 22.9% of ALK fusions occurring in non-NSCLC tumors, which responded to anti-ALK targeted therapies.	29079636
GIMR	2020-04-25	FL	4	ALK	Fusion AND Amplification, L1196M, C1156Y, F1174L, F1174V, G1202R, G1269A, I1171T, I1171S, L1152R, L1152V, T1151R, T1151M, L1198F, S1206F, D1203E	Non-small cell lung cancer	Ensartinib	Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.	31628085
GIMR	2022-06-15	FL	4	ALK	Fusion AND Amplification, L1196M, E1408V, T1151M	Non-small cell lung cancer	Brigatinib	Phase 1/2 and Phase 2 (ALTA) trials. Brigatinib showed substantial activity in crizotinib-resistant ALK+ NSCLC patients with ALK fusion-positive status (cORR 57%) and in those with secondary ALK mutations (cORR 50%), with complex mutation patterns associated with resistance in 25% of patients at end of treatment.	10.1200/JCO.2017.35.15_suppl.9065
GIMR	2022-01-21	FL	4	ALK	Fusion, G1202R	Solid tumours	Repotrectinib	Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models.	30093503
GIMR	2021-04-24	FL*	4	ALK	Fusion, T1151M, T1151_L1152insT, L1152R, L1152P, C1156Y, I1171N, F1174L, F1174S, F1174C, V1180L, L1196M and L1198F, L1198F and C1156Y, L1198F, G1202R and L1198F, G1202R, G1202del, D1203N, D1203N and E1210K, S1206R, E1210K and S1206C, E1210K, L1196M, F1245C, G1269A, S1269S, R1275Q	Non-small cell lung cancer	Zotizalkib	Cell line assays comparing Zotizalkib against approved ALK inhibitors	10.1158/1538-7445.AM2020-5226
GIMR	2020-06-06	FL	4	ALK	Fusions	Inflammatory myofibroblastic tumour	Alectinib	Case report. Dramatic response to alectinib observed in a patient with inflammatory myofibroblastic tumor harboring ALK fusion gene.	28977547
GIMR	2020-06-06	FL	4	ALK	Fusions	Inflammatory myofibroblastic tumour	Alectinib	Case report. A patient with inflammatory myofibroblastic tumor (IMT) harboring a novel SQSTM1-ALK fusion gene demonstrated a marked and durable response to alectinib, sustaining for 17 months without significant adverse events.	30790150
GIMR	2020-06-06	FL	4	ALK	Fusions	Inflammatory myofibroblastic tumour	Ceritinib	Case report. A patient with unresectable ALK-negative inflammatory myofibroblastic tumor (IMT) carrying a TFG-ROS1 fusion experienced partial response to ceritinib, a ROS1 inhibitor.	31805529
GIMR	2020-05-31	FL	4	ALK	Fusions	Solid tumours	Crizotinib; Alectinib		10.1200/JCO.2020.38.15_suppl.104
GIMR	2025-04-30	FL	4	ALK	G1202R, T1151M, T1151insT, C1156Y, I1171N, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Neladalkib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2020-04-27	FL	4	ALK	L1198F	Non-small cell lung cancer	Crizotinib	Case report. A patient with metastatic ALK-rearranged lung cancer developed resistance to crizotinib due to C1156Y mutation, responded to lorlatinib, but upon relapse, acquired L1198F mutation, resensitizing the tumor to crizotinib, allowing for successful retreatment with crizotinib.	26698910
GIMR	2020-05-31	FL	4	ALK	Oncogenic mutations	Solid tumours	Ceritinib		10.1200/JCO.2020.38.15_suppl.10505
GIMR	2020-04-16	FL	4	ALK	Oncogenic mutations	Solid tumours	Entrectinib; Ceritinib	Case report of a 57-year-old male patient with ALK-rearranged inflammatory myofibroblastic tumor showing drastic responses to two ALK inhibitors, ASP3026 and ceritinib (LDK378), with serum hyaluronan levels used to monitor treatment efficacy.	27003761, 25322323, 26372962, 27565932
GIMR	2020-05-31	FL	4	ALK	Oncogenic mutations, F1174L, F1174C, R1275Q, F1245L, F1245V, F1245Y, D1276_R1279, amplification	Neuroblastoma	Lorlatinib		10.1200/JCO.2020.38.15_suppl.10504
GIMR	2021-08-31	FL	4	ALK	SPECC1L-ALK fusion	High-grade gliomas	Lorlatinib	Case of a paediatric high-grade glioma harbouring SPECC1L-ALK fusion demonstrating deep and durable response to lorlatinib.	34407349
GIMR	2021-08-19	FL	4	ALK	STRN-ALK fusion	Breast Cancer	Alectinib	Case report. A patient with STRN-ALK fusion-positive breast cancer responded to alectinib, with initial partial response followed by mixed response and eventual progression at 2 months, highlighting the potential benefit of comprehensive genomic profiling in identifying actionable targets in advanced breast cancer.	34423228
GIMR	2020-06-13	FL	4	ALK	T1151, C1156Y, F1174C, F1174L, F1174V, G1269A, L1196M, S1206R	Non-small cell lung cancer	Ensartinib	Review. New generation anaplastic lymphoma kinase inhibitors in NSCLC, discussing the development of II and III generation TKIs to overcome acquired resistance to crizotinib and manage CNS localizations.	31857951
GIMR	2025-04-30	FL	4	ALK	T1151M, C1156Y, F1174L, D1203N, S1206F, S1206Y, E1210K, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Alectinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	4	ALK	T1151M, F1174L, V1180L, L1196M, L1196Q, S1206F, S1206Y, G1269A, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Ceritinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	4	ALK	T1151M, F1174L, V1180L, L1198F, G1202del, I1171N and L1198F, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Crizotinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	4	ALK	T1151M, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, G1269A, I1171N and L1198F, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Brigatinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	4	ALK	T1151M, T1151insT, C1156Y, F1174L, V1180L, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, F1174L, Exon 2–3 deletion, Exon 2-17 deletion	Solid tumours; Non-small cell lung cancer	Lorlatinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2022-03-09	FL	4	ALK	VKORC1L1-ALK fusion, T1151K	Non-small cell lung cancer	Alectinib	Case report. A lung cancer patient with a novel VKORC1L1-ALK fusion and an acquired ALK T1151K mutation showed a response to alectinib, demonstrating its clinical activity against the T1151K mutation.	30519133
GIMR	2025-04-23	FL	4	APC+PIK3CA	APC:Oncogenic mutations AND PIK3CA:Oncogenic mutations	Colorectal adenocarcinoma	G007-LK; RK-582	Preclinical study. Tankyrase inhibitor sensitivity in colorectal cancer cells correlates with APC/PIK3CA mutations and beta-catenin status, suggesting potential predictive biomarkers.	37968472
SuboKB	2020-04-16	FL	4	AR	Alteration	Solid tumours	Androgen receptor antagonist; GnRH agonist; CYP17A1 inhibitor		25595907
GIMR	2024-11-22	FL	4	AR	AR-FL; AR-V7	Prostate cancer	BWA-522	Preclinical study. Orally bioavailable PROTAC degrader targeting N-terminal domain of androgen receptor inducing degradation of both AR-FL and AR-V7 in prostate cancer cell line and rowth inhibition in LNCaP xenograft model.	37556600
GIMR	2023-12-27	FL	4	AR	AR-V7	Prostate cancer	EPI-7386		10.1093/annonc/mdz244.065
SuboKB	2020-04-23	FL	4	AR	AR-V7, F877L, L702H	Prostate cancer	Mivebresib	Preclinical study. BET inhibitor ABBV-075 inhibited transcription activation downstream of AR and TMPRSS2:ETS fusion proteins, showing antiproliferative activity in models with resistance to second-generation antiandrogens and AR splice variant AR-V7 and gain-of-function mutations, F877L and L702H.	27707886
GIMR	2025-01-12	FL	4	AR	L702H, L702H and H875Y, L702H and T878A, L702H and W742C and T878A, T878A, W742C and T878A	Prostate cancer	BMS-986365	Phase 1. CC-94676-PCA-001. NCT04428788. In patients with progressive mCRPC, BMS-986365 showed activity in heavily pretreated patients and overcome resistance to current ARPIs, regardless of AR LBD mutation status.	39293515
POTTR	2020-04-16	FL	4	AR	Protein expression	Glioma	Enzalutamide	Preclinical study. Androgen receptor (AR) was amplified in 27% of glioblastoma specimens from men and 38.2% from women, with overexpression of AR-RNA and AR-protein in 93% and 56% of samples, respectively; AR antagonists induced concentration-dependent death in glioblastoma cell lines, and enzalutamide reduced tumor volume by 72% in human glioma xenografts.	29731997
GIMR	2024-11-22	FL	4	AR	Wildtype, Amplifications, Oncogenic mutations	Prostate cancer	CC-94676	Phase 1. NCT04428788. in metastatic castration-resistant prostate cancer patients, CC-94676 34% of patients achieved PSA30 across all dose levels.	10.1200/JCO.2024.42.4_suppl.134
GIMR	2021-06-07	FL	4	ARAF	K336M, K336M and G387D, R362H and G387D	Solid tumours	Belvarafenib	K336M is a kinase-dead mutation but remains sensitive to belvarafenib	33953400
GIMR	2020-04-16	FL	4	ARAF	Oncogenic mutations, P216A	Histiocytosis	Cobimetinib	Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations. No cases with isolated ARAF responded to cobimetinib	30867592
GIMR	2020-06-02	FL	4	ARAF	S214C	Non-small cell lung cancer	Sorafenib	Case report and preclinical study. ARAF S214C mutation identified in a lung adenocarcinoma patient with a near-complete response to sorafenib, was shown to be oncogenic and sorafenib-sensitive in cellular transformation assays.	24569458
SuboKB	2020-04-25	FL	4	ARID1A	Loss-of-function mutations	Breast cancer; Ovarian cancer	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody		29736026
GIMR	2025-01-20	FL	4	ARID1A	Oncogenic mutations	Endometrial cancer	Avelumab + Carboplatin + Paclitaxel	Phase 2. MITO END-3 trial. NCT03503786. N=125. Compared with chemotherapy alone, avelumab efficacy varied by molecular profiling with favorable PFS in MSI-H and worst in MSS/TP53 mut in first-line endometrial cancer therapy. Significant interactions in PFS were observed in patients with ARID1A and PTEN mutations.	38704093
GIMR	2025-02-16	FL	4	ARID1A	Oncogenic mutations	Gastric cancer	Capivasertib	Preclinical study. AKT inhibition showed synthetic lethality in ARID1A-deficient gastric cancer cells via pyroptosis induction through Caspase-3/GSDME pathway activation.	39003371
SuboKB	2020-04-25	FL	4	ARID1A	Oncogenic mutations	Ovarian clear cell carcinoma	Dasatinib	Dasatinib inhibits YES1, which is addicted in ARID1A-deficient tumours	27364904
SuboKB	2020-04-25	FL	4	ARID1A	Oncogenic mutations	Ovarian clear cell carcinoma	GSK126	Preclinical study. EZH2 inhibition showed synthetic lethality in ARID1A-mutated ovarian cancer cells, with regression of ARID1A-mutated ovarian tumors in vivo.	25686104
POTTR	2020-04-16	FL	4	ARID1A	Oncogenic mutations	Ovarian clear cell carcinoma	Molibresib; JQ1	Preclinical study. ARID1A mutation sensitises ovarian clear cell carcinomas to BET inhibitors, causing lethal interaction and inhibiting proliferation in cell lines, xenografts, and patient-derived xenograft models.	29760405
GIMR	2022-02-09	FL	4	ARID1A	Oncogenic mutations	Pancreatic adenocarcinoma	Pembrolizumab; Durvalumab; Atezolizumab; Nivolumab	Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.	34375311
GIMR	05/10/2010	FL	4	ARID1A	Oncogenic mutations	Solid tumours	M6620	Phase 1 trial of ATR inhibitor M6620, achieving 1 CR in a patient with ATM loss and ARID1A mutation, and 1 PR in a platinum-refractory and PARP inhibitor-resistant BRCA1 ovarian cancer patient when combined with carboplatin.	32568634
SuboKB	2020-04-25	FL	4	ARID1A	Oncogenic mutations	Solid tumours	M6620	Preclinical study. ARID1A deficiency sensitises tumour cells to ATR inhibitors, triggering premature mitotic entry, genomic instability, and apoptosis, representing a novel synthetic lethal therapy for ARID1A mutant tumours.	27958275
SuboKB	2020-04-25	FL	4	ARID1A	Oncogenic mutations	Solid tumours	Olaparib; Veliparib; Rucaparib	Preclinical study. ARID1A deficiency impairs DNA damage checkpoint, sensitising cells to PARP inhibitors, providing a potential therapeutic strategy for patients with ARID1A-mutant tumors.	26069190
GIMR	2025-02-24	FL	4	ARID1A	Oncogenic mutations	Solid tumours	Tuvusertib	Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2.	38407317
GIMR	2020-07-02	FL	4	ARID1A	Oncogenic mutations	Urothelial carcinoma	Nivolumab; Atezolizumab	Retrospective biomarker study. ARID1A mutation and CXCL13 expression individually correlated with improved OS in mUCC patients receiving ICT, with combinatorial biomarker analysis suggesting further improved OS prediction.	32554706
GIMR	2022-02-09	FL	4	ARID1B	Oncogenic mutations	Pancreatic adenocarcinoma	Pembrolizumab; Durvalumab; Atezolizumab; Nivolumab	Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.	34375311
GIMR	2021-05-24	FL	4	ARID2	Loss-of-function mutations	Melanoma	Anti-PD-1 monoclonal antibody	ARID2 deficiency leads increased CD274 expression, increased expression of T-cell-attracting chemokines, and effectiveness of anti-PD-L1 therapy in murine melanoma model.	33333124
GIMR	2021-05-24	FL	4	ARID2	Loss-of-function mutations	Melanoma	Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody	Inactivation of genes encoding components of the PBAF complex complex sensitised mouse B16F10 melanoma cells to killing by T cells. 	29301958
GIMR	2022-11-28	FL	4	ARID2	Loss-of-function mutations, Loss of protein expression	Solid tumours	Olaparib; Rucaparib; Talazoparib	Preclinical study. PBRM1 deficiency, occurring in 40% of clear cell renal cell carcinomas, confers synthetic lethality to DNA repair inhibitors, with PARP and ATR inhibitors showing promise in PBRM1-defective cancer models.	33888468
SuboKB	2020-04-16	FL	4	ATM	Loss of protein expression	Chronic lymphocytic leukaemia	Ceralasertib		10.1158/1538-7445.AM2014-5485
GIMR	2022-06-19	FL	4	ATM	Loss of protein expression	Triple-negative breast cancer	Olaparib + Ceralasertib	Phase 2 plasmaMatch Cohort E. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS.	10.1200/JCO.2022.40.16_suppl.1024
GIMR	2021-05-24	FL	4	ATM	Loss of protein expression; Loss-of-function mutations	Solid tumours	BAY-1895344	Phase 1 study of BAY-1895344. 4 of 11 patients with ATM protein loss or loss-of-function mutations had objective response in appendiceal, endometrial, breast, and urothelial carcinomas. SD was seen in 8 patients.	32988960
GIMR	2021-06-09	FL	4	ATM	Loss-of-function mutations	Breast cancer	Olaparib	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2020-04-25	FL	4	ATM	Loss-of-function mutations	Colorectal adenocarcinoma	Olaparib	Preclinical study. ATM-deficient colorectal cancer cells are sensitive to PARP inhibitor olaparib, with enhanced sensitivity observed upon p53 depletion or ATM inhibition.	28182994
SuboKB	2020-04-16	FL	4	ATM	Loss-of-function mutations	Prostate cancer	Olaparib	Weak efficacy from TOPARP-B	26510020, 31806540
GIMR	2020-06-16	FL	4	ATM	Loss-of-function mutations	Prostate cancer	Olaparib	Case reports. 	29304353
GIMR	2020-06-16	FL	4	ATM	Loss-of-function mutations, S1905Ifs*25	Gallbladder cancer	Olaparib	Case report. A patient with gallbladder carcinoma harboring an ATM-inactivating mutation (ATM S1905Ifs*25) responded to olaparib with a progression-free survival of 13 months.	32045060
GIMR	2023-07-11	FL	4	ATM	Oncogenic mutations	Chronic lymphocytic leukaemia	Ceralasertib	Cell line and xenograft study. AZD6738 induce cell death in CLL cell lines and primary cells  with TP53 or ATM defects, where inhibition of ATR signaling led to the accumulation of unrepaired DNA damage and cell death by mitotic catastrophe in TP53- or ATM-defective CLL cells. AZD6738 sensitized TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. 	26563132
GIMR	2023-07-11	FL	4	ATM	Oncogenic mutations	Chronic lymphocytic leukaemia	Ceralasertib + Chlorambucil; Ceralasertib + Fludarabine; Ceralasertib + Bendamustine; Ceralasertib + Ibrutinib	Cell line and xenograft study. AZD6738 sensitises TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. 	26563132
GIMR	2021-06-12	FL	4	ATM	Oncogenic mutations	Pancreatic adenocarcinoma	Berzosertib + Irinotecan	Phase 2. NCT02595931. 2 responders seen in 52 patients. Both patients habour deleterious ATM mutations (E11828 and K1109*, R3008H and R1882* germline)	10.1200/JCO.2022.40.16_suppl.3012
GIMR	2021-09-09	FL	4	ATM	Oncogenic mutations	Prostate cancer	Talazoparib	TALAPRO-1. Phase 2. N=17. 2 responders. 3/6 patients had circulating tumour cell conversion (from >=5 to <5 cells per 5-7 mL of blood).	34388386
GIMR	2023-07-11	FL	4	ATM	Oncogenic mutations	Solid tumour	VE-821 + Cisplatin	Cell line study. ATR inhibition Is synthetic lethal with the ATM-p53 tumor pathway when cells are exposed to DNA-damaging agents.	21490603
GIMR	2022-07-31	FL	4	ATM	Oncogenic mutations	Solid tumours	Ceralasertib + Olaparib	Phase 2. NCT02576444. OLAPCO. 1 CR (breast cancer) and 1 prolonged SD (26 months) with ATM germline mutations seen in 5 cases. 	34527850
GIMR	2022-08-30	FL	4	ATM	Oncogenic mutations	Solid tumours	Ceralasertib + Olaparib	Xenograft study.	32444694
GIMR	2022-07-08	FL	4	ATM	Oncogenic mutations	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2025-08-08	FL	4	ATM	Oncogenic mutations, Deletion	Prostate cancer	VX-970	Preclinical study. ATM loss in prostate cancer models did not significantly increase sensitivity to PARP inhibition but robustly sensitized to ATR inhibition, suggesting ATM-altered tumors may benefit more from ATR inhibitors than PARP inhibitors.	32127357
GIMR	2023-06-14	FL	4	ATM	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer; Pancreatic adenocarcinoma; Non-small cell lung cancer	Camonsertib	Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations.	37277454
SuboKB	2020-04-16	FL	4	ATM	Protein expression	Glioblastoma	AZD1390 + Radiotherapy		29938225
SuboKB	2020-04-16	FL	4	ATM	Protein expression	Non-small cell lung cancer	AZD1390 + Radiotherapy		29938225
GIMR	2021-10-22	FL	4	ATM+TP53	ATM:Oncogenic mutations and NOT TP53:Oncogenic mutations	Solid tumours	Alrizomadlin + Pembrolizumab	Phase 2 trial (ongoing). NCT03611868. ATM mutant (with wild-type TP53) cohort N=11. ORR 0% and DCR 44%.	10.1200/JCO.2021.39.15_suppl.2506
GIMR	2023-09-04	FL	4	ATR	Oncogenic mutation	Colorectal adenocarcinoma	SN-38 + VE-822	Cell line study. Heterozygous mutation in ATR renders the cells more susceptible to SN-38 and ATR inhibition, resulting in resulting in DNA damage, depletion of RPA. Consequently, leading to replication catastrophe.	35361811
SuboKB	2020-04-16	FL	4	ATR	Overexpression	Chronic lymphocytic leukaemia	Ceralasertib		10.1158/1538-7445.AM2014-5485
GIMR	2020-12-11	FL	4	ATRX	Loss-of-function mutations	Neuroblastoma	Olaparib	Cell line study.	32846370
GIMR	2020-08-19	MK	4	ATRX	Loss-of-function mutations	Solid tumours	Adavosertib	Preclinical study. ATRX-mutant cancers identified as selectively vulnerable to WEE1 inhibition through a genome-wide CRISPR-Cas9 screen, with AZD1775 showing robust inhibition of ATRX-deficient cell lines and xenografts.	31551363
GIMR	2025-02-24	FL	4	ATRX	Oncogenic mutations	Solid tumours	Tuvusertib	Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2.	38407317
GIMR	2022-09-02	FL	4	B2M	Loss-of-function mutations, loss of protein expression	Colorectal adenocarcinoma	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Retrospective series. In metastatic CRCs, B2M mutations (and loss of B2M expression) are associated with microsatellite high disease and derive clinical benefit from immune checkpoint inhibitors.	31008436
GIMR	2025-03-02	FL	4	BAP1	Loss of protein expression, Oncogenic mutations	Mesothelioma	AZD1390 + GSK126	Preclinical study. Combination of EZH2 and ATM inhibition showed synergistic potential against BAP1-deficient mesothelioma in drug screen and xenograft experiments, indicating a potential novel treatment modality using BAP1 as a biomarker.	38519707
SuboKB	2020-04-16	FL	4	BAP1	Oncogenic mutations	Mesothelioma	EPZ011989	Preclinical study. Loss of BAP1 function leads to increased EZH2 expression, and BAP1-mutant cells are sensitive to EZH2 inhibition.	26437366
GIMR	2020-07-03	FL	4	BAP1	Oncogenic mutations	Mesothelioma	Tazemetostat	ORR 3%. DCR 51%	NCT02860286, 10.1200/JCO.2018.36.15_suppl.8515
SuboKB	2020-04-16	FL	4	BAP1	Oncogenic mutations	Solid tumours	PARP inhibitor; Niraparib	One phase 2 trial and other mechanistic studies only.	24347639, 24894717, NCT03207347
SuboKB	2020-04-16	FL	4	BAP1	Oncogenic mutations	Uveal melanoma; Mesothelioma	Panobinostat		22038994; 25970771
GIMR	2021-06-09	FL	4	BARD1	Loss-of-function mutations	Breast cancer	Olaparib; PDD00017273	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2020-05-05	FL	4	BARD1	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 1 patient only.	32343890, 32955174
GIMR	2020-04-25	ST	4	BARD1	Oncogenic mutations	Solid tumours	PARP inhibitor	Included in multiple phase 1/2 trials as part of HRR genes	30925164, 27197561, NCT02401347, NCT02489006, NCT02760849, NCT02952534, NCT02993068, NCT03207347, NCT03377556, NCT03495544, NCT03786796, NCT04171700, NCT04190667, NCT04276376
GIMR	2022-07-08	FL	4	BARD1	Oncogenic mutations	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2024-08-19	FL	4	BARD1	Oncogenic mutations (germline)	Neuroblastoma	Talazoparib	Case report. Complete response to talazoparib + irinotecan in a child with refractory neuroblastoma and germline BARD1 mutation and achieving sustained disease control for 32 months.	39141861
SuboKB	2020-05-20	FL	4	BCL2	Amplification	Small-Cell Lung Cancer	Venetoclax	Preclinical data only	29118061
SuboKB	2020-04-16	ST/FL	4	BCL2	Amplification	Solid tumours; Liquid cancers	Venetoclax		27605552, 27582059
GIMR	2020-04-25	FL	4	BCL2	Overexpression	Breast cancer	Venetoclax	HER2-negative breast cancer	25787766, 25787766, 30518523
SuboKB	2020-04-16	ST/FL	4	BCL2	Overexpression	Small-cell lung cancer	Venetoclax		25787766, 25787766, 30518523
SuboKB	2020-04-16	ST	4	BCL6	Protein expression	Breast cancer; Diffuse large B-cell lymphoma	BCL6 inhibitor		12944904, 18927431, 27482887
GIMR	2021-10-19	FL	4	BRAF	A400V, G464V, G466V, G464E, L485_P490del, N581S, L597R, K601N, G469A, N581Y, G569R	Solid tumours	LY3009120	Class II mutations. A cell line study demonstrating sensitivity to dimer inhibition.	26732095
GIMR	2022-11-29	FL	4	BRAF	Class II mutations, Class III mutations	Solid tumours	KIN-2787		10.1200/JCO.2021.39.15_suppl.3116, 10.1158/1538-7445.AM2022-2674
GIMR	2024-05-27	FL	4	BRAF	Class II mutations, Class III mutations	Solid tumours	NST-628	Preclinical study. NST-628, a pan-RAF-MEK molecular glue, demonstrated broad activity in cell line and PDX models with MAPK pathway alterations.	38588399
GIMR	2020-09-15	FL	4	BRAF	Class II mutations, G469A, L597R, K601N	Solid tumours	BGB659; TAK632; LY3009120	Class II mutation; Sensitive to Group 2 inhibitors	30559419
GIMR	2020-04-26	FL	4	BRAF	Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R	Solid tumours	MEK inhibitor + anti-EGFR monoclonal antibody	Class III mutation	28783719; 10.1200/PO.18.00195
GIMR	2020-11-03	FL	4	BRAF	Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R	Solid tumours	Vociprotafib + Cobimetinib	Phase 1.	10.1016/S0959-8049(20)31089-3
GIMR	2022-02-04	FL	4	BRAF	Class III mutations, G466V, G596R	Solid tumours	RMC-4550	SHP2 inhibition by RMC-4550 is active in cancer models with class 3 BRAF mutants, NF1 loss, or KRASG12 mutations, suppressing RAS/MAPK signaling and cell growth by disrupting SOS1-mediated RAS-GTP loading.	30104724
GIMR	2024-07-31	FL	4	BRAF	Exon 12 deletion	Solid tumours	Naporfenib	Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors.	37656784
GIMR	2021-04-07	FL	4	BRAF	F247L, G466E, G466V, Q524L, R558Q, N581I, N581S, N581T, D594G, D594N, F595L, Class III mutations	Colorectal adenocarcinoma	Cetuximab; Panitumumab	Retrospective study. ORR 37% in class III BRAF mutants in third-and-later lines treatment.	31515458
GIMR	2022-02-08	FL	4	BRAF	Fusion; MBNL2-BRAF fusion; SND1-BRAF fusion; LUC7L2-BRAF fusion	Pancreatic adenocarcinoma	Trametinib	Case series. 3 (of 4) responders.	34476331
GIMR	2020-05-15	FL	4	BRAF	Fusions	Low-grade serous ovarian cancer	Selumetinib	Case report and genomic analysis. A patient with low-grade serous ovarian cancer experienced a complete and durable response to selumetinib, with tumour harbouring a 15-nucleotide deletion in MAP2K1 gene encoding MEK1, and 82% of 28 analysed tumours had ERK pathway-activating mutations, including BRAF fusions.	26324360
GIMR	2020-05-05	FL	4	BRAF	Fusions	Melanoma	Sorafenib; Trametinib	Two cases of 55 fusion in retrospective analysis	26314551
POTTR	2020-04-16	FL	4	BRAF	Fusions	Solid tumours	FORE8394; RAF dimer inhibitor	Class II mutations. Review article	30770389
GIMR	2022-09-07	FL	4	BRAF	Fusions, FKBP15-BRAF fusion, TARDBP-BRAF fusion, AGK-BRAF fusion, SKAP2-BRAF fusion, CUL1-BRAF fusion, KIAA1549-BRAF fusion	Melanoma	GDC0623; PD0325901; Trametinib; Selumetinib; LY3009120	Cell line study. This study investigated the heterogeneous responses of six melanoma cell lines harboring BRAF fusions to RAF and MEK inhibitors. Higher expression level was correlated with resistance and fusion partners containing a dimerization domain promoted paradoxical activation of the MAPK pathway and hyperproliferation. AlphaC-IN/DFG-OUT RAF inhibitors blunted paradoxical activation and had increased therapeutic efficacy in vitro and in vivo when combined with MEK inhibitors.	31618628
GIMR	2021-02-10	FL	4	BRAF	G466V, Class III mutations	Lung adenocarcinoma	SHP099; RMC-4550	Cell line model for Class III mutations showed relative sensitivity to SHP2 inhibitors	31533235
GIMR	2020-05-15	FL	4	BRAF	K601, K601E	Melanoma	Trametinib	Phase 2 trial of Trametinib in patients with metastatic BRAF-mutant melanoma. N=97. In BRAF-inhibitor naive patients (cohort B, N=57), ORR was 25% (1 CR, 13 PR), median PFS 4.0 months, and median OS 14.2 months. One patient with BRAF K601E mutation had a confirmed PR with PFS of 32 weeks.	23248257
GIMR	2023-05-05	FL	4	BRAF	K601E	Endometrial cancer	BGB-3245	Phase 1. NCT04249843. Response seen in a patient with endometrial cancer harbouring BRAF K601E mutation	10.1158/1538-7445.AM2023-CT031
GIMR	2021-10-19	FL	4	BRAF	L485_P490del	Solid tumours	LY3009120	Class II BRAF mutations. Preclinical study. Oncogenic BRAF in-frame deletion in the alpha-C helix identified in various cancers were found to be sensitive to RAF dimer inhibitor LY3009120, which showed tumor growth regression in tumor models, whereas vemurafenib was inactive.	26732095
GIMR	2024-07-31	FL	4	BRAF	L485_P490delinsF, L485_P490delinsY	Solid tumours	Sorafenib	Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivity with RAF inhibitors.	37656784
GIMR	2020-04-16	FL	4	BRAF	L597, L597Q	Melanoma	Trametinib	Retrospective analysis of 5 patients with non-V600 BRAF mutation (K601E and L597Q) metastatic melanoma showed 3 patients achieved partial response to trametinib, with manageable toxicity and reduced phospho-ERK signalling in paired biopsies.	24933606
GIMR	2020-06-09	FL	4	BRAF	L597, L597Q, K601, K601E	Solid tumours	FORE8394	With Cobicistat	10.1158/1535-7163.TARG-17-B176, 10.1016/S0959-8049(20)31078-9
GIMR	2020-02-08	FL	4	BRAF	N486_P490del	Histiocytosis	Trametinib	Two case reports. Langerhans cell histiocytosis responders to Trametinib (1PR, 1 durable CR)	32991018
GIMR	2022-02-15	FL	4	BRAF	N486_P490del	Pancreatic adenocarcinoma	Dabrafenib	Case report. DOR to dabrafenib was 6 months.	31519698
GIMR	2022-02-15	FL	4	BRAF	N486_P490del	Pancreatic adenocarcinoma	Dabrafenib	Cell line study. Demonstrating sensitivty of Dabrafenib in the delNVTAP cell line. 	26996308
GIMR	2022-02-08	FL	4	BRAF	N486_P490del	Pancreatic adenocarcinoma	Trametinib	Case series. 1 (of 4 )responders.	34476331
GIMR	2022-02-08	FL	4	BRAF	N486_P490del	Pancreatic adenocarcinoma	Trametinib; Ulixertinib	Case report. DOR of trametinib was 5.5 months. CfDNA Response to Ulixertinib was shown.	34476331
GIMR	2025-05-18	FL	4	BRAF	N486_P490del, L485_P490del	Solid tumours	Tovorafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2024-07-31	FL	4	BRAF	N486_P490del, V487_P492delinsA	Solid tumours	Encorafenib, Dabrafenib	Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors.	37656784
GIMR	2022-09-07	FL	4	BRAF	Oncogenic mutations	Solid tumours	LY3009120	Phase 1 dose escalation and expansion study of LY3009120.	31645440
POTTR	2020-04-16	FL	4	BRAF	Oncogenic mutations	Solid tumours	LY3214996	Phase 1. NCT02857270. LY3214996, an ERK1/2 inhibitor, showed acceptable safety profile, favorable PK, and potent tumor PD inhibition in patients with advanced cancer, with tumor regression observed in 7 patients and stable disease in 4 patients.	31744895, 10.1200/JCO.2019.37.15_suppl.3001
POTTR	2020-04-16	FL	4	BRAF	Oncogenic mutations	Solid tumours	LY3214996	Phase 1. NCT02857270. LY3214996, an ERK1/2 inhibitor, tumor PD inhibition in patients with advanced cancer, with tumor regression observed in 7 patients with BRAF/non-BRAF mutant cancers.	10.1200/JCO.2019.37.15_suppl.3001
POTTR	2020-04-16	FL	4	BRAF	Oncogenic mutations	Solid tumours	LY3214996; LY3214996 + Abemaciclib	Preclinical study. LY3214996, a novel ERK1/2 inhibitor, demonstrated potent anti-tumor activity in cancer models with MAPK pathway alterations, including BRAF, NRAS, or KRAS mutations, and showed enhanced efficacy in combination with CDK4/6 inhibitor abemaciclib.	10.1158/1538-7445.AM2017-4973
GIMR	2022-01-15	FL	4	BRAF	Oncogenic mutations	Solid tumours	Ravoxertinib	Phase 1. NCT01875705. N=47. Objective response seen in two BRAF-mutant colorectal cancers. Partial metabolic responses by FDG-PET were seen in 11 of 20 patients.	31848189
GIMR	2022-01-15	FL	4	BRAF	Oncogenic mutations	Solid tumours	SCH772984	Preclinical study. ERK inhibitor SCH772984 displayed nanomolar cellular potency in tumor cells with BRAF, NRAS, or KRAS mutations and induced tumor regressions in xenograft models, including those resistant to BRAF and MEK inhibitors.	23614898
POTTR	2020-04-16	FL	4	BRAF	Oncogenic mutations	Solid tumours	Ulixertinib	Phase 1 trial. NCT01781429. N=135. Ulixertinib, an ERK1/2 kinase inhibitor, showed an acceptable safety profile and early evidence of clinical activity in NRAS- and BRAF V600- and non-V600-mutant solid tumors with partial responses observed in 14% of evaluable patients.	29247021
GIMR	2022-09-07	FL	4	BRAF	SKAP2-BRAF fusion	Melanoma	Trametinib	Case report. Partial but non-durable response to trametinib.	34167970
GIMR	2023-12-22	FL	4	BRAF	T599_V600insT	Melanoma	Dabrafenib + Trametinib	Case reports. BRAF T599dup-mutated melanoma patients showed response to BRAF and MEK inhibitors.	35319964
GIMR	2023-12-22	FL	4	BRAF	T599_V600insT	Melanoma	Vemurafenib	Phase 2. AcSé vemurafenib basket study. NCT01895643. One responder seen in melanoma harbouring T599dup	37922690
GIMR	2022-02-08	FL	4	BRAF	T599_V600insT	Pancreatic adenocarcinoma	Vemurafenib + Cobimetinib	Retrospective case series of 81 patients with RAF family-mutated pancreatic cancer showed varied responses to targeted and standard therapies across different RAF mutational subgroups: BRAF V600/Exon 15, BRAF or RAF1 fusions, and Exon 11 mutations. One case with T599 duplication had 20 weeks duration of therapy.	34476331
GIMR	2025-05-18	FL	4	BRAF	V487_P492del, N486_P490del, L485_P490del	Solid tumours	Naporafenib 	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2025-05-18	FL	4	BRAF	V487_P492del, N486_P490del, L485_P490del, G466V	Solid tumours	Exarafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2022-03-15	FL	4	BRAF	V600E	Colorectal neuroendocrine carcinoma	Dabrafenib + Trametinib	Two case reports of high-grade rectal NEC with durable response to combined BRAF and MEK inhibition with DOR of 7 and 9 months respectively.	30181415
GIMR	2021-06-07	FL	4	BRAF	V600E	Melanoma; Colorectal adenocarcinoma	Belvarafenib	NCT02405065, NCT03118817	33953400
GIMR	2023-05-05	FL	4	BRAF	V600E	Melanoma; Low-grade serous ovarian cancer; Cholangiocarcinoma	BGB-3245	Phase 1. NCT04249843. Responses seen in patients post-BRAF/MEK inhibitor.	10.1158/1538-7445.AM2023-CT031
GIMR	2023-05-05	FL	4	BRAF	V600E	Non-small cell lung cancer	Lifirafenib + Mirdametinib	Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. 	10.1158/1538-7445.AM2023-CT033
GIMR	2021-02-02	FL	4	BRAF	V600E	Pancreatic adenocarcinoma	Dabrafenib + Trametinib	Case report. Sustained response reported.	10.1200/JCO.2018.36.4_suppl.214
GIMR	2022-02-08	FL	4	BRAF	V600E	Pancreatic adenocarcinoma	Dabrafenib + Trametinib	Case series. N=2 Duration of therapy were 48 weeks and >2 years.	34476331
GIMR	2020-06-09	FL	4	BRAF	V600E	Solid tumours	FORE8394	Preclinical study. RAF inhibitor FORE8394 disrupts BRAF dimers and selectively inhibits ERK signaling in tumors driven by dimeric BRAF mutants and BRAF V600 monomers.	30559419
GIMR	2022-08-12	FL	4	BRAF	V600E	Solid tumours	SHP099 + Trametinib	Preclinical study. SHP2 inhibition combined with ERK signaling inhibition prevents adaptive resistance in ERK-dependent tumors with specific molecular profiles, such as TNBC and RAS G12 mutations, but not in those with RAS G13D, RAS Q61X, or certain BRAF V600E mutations.	30605687
GIMR	2023-05-05	FL	4	BRAF	V600E, Class II mutations, Class III mutations	Solid tumour	Exarafenib	Phase 1/1b trial. NCT04913285. Exarafenib demonstrated  clinical activity and tolerability in patients with BRAF-altered solid tumors and NRAS mutant melanoma, with a ORR 18% and SD in 47% of patients.	10.1158/1538-7445.AM2023-CT032
GIMR	2021-06-12	FL	4	BRAF	V600E, Fusion	Low-grade gliomas; High-grade gliomas; Glioneuronal tumour	Ulixertinib	Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%. Prolonged disease control (over 6 months) was seen seen in 3 patients with BRAF fusions.	10.1200/JCO.2022.40.16_suppl.3009
GIMR	2023-02-22	FL	4	BRAF	V600E, KIAA1549-BRAF fusion, Fusion	Low-grade gliomas	Ulixertinib	Preclinical study. Ulixertinib showed activity in pediatric low-grade glioma models with MAPK pathway alterations.	35882450
GIMR	2025-05-18	FL	4	BRAF	V600E, N486_P490del, L485_P490del	Solid tumours	Belvarafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2025-05-18	FL	4	BRAF	V600E, N486_P490del, L485_P490del, L597R	Solid tumours	Encorafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2020-05-15	FL	4	BRAF	V600E, V600K	Melanoma	Cobimetinib	Preclinical study. Cobimetinib demonstrates efficacy in both KRAS-driven and BRAF-mutant tumours, reflecting the distinct mechanisms of action among MEK inhibitors.	23934108
GIMR	2020-05-31	FL	4	BRAF	V600E, V600K	Melanoma	Lifirafenib	Phase 1 trial. N=131. Lifirafenib showed antitumor activity in patients with B-RAF(V600)-mutated solid tumors, including melanoma, thyroid cancer, and LGSOC, as well as K-RAS-mutated NSCLC and endometrial carcinoma.	32182156
GIMR	2020-05-31	FL	4	BRAF	V600E, V600K	Solid tumours	Lifirafenib	Phase 1 trial. N=131. Lifirafenib showed antitumor activity in patients with B-RAF(V600)-mutated solid tumors, including melanoma, thyroid cancer, and LGSOC, as well as K-RAS-mutated NSCLC and endometrial carcinoma.	32182156
GIMR	2025-05-18	FL	4	BRAF	V600E, V600K, G469A, L597R, G466V	Solid tumours	PF-07709933 	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2023-07-31	FL	4	BRAF	V600E, V600K, L597R, G469A, N581Y, G466V, G466E, Class II mutations, Class III mutations, AGK-BRAF fusion	Solid tumour	BGB-3245	Cell line study. BGB-3245 demonstrates activity against a wide range of BRAF mutations, including both class I and II mutations as well as fusions.	10.1158/1538-7445.AM2023-CT031
GIMR	2025-05-18	FL	4	BRAF	V600E, V600K, N486_P490del, L597R, G466V	Solid tumours	Plixorafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2024-09-14	FL	4	BRAF	V600E, V600K, V600R	Solid tumours; Melanoma; Pancreatic adenocarcinoma	CFT1946	Phase 1/2. NCT05668585, N=25, BRAF V600 mutant solid tumors. 1 unconfirmed partial response and 7/14 pts with stable disease or better in patients with pretreated BRAF V600 inhibitors. 8 of 11 with melanoma demonstrated tumour reduction.	10.1016/j.annonc.2024.08.679
GIMR	2023-05-05	FL	4	BRAF	ZC3HAV1-BRAF fusion	Endometrial cancer	Lifirafenib + Mirdametinib	Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. 	10.1158/1538-7445.AM2023-CT033
GIMR	2023-05-24	FL	4	BRAF+EGFR	EGFR:exon 19 deletion and BRAF:V600E	Non-small cell lung cancer	Encorafenib + Osimertinib	Preclinical study. Acquired BRAF V600E mutation identified as a resistant mechanism to osimertinib treatment in a patient with T790M, with cells showing sensitivity to BRAF V600E inhibitor and enhanced vulnerability to combination treatment with osimertinib. Updated 2025-05-27	27923714
GIMR	2021-07-08	FL	4	BRAF+MET	Amplification	Colorectal adenocarcinoma	Encorafenib + Capmatinib	Case report: MET amplification was identified as the off-target resistance mechanism to Encorafenib + cetuximab and was sensitive to incorporation of type I c-met inhibitor.	10.1200/PO.21.00107
GIMR	2023-01-18	FL	4	BRAF+MET	BRAF:V600E AND MET:amplification	Colorectal adenocarcinoma	Encorafenib + Capamatinib	Case report. BRAF V600E-mutated metastatic colorectal cancer developed secondary resistance to cetuximab, encorafenib, and binimetinib due to MET amplification, and tertiary resistance to capmatinib and encorafenib due to emergence of MET D1228N mutation and KRAS G12D.	34994629
GIMR	2021-06-09	FL	4	BRCA1	Loss-of-function mutations	Breast cancer	Olaparib; PDD00017273	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2021-03-06	FL	4	BRCA1	Oncogenic mutations	Ovarian cancer	CX-5461; CX-5461 + Olaparib	Combination of RNA polymerase I and PARP inhibitors showed synergy in Xenograft and cell line models of HR-deficient high-grade serous ovarian cancers.	32457376
GIMR	2024-06-02	FL	4	BRCA1	Oncogenic mutations	Ovarian cancer	KSQ-4279 + Olaparib	Phase 1 trial. NCT05240898. N=64. KSQ-4279, a first-in-class USP1 inhibitor, showed acceptable in combination with olaparib or carboplatin in patients with advanced solid tumours and deleterious HRR mutations; disease control rate at 16 weeks was 28%, 40%, and 29% respectively.	10.1200/JCO.2024.42.16_suppl.3005
GIMR	2023-01-25	FL	4	BRCA1	Oncogenic mutations	Ovarian cancer	Olaparib + Ceralasertib	NCT03462342. In the CAPRI trial (recurrent, platinum-resistant epithelial ovarian cancer), CA125 and tumour size reductions were seen in 3 patients with BRCA1 mutations (1 germline and 2 somatic), although no radiological response was observed. No objective responses occurred in the overall cohort.	34620496
GIMR	2024-11-13	FL	4	BRCA1	Oncogenic mutations	Ovarian cancer; Prostate cancer; Pancreatic cancer	HRS-1167	Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer).	10.1200/JCO.2024.42.16_suppl.3154
GIMR	2025-02-16	FL	4	BRCA1	Oncogenic mutations	Ovarian cancer; Triple-negative breast cancer	Atezolizumab + Rucaparib	Phase 1b. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response.	38971950
GIMR	2021-09-09	FL	4	BRCA1	Oncogenic mutations	Prostate cancer	Talazoparib	TALAPRO-1. Phase 2. In BRCA1 mutants N=4. PR 2/4. 	34388386
GIMR	2023-10-25	FL	4	BRCA1	Oncogenic mutations	Solid tumour	Palacaparib	Preclinical study. PARP inhibitor (AZD9574) demonstrated potent anti-tumor activity and selectivity towards HRD+ models, showing dose-dependent efficacy in a BRCA1/2 mutant cell line, subcutaneous xenograft, and intracranial breast cancer brain metastases models.	10.1158/1538-7445.AM2022-2609
GIMR	2023-10-02	FL	4	BRCA1	Oncogenic mutations	Solid tumours	Olaparib + Durvalumab	Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 35% and ORR was 3 /16 (19%) BRCA-mutated groups, although no responders were seen in 4 patients with BRCA1 mutations.	37365284
GIMR	2022-02-08	FL	4	BRCA1	Oncogenic mutations	Solid tumours	Pamiparib + Tislelizumab	Phase 1. NCT02660034. ORR 2 of 7 patients (29%) with BRCA1/2 mutation had partial response to the pamiparib and tislelizumab combination. NB in BRCA wild-type population, the overall response rate was 25% (6/24).	31378459
GIMR	2025-02-24	FL	4	BRCA1	Oncogenic mutations	Solid tumours	Tuvusertib	Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2.	38407317
GIMR	2022-07-08	FL	4	BRCA1	Oncogenic mutations	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2025-02-16	FL	4	BRCA1	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Oxaliplatin	Retrospective analysis of the Phase 2 GOZILA trial. N=702. Putative germline BRCA1/2 mutation associated with better ORR (63.2% vs 16.2%) and PFS (HR 0.55) on platinum-containing chemotherapy.	39198618
GIMR	2023-09-27	FL	4	BRCA1	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Oxaliplatin; Cisplatin	Retrospective analysis of patients with advanced pancreatic ductal adenocarcinoma showed improved OS (21.8 vs 8.1 months) in those with germline BRCA1, BRCA2, or PALB2 mutations, particularly when treated with platinum-based chemotherapy (1-year OS: 94% vs 60%).	35135099
GIMR	2023-06-14	FL	4	BRCA1	Oncogenic mutations, Oncogenic mutations (germline)	Solid Tumours; Ovarian cancer; Head and neck squamous cell carcinoma; 	Camonsertib	Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations.	37277454
GIMR	2022-06-19	FL	4	BRCA1	Oncogenic mutations, Oncogenic mutations (germline)	Triple-negative breast cancer	Olaparib + Ceralasertib	Phase 2 plasmaMatch Cohort E. ISRCTN16945804. N=70. Olaparib + ceralasertib in TNBC patients without targetable mutation showed a ORR of 17% and median PFS of 4.3 months, not meeting pre-specified efficacy criteria. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS. 	10.1200/JCO.2022.40.16_suppl.1024
GIMR	2023-01-25	FL	4	BRCA1	Oncogenic mutations, Reversion mutations	Ovarian cancer	Olaparib + Ceralasertib	Preclinical study. Durable responses were observed with combined inhibition of PARP and ATR in platinum-resistant and acquired PARPi-resistant PDXs models of BRCA-associated high-grade ovarian serous carcinoma.	32709856
GIMR	2022-03-17	FL	4	BRCA1	Oncogenic mutations, S1253fs*10, 9435_9436delGT	Breast cancer	Olaparib	Case report. Durable response in a triple-negative breast cancer patient with somatic BRCA1 mutation and brain metastasis.	10.1200/PO.19.00012
GIMR	2021-12-09	FL	4	BRCA1	Promoter methylation	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	Rucaparib	Retrospective analysis of Part 1 of ARIEL2 trial: homozygous or hemizygous BRCA1 methylation is associated with response to rucaparib in BRCA1-methylated platinum-sensitive recurrent high-grade serous ovarian cancer. In BRCA1-methylated PDX models, silencing of BRCA1 copies predicts rucaparib response.	30266954
GIMR	2025-02-16	FL	4	BRCA1+BRCA2	NOT BRCA1:Oncogenic mutations and NOT BRCA2:Oncogenic mutations	Ovarian cancer	Rucaparib + VE-821; Rucaparib + PF-477736; Rucaparib + MK-1775	Preclinical study. ATR, CHK1, and WEE1 inhibitors induce homologous recombination repair deficiency in HR-proficient ovarian ascites models, sensitizing these cells to PARP inhibitors such as rucaparib.	38965423
GIMR	2021-06-09	FL	4	BRCA2	Loss-of-function mutations	Breast cancer	Olaparib; PDD00017273	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2024-06-02	FL	4	BRCA2	Oncogenic mutation	Ovarian cancer	KSQ-4279 + Olaparib	Phase 1 trial. NCT05240898. N=64. KSQ-4279, a first-in-class USP1 inhibitor, showed acceptable in combination with olaparib or carboplatin in patients with advanced solid tumours and deleterious HRR mutations; disease control rate at 16 weeks was 28%, 40%, and 29% respectively.	10.1200/JCO.2024.42.16_suppl.3005
GIMR	2025-02-24	FL	4	BRCA2	Oncogenic mutation	Solid tumours	Tuvusertib	Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2.	38407317
GIMR	2021-03-16	FL	4	BRCA2	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. Responder in Full eligible population	33583720
GIMR	2023-06-14	FL	4	BRCA2	Oncogenic mutations	Melanoma	Camonsertib	Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations.	37277454
GIMR	2021-03-06	FL	4	BRCA2	Oncogenic mutations	Ovarian cancer	CX-5461; CX-5461 + Olaparib	Combination of RNA polymerase I and PARP inhibitors showed synergy in Xenograft and cell line models of HR-deficient high-grade serous ovarian cancers.	32457376
GIMR	2024-11-13	FL	4	BRCA2	Oncogenic mutations	Ovarian cancer; Prostate cancer; Pancreatic cancer	HRS-1167	Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer).	10.1200/JCO.2024.42.16_suppl.3154
GIMR	2025-02-16	FL	4	BRCA2	Oncogenic mutations	Ovarian cancer; Triple-negative breast cancer	Atezolizumab + Rucaparib	Phase 1b. COUPLET trial. NCT03101280. Rucaparib-atezolizumab combination demonstrated acceptable safety and efficacy in BRCA-mutated ovarian cancer (n=14) and triple-negative breast cancer (n=5), with enhanced post-treatment PD-L1 expression and CD8 infiltration independent of response.	38971950
GIMR	2023-10-25	FL	4	BRCA2	Oncogenic mutations	Solid tumour	Palacaparib	Preclinical study. PARP inhibitor (AZD9574) demonstrated potent anti-tumor activity and selectivity towards HRD+ models, showing dose-dependent efficacy in a BRCA1/2 mutant cell line, subcutaneous xenograft, and intracranial breast cancer brain metastases models.	10.1158/1538-7445.AM2022-2609
GIMR	2022-02-08	FL	4	BRCA2	Oncogenic mutations	Solid tumours	Pamiparib + Tislelizumab	Phase 1. NCT02660034. ORR 2 of 7 patients (29%) with BRCA1/2 mutation had partial response to the pamiparib and tislelizumab combination. NB in BRCA wild-type population, the overall response rate was 25% (6/24).	31378459
GIMR	2022-07-08	FL	4	BRCA2	Oncogenic mutations	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2025-10-19	FL	4	BRCA2	Oncogenic mutations (germline)	Breast cancer	SNV1521	Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities.	ESMO25.923MO
GIMR	2025-02-16	FL	4	BRCA2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Oxaliplatin	Retrospective analysis of the Phase 2 GOZILA trial. N=702. Putative germline BRCA1/2 mutation associated with better ORR (63.2% vs 16.2%) and PFS (HR 0.55) on platinum-containing chemotherapy.	39198618
GIMR	2023-09-27	FL	4	BRCA2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Oxaliplatin; Cisplatin	Retrospective analysis. N=29. Patients with advanced PDAC and germline BRCA1, BRCA2, or PALB2 mutations demonstrate improved overall survival (21.8 months vs 8.1 months in controls) and enhanced benefit from platinum-based chemotherapy (1-year OS 94% vs 60%).	35135099
GIMR	2022-06-19	FL	4	BRCA2	Oncogenic mutations, Oncogenic mutations (germline)	Triple-negative breast cancer	Olaparib + Ceralasertib	Phase 2 plasmaMatch Cohort E	10.1200/JCO.2022.40.16_suppl.1024
GIMR	2023-01-25	FL	4	BRCA2	Oncogenic mutations, Reversion mutations	Ovarian cancer	Olaparib + Ceralasertib	Preclinical study. Durable responses were observed with combined inhibition of PARP and ATR in platinum-resistant and acquired PARPi-resistant PDXs models of BRCA-associated high-grade ovarian serous carcinoma.	32709856
GIMR	2021-04-16	FL	4	BRCA2	Reversion mutations	Pancreatic adenocarcinoma	Rucaparib	RUCAPANC: two cases of reversion mutations restoring the open reading frame near the germline mutation detected on ctDNA.	30051098
GIMR	2023-02-28	FL	4	BRCA2+PTEN	BRCA2:deletion and PTEN:deletion	Uterine leiomyosarcoma	Olaparib	Case report. A patient with metastatic uterine leiomyosarcoma harboring BRCA2, TP53, and PTEN deletions showed rapid response to olaparib after progressing on multiple prior treatments including gemcitabine-docetaxel, doxorubicin, and temozolomide.	33970096
GIMR	2022-01-15	FL	4	BRD3	BRD3-NUTM1 fusion	NUT carcinoma	Birabresib	Phase 1. NCT02259114. 3/10 patients had partial response. Trial entry criteria was determined by ectopic expression of NUT protein or confirmed BRD-NUT translocation by FISH	29733771
GIMR	2022-01-15	FL	4	BRD4	BRD4-NUTM1 fusion	NUT carcinoma	Birabresib	Phase 1. NCT02259114. 3/10 patients had partial response. Trial entry criteria was determined by ectopic expression of NUT protein or confirmed BRD-NUT translocation by FISH	29733771
GIMR	2022-01-15	FL	4	BRD4	BRD4-NUTM1 fusion	NUT carcinoma	Birabresib	Case series from compassionate access. 2 of 4 patients had rapid response to Birabresib.	26976114
JGKB	2020-04-16	FL	4	BRD4	Oncogenic mutations, fusion	Solid tumours	BET inhibitor		31273347
GIMR	2021-05-24	FL	4	BRD7	Loss-of-function mutations	Melanoma	Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody	Inactivation of genes encoding components of the PBAF complex complex sensitised mouse B16F10 melanoma cells to killing by T cells. 	29301958
SuboKB	2020-04-16	FL	4	BRIP1	Loss-of-function mutations	Prostate cancer	Rucaparib	TRITON2	32086346; NCT02952534
GIMR	2021-07-29	FL	4	BRIP1	Loss-of-function mutations	Uterine serous carcinoma	Olaparib	Case report. BRIP Q554Hfs*35. Complete response after treatment with olaparib for at least 9 months.	32923896
GIMR	2020-05-05	FL	4	BRIP1	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 3 patients only.	32343890, 32955174
GIMR	2022-07-08	FL	4	BRIP1	Oncogenic mutations	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2025-04-14	FL	4	BRIP1	Oncogenic mutations, Q554Hfs*35	Uterine serous carcinoma	Olaparib	Case report. Olaparib monotherapy resulted in a complete response lasting over nine months in a patient with BRIP1-mutated high-grade serous endometrial cancer.	32923896
SuboKB	2020-04-16	FL	4	CCND1	Amplification	Solid tumours	Ribociclib	Phase 1 study. N=132. Ribociclib demonstrated preliminary signs of clinical activity with 3 partial responses and 8 patients progression-free for >6 months.	27542767
SuboKB	2020-04-16	FL	4	CCND2	Amplification	Solid tumours	Abemaciclib		10.1158/1538-7445.AM2015-3104
SuboKB	2020-04-16	FL	4	CCND3	Amplification	Solid tumours	Abemaciclib		10.1158/1538-7445.AM2015-3104
GIMR	2020-10-01	FL	4	CCNE1	Amplification	Ovarian cancer	Dinaciclib + MK2206	Preclinical study. Cyclin E1 (CCNE1) amplification in high-grade serous ovarian cancer is selectively targeted by combined inhibition of CDK2 and AKT, showing synergistic effects and potential to overcome resistance.	27663592
GIMR	2020-11-03	FL	4	CCNE1	Amplification	Ovarian cancer	Fadraciclib	Phase 1. 1 Case of SD	10.1016/S0959-8049(20)31086-8
GIMR	2023-01-25	FL	4	CCNE1	Amplification	Ovarian cancer	Olaparib + Ceralasertib	Preclinical study. Durable responses were observed with combined inhibition of PARP and ATR in platinum-resistant and acquired PARPi-resistant PDXs models of BRCA-associated high-grade ovarian serous carcinoma.	32709856
GIMR	2020-10-01	FL	4	CCNE1	Amplification	Ovarian cancer	SNS-032	High grade ovarian cancer	26204491
GIMR	2022-03-01	FL	4	CCNE1	Amplification	Ovarian cancer; Endometrial cancer	Ceralasertib + Adavosertib	Preclinical study. CCNE1 copy numbers predict the response to low-dose WEE1i-ATRi for CCNE-amplified ovarian and endometrial carcinomas	34622231
GIMR	2025-06-13	FL	4	CCNE1	Amplification	Solid tumours	Azenosertib	Preclinical study. Azenosertib demonstrated broad antitumor activity across solid tumors in Phase I monotherapy studies. Preclinical data revealed tumor growth inhibition >60% in CCNE1-amplified models (2/2) and FBXW7-mutated models (3/5).	34423975
GIMR	2020-06-26	FL	4	CCNE1	Amplification	Triple-negative breast cancer	Adavosertib	Preclinical study. Cyclin E overexpression sensitizes triple-negative breast cancer to Wee1 kinase inhibition by AZD1775, suggesting its potential as a biomarker for monotherapy in cyclin E-high tumors and sequential combination therapy in cyclin E-low tumors.	30181387
GIMR	2022-12-20	FL	4	CCNE1	Amplification, Overexpression	Solid tumours	RP-6306	Inhibition of the PKMYT1 kinase is synthetic lethal in solid tumour vivo models harbouring amplification of CCNE1 gene.	35444283
GIMR	2026-03-04	FL	4	CCNE1	Amplification, Protein expression	Uterine serous carcinoma	Adavosertib	Phase IIb, ADAGIO. NCT04590248. N=104. Adavosertib demonstrated an ORR by BICR of 26.0% in recurrent/persistent uterine serous carcinoma previously treated with platinum-based chemotherapy. Median DoR was 4.7 months. Median PFS was 2.8 months. Biomarker analysis identified no single predictive alteration, although a trend was observed for CCNE1 amplification or high cyclin E1 protein expression.	40262070
GIMR	2022-06-19	FL	4	CCNE1	Overexpression	Triple-negative breast cancer	Olaparib + Ceralasertib	Phase 2 plasmaMatch Cohort E. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS.	10.1200/JCO.2022.40.16_suppl.1024
POTTR	2020-04-16	FL	4	CD274	Amplification	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody; immune checkpoint blockade,PD-L1-targeting 	Retrospective review suggest ORR 66%	27900363; 27942391; 29902298; 10.1200/PO.18.00017
GIMR	2022-03-09	FL	4	CD274	Amplification, protein expression	Malignant peripheral nerve sheath tumour	Nivolumab	Case report. PD-L1 > 90%. 	10.1200/PO.18.00375
GIMR	2025-07-30	FL	4	CD274	Protein expression	Anal cancer	Atezolizumab + Docetaxel + Cisplatin + Fluorouracil	Phase 2. SCARCE C17-02 PRODIGE 60. NCT03519295. N=97 (64 in Atezolizumab + mDCF vs 33 in mDCF alone). 12-month PFS 45% (90% CI 35-55) vs 43% (29-58) in group A and B; in PD-L1 CPS ≥5, 70% vs 40% (interaction p=0.051). Higher grade 3-4 adverse events in group A (61% vs 42%), primary endpoint not met. 	38547895
GIMR	2020-07-03	FL	4	CD274	Protein expression	Biliary tract cancers	Nivolumab	PD-L1 positive v negative (>=1%), PFS 10.4 v 2.3 mo	32352498
GIMR	2020-11-13	FL	4	CD274	Protein expression	Gastric cancer	Toripalimab	ORR 37% in tumours with PD-L1 expression >= 1% for TC or IC using SP142 assay (v 8%).	31236579
GIMR	2022-04-09	FL	4	CD274	Protein expression	Head and neck squamous cell carcinoma 	Pembrolizumab	Phase 3. KEYNOTE-048. NCT02358031. Unplanned subgroup analysis showed HR 1.21 for OS (pembrolizumab vs cetuximab + chemotherapy) in the PD-L1 CPS < 1 group. HR was 0.71 (pembrolizumab vs cetuximab + chemotherapy) in CPS 1-19 group. In CPS >= 20 group, pembrolizumab was associated with higher OS 14.7 vs 11.0 months (HR 0.60).	35333599
GIMR	2025-02-16	FL	4	CD274	Protein expression	Hepatocellular carcinoma	Nivolumab	Phase 1/2. CheckMate 040 trial. N=234 (80 sorafenib-naive, 154 sorafenib-experienced). ORR was 20% and 14% in sorafenib-naive and sorafenib-experienced groups, respectively. Median OS were 26.6 months and 15.1 months, respectively. Higher ORR and extended OS were observed with baseline PD-L1 ≥1% vs <1%, more pronounced in the sorafenib-experienced group.	38151184
GIMR	2022-03-26	FL	4	CD274	Protein expression	Non-small cell lung cancer	Pembrolizumab + Vibostolimab	Phase 1. First-in-human MK7684-001. In treatment-naive NSCLC, combined anti-TIGIT and anti-PD-1 antibodies achieved DCR of 83% in TPS>=1% and in 45% in TPS<1%. DCR was 32% and 45% respectively in PD-L1/PD-L1 refractory subgroup.	34800678
GIMR	2021-05-18	FL	4	CD274	Protein expression	Ovarian cancer	Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab	IMagyn050/GOG3015/ENGOT-OV39: Phase 3 trial of Chemotherapy and Bevacizumab with or without Atezolizumab. In intention-to-treat population, the median PFS was 19.5 vs 18.4 months (for IO+Chemo+Bevacizumab vs Chemo+Bevacizumab) respectively. Exploratory analysis as shown in PFS in subgroup analysis suggests that improvement in small population with IC >= 5% (HR 0.64) and TC >= 1% (HR 0.41).	33891472
GIMR	2025-06-12	FL	4	CD274	Protein expression	Solid tumours	DB-1419	Preclinical study. DB-1419, a bifunctional B7-H3xPD-L1 antibody-drug conjugate, demonstrated potent antitumor activity against multiple tumors with favorable pharmacokinetics and safety profiles, displaying efficient cellular internalization, direct cytotoxicity, antibody-dependent cellular cytotoxicity, and bystander effects.	40499141
GIMR	2024-09-14	FL	4	CD274	Protein expression	Solid tumours; Head and neck squamous cell carcinoma; Non-small cell lung carcinoma	SGN-PDL1V	Phase 1. SGNPDL1V-001. NCT05208762. N=55. Single agent SGN-PDL1V showed ORR of 27% (13% confirmed) and median duration of confirmed responses of 7.9 months. Responses were seen across PD-L1 levels.	10.1016/j.annonc.2024.08.674
GIMR	2021-06-23	FL	4	CD274	Protein expression	Thymic carcinoma	Pembrolizumab	Phase 2. High PD-L1 expression is significantly correlating to responders in post hoc analysis. PD-L1 was positive if TPS >= 50%. Median PFS was longer in PD-L1 High group 24 v 9 months (PD-L1 low group).	29395863
GIMR	2025-06-29	FL	4	CD274	Protein expression	Urothelial carcinoma	Pembrolizumab + Cisplatin + Gemcitabine; Pembrolizumab + Carboplatin + Gemcitabine	Phase 3 KEYNOTE-361 trial. NCT02853305. N=993. Primary endpoints of PFS (HR 0.78, P=0.0033) and OS (HR 0.86, P=0.0407) were not met for pembrolizumab plus chemotherapy versus chemotherapy. TMB as a continuous variable was significantly associated with improved ORR, PFS, and OS in pembrolizumab monotherapy (one-sided P<0.001, P<0.001, P=0.007), with highest benefits observed in patients with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 versus chemotherapy alone. Cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1) were prespecified.	39475359
GIMR	2021-11-25	FL	4	CD276	Protein expression	Prostate cancer	MGC018	NCT03729596. Phase 1 expansion cohort studying MGC018 in B7-H3-expressing tumors. One partial radiological response observed, and 11 of 22 PSA response was seen in metastatic castrate-resistant prostate cancers.	10.1016/j.annonc.2021.08.1133
GIMR	2025-06-12	FL	4	CD276	Protein expression	Solid tumours	DB-1419	Preclinical study. DB-1419, a bifunctional B7-H3xPD-L1 antibody-drug conjugate, demonstrated potent antitumor activity against multiple tumors with favorable pharmacokinetics and safety profiles, displaying efficient cellular internalization, direct cytotoxicity, antibody-dependent cellular cytotoxicity, and bystander effects.	40499141
GIMR	2025-06-12	FL	4	CD276	Protein expression	Solid tumours	IBI3001	Preclinical study. IBI3001, a B7-H3/EGFR bispecific ADC, demonstrated potent cytotoxicity in cancer cells with varying B7-H3 and EGFR expression across multiple solid tumors, and showed robust tumor growth inhibition in xenograft models. Note cytotoxicties were demonstrated across all expression levels.	10.1158/1538-7445.AM2024-LB055
GIMR	2021-11-25	FL	4	CD276	Protein expression	Solid tumours	MGC018	NCT03729596. Phase 1 dose escalation study of MGC018.	10.1200/JCO.2021.39.15_suppl.2631
GIMR	2025-10-19	FL	4	CD44	Protein expression	Solid tumours	AMT-116	Phase 1/2 trials (NCT05725291; NCT06782334) of AMT-116, an anti-CD44v9 antibody-drug conjugate, showed manageable safety profile and promising antitumor activity across various solid tumors, with an ORR of 30% in EGFR wild-type NSCLC patients.	ESMO25.922MO
GIMR	2026-03-04	FL	4	CD46	Overexpression	Prostate cancer	FOR46	Phase I. FOR46 (FG-3246). NCT03575819. N=56. In patients with progressive mCRPC after ≥one androgen signaling inhibitors, median radiographic PFS was 8.7 months in efficacy evaluable subset (n=40). Confirmed ORR was 20% (5/25 RECIST-evaluable). PSA50 response was 36% (14/39). Median DOR was 7.5 months. Responders associated with higher on-treatment circulating effector CD8+ T cells. Note, Response was not clearly associated with CD46 expression despite mechanism of action.	40138611
GIMR	2021-03-10	FL	4	CDH1	Loss-of-function mutations	Breast cancer	Crizotinib; Foretinib	ROS1 inhibitors create synthetic lethality in CDH1 deficient breast cancer cell lines.	29610289
GIMR	2022-06-08	FL	4	CDH6	Protein expression	Renal cell carcinoma; Ovarian cancer	DS-6000a	NCT04707248. Phase 1 first-in-human evaluation of DS-6000a. 6 of 20 responder were seen across dosing levels. CDH is overexpressed in renal cell carcinoma and ovarian carcinoma. Cut-off to be determined.	10.1200/JCO.2022.40.16_suppl.3002
SuboKB	2020-04-16	FL	4	CDK12	Loss of protein expression	Ovarian cancer	Cisplatin; Veliparib	Preclinical study. Ovarian cancer-associated CDK12 mutations impair its catalytic activity, disrupt homologous recombination repair, and sensitize cells to cisplatin and PARP inhibitors by reducing BRCA1 levels.	24554720
GIMR	2020-04-16	FL	4	CDK12	Loss of protein expression	Prostate cancer	Anti-PD-1 monoclonal antibody	Integrative genomic analysis of 360 metastatic castration-resistant prostate cancer samples. The subtype with biallelic loss of CDK12 is characterized by focal tandem duplications, increased gene fusions, and elevated neoantigen burden, potentially benefiting from immune checkpoint immunotherapy.	29906450
GIMR	2021-02-28	FL	4	CDK12	Loss-of-function mutations	Prostate cancer	Pembrolizumab; Atezolizumab; Nivolumab + Ipilimumab; Durvalumab + Tremelimumab	Retrospective study identified 19 patient received immune checkpoint inhibitor. PSA50 responses 11% with estimated 9-month PFS of 23%. PFS was higher in chemotherapy-naive population.	32671317
GIMR	2023-06-14	FL	4	CDK12	Oncogenic mutations	Prostate cancer	Camonsertib	Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations.	37277454
GIMR	2022-07-04	FL	4	CDK12	Oncogenic mutations	Solid tumours	Pembrolizumab; Durvalumab; Nivolumab; Nivolumab + Ipilimumab	Retrospective series. 6 of 10 received immune checkpoint inhibitor experienced objective response.	34898046
GIMR	2022-05-25	FL	4	CDK12	Oncogenic mutations, Loss-of-function mutations	Prostate cancer	Pembrolizumab; Nivolumab	Retrospective study. In CDK12 altered metastatic castrate-resistance prostate cancer, 3 of 9 (ORR 33%) exposed to PD-1 inhibitors were associated with PSA response. Two of 9 had objective response to anti-PD-1 monotherapy.	32462107
SuboKB	2020-04-25	FL	4	CDK12	Protein expression	Triple-negative breast cancer	SR-4835	Preclinical study. SR-4835, a dual CDK12/CDK13 inhibitor, disables triple-negative breast cancer cells by triggering intronic polyadenylation site cleavage, suppressing DNA damage response proteins, and promoting synergy with DNA-damaging chemotherapy and PARP inhibitors.	31668947
GIMR	2022-07-08	FL	4	CDK12	Rearrangement	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2025-07-09	FL	4	CDK12	Truncating mutations, Kinase domain mutations	Prostate cancer	Rucaparib; Olaparib; Talazoparib	CRISPR/Cas9 models and the TRITON2 trial (N=11) demonstrate that CDK12-deficient prostate cancer cells are more sensitive to PARPi, with biallelic truncation mutants showing higher sensitivity (55% PSA reduction) than kinase domain mutants. In TRITON2, 6 of 11 patients responded, with 4/6 achieving stable disease and 2/6 progressive disease by RECIST. Response to rucaparib monotherapy varied by CDK12 mutation type and zygosity (monoallelic, gene arrangements, biallelic).	39321214
GIMR	2025-08-31	FL	4	CDK4	Amplification	Leydig cell tumour	Abemaciclib	Case report. Targeting CDK4 amplifications in metastatic Leydig cell tumor with abemaciclib showed significant tumor shrinkage (RECIST-equivalent partial response) with no major adverse events.	40825166
GIMR	2021-03-17	FL	4	CDK4	Amplification	Solid tumours	Palbociclib + Avelumab		ACTRN12620000568910
SuboKB	2020-04-16	FL	4	CDK4	Amplification and NOT overexpression	Rhabdomyosarcoma	Ribociclib	In PAX7-FOXO1 fusion-positive cell line	25810375
SuboKB	2020-04-23	FL	4	CDKN2A	Loss of protein expression	Glioblastoma	Palbociclib	Preclinical study. GBM cell lines and tumors. Co-deletion of CDKN2A predicts sensitivity to CDK4/6 inhibition, identifying a subset of GBMs likely to respond to targeted therapy.	20534551
SuboKB	2020-04-23	FL	4	CDKN2A	Loss of protein expression	Non-small cell lung cancer	Abemaciclib; Palbociclib	Phase 2 clinical trial and preclinical study. Palbociclib showed stable disease in 50% of p16-null NSCLC patients with median OS of 16.6 months, and preclinical data showed synergy with mTOR inhibition, particularly in tumors carrying RAS mutations.	27217383, 30647837
GIMR	2020-04-23	FL	4	CDKN2A	Loss-of-function mutations	Pancreatic adenocarcinoma	Palbociclib	Cell line study	25156567
SuboKB	2020-04-25	FL	4	CDKN2A	Oncogenic mutations	Non-small cell lung cancer	Palbociclib	Phase 2 TAPUR study. NCT02693535. N=28 (NSCLC with CDKN2A loss or mutation). Palbociclib monotherapy showed anti-tumor activity with a ORR of 3.6% and disease control rate of 29% (1 PR, 6 SD at 16 weeks), median PFS 7.9 weeks, and median OS 20.6 weeks.	10.1200/JCO.2019.37.15_suppl.9041
GIMR	2021-03-17	FL	4	CDKN2A	Oncogenic mutations, Deletions, Truncating mutations, Loss-of-function mutations	Solid tumours	Palbociclib + Avelumab		ACTRN12620000568910
POTTR	2020-04-16	FL	4	CDKN2A+MTAP	CDKN2A:deletion and MTAP:deletion	Solid tumours	EPZ015666	Preclinical study. MTAP-deficient cancer cells, frequently resulting from CDKN2A deletion, accumulate MTA, inhibiting PRMT5, and rendering them dependent on PRMT5, suggesting PRMT5 inhibitors as a potential therapy for MTAP/CDKN2A-deleted tumors.	26912361, 27068473
GIMR	2020-06-13	FL	4	CEACAM5	Overexpression	Non-small cell lung cancer	Tusamitamab ravtansine	Phase1/2 trial. NCT02187848. SAR408701, an antibody-drug conjugate, showed  antitumor activity in heavily pretreated NSQ NSCLC patients with high CEACAM5 expression, with an ORR of 20%.	10.1200/JCO.2020.38.15_suppl.9505
GIMR	2024-06-02	FL	4	CEACAM5	Protein expression	Colorectal cancer	M94140	Phase 1 trial. NCT05464030. N=40. M9140 demonstrated activity with manageable safety profile with ORR of  10% (4 PR) and median PFS of 6.7 months in heavily pretreated CRC patients. Note CEACAM5 expression is not required for enrollment into the trial.	10.1200/JCO.2024.42.16_suppl.3000
GIMR	2025-06-29	FL	4	CEACAM5	Protein expression	Solid tumours	BG-C477	Preclinical study. BG-C477, a CEACAM5-targeting ADC with topoisomerase 1 inhibitor payload, demonstrates cytotoxicity and antitumor efficacy in various CEACAM5-expressing cancer models. First-in-human trial ongoing (NCT06596473).	10.1158/1538-7445.AM2025-5461
GIMR	2022-06-24	FL	4	CEACAM5	Protein expression	Solid tumours	Tusamitamab ravtansine	Phase 1 Dose escalation study. In 31 patients, 3 objective responses were seen in 100-120 mg/m^2 dose levels. CEACAM5 expression level was 2+ in two responders of colorectal cancer. One gastric cancer.	35026412
SuboKB	2020-04-25	FL	4	CHEK1	Loss-of-function mutations	Prostate cancer	Olaparib	TOPARP-B	31806540
GIMR	2020-06-29	FL	4	CHEK1	Loss-of-function mutations	Solid tumours	VE-821	ATR/ATM inhibitor. Synthetic lethal with CHK1 inhibition	26748709
GIMR	2021-03-16	FL	4	CHEK1	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. Responder in Full eligible population	33583720
GIMR	2020-05-05	FL	4	CHEK1	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 1 patient only.	32343890
SuboKB	2020-04-16	FL	4	CHEK1	Overexpression	Small-cell lung cancer	Berzosertib + PF-477736	Preclinical study. Significant overexpression of CHEK1 and CDC25A/B/C genes in SCLC. ATR and CHK1 inhibitors induce genotoxic damage and apoptosis in SCLC cell lines, but not in lung adenocarcinoma cells, indicating SCLC's dependence on ATR/CHK1-mediated cell cycle checkpoints.	29138515
GIMR	2020-05-05	FL	4	CHEK2	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 12 patients. HR: 0.87 not powered.	32343890
SuboKB	2020-04-25	FL	4	CHEK2	Oncogenic mutations	Prostate cancer	Olaparib	TOPARP-B; single case of PSA50 response but no RECIST response.	31806540
GIMR	2024-07-15	FL	4	CLDN18	Overexpression, Protein expression, Low protein expression	Pancreatic adenocarcinoma	FG-M108 + Nab-paclitaxel + Gemcitabine	Phase 1b study. NCT04894825. Activities were observed in PDAC patients with positive Claudin 18.2 expression receiving FG-M108 + nab-paclitaxel and gemcitabine in CLDN18.2 expression. Immunohistochemistry (IHC) showed at least 1+ in at least 10% of cells.	10.1200/JCO.2024.42.16_suppl.4049
GIMR	2025-07-09	FL	4	CLDN18	Protein expression	Gastric cancer; Pancreatic adenocarcinoma; Oesophageal cancer	AZD6422	Preclinical study. AZD6422. NCT05981235. Armored CAR-T targeting CLDN18.2 with TGF-beta resistance and optimized manufacturing showed antitumor activity in patient-derived xenograft models of gastric, pancreatic, and esophageal cancers with varying CLDN18.2 and TGF-beta  levels.	39321207
GIMR	2022-06-04	FL	4	CLDN18	Protein expression	Solid tumours	MIL93	Phase 1. NCT04671875. In 10 evaluable patients, 1 responders were seen in CLDN18.2-positive gastric cancer achieved PR.	10.1200/JCO.2022.40.16_suppl.3086
GIMR	2025-06-01	FL	4	CLDN6	Protein expression	Ovarian cancer; Solid tumours	BNT142	Phase 1/2 BNT142-01 trial. NCT05262530. N=65. BNT142 showed  anti-tumor activity with 7 partial responses in ovarian cancer and a disease control rate of 58% across all dose levels in CLDN6+ advanced solid tumors. CLDN6 positivity is defined as ≥ membrane positivity in 10% of cell. No clear relationship beween CLDN6 expression level versus response seen.	10.1200/JCO.2025.43.16_suppl.2501
GIMR	2024-09-15	FL	4	CLDN6	Protein expression	Solid tumours; Testicular cancer; Gastric cancer; Non-small cell lung cancer	DS-9606a	Phase 1. NCT05394675. N=40. In Phase 1 DS-9606a trial, confirmed responses were seen in in germ-cell tumours, gastric cancer, and non-small cell lung cancer. CLDN6 expression is not required as part of the eligibiity for entry.	10.1016/j.annonc.2024.08.677
GIMR	2024-09-15	FL	4	CLDN6	Protein expression	Solid tumours; Testicular cancer; Ovarian cancer	BNT211	Phase 1. BNT211-01 trial. NCT04503278. N=59. Updated results showed ORR of 38% and DCR of 69%. TRAE in 88% of patients, 64% Grade 3 or more with 39% SAE.	10.1016/j.annonc.2024.08.678
GIMR	2021-03-21	FL	4	Consensus molecular subtype	CMS2, CMS3	Colorectal adenocarcinoma	Capecitabine + Bevacizumab	MAX: Exploratory analysis showed CMS2 and CMS3 is associated with longer PFS in bevacizumab groups, but not OS.	30247524
GIMR	2021-03-21	FL	4	Consensus molecular subtype	CMS4	Colorectal adenocarcinoma	FOLFIRI + Cetuximab	FIRE-3: for RAS wild-type tumours, CMS4 was associated with longer PFS (HR 0.67, p=0.048) and OS (HR 0.57, p=0.008) in Cetuximab versus Bevacizumab in combination with FOLFIRI in the first-line setting.	31868905
GIMR	2023-05-29	FL	4	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	AMB-05X	Phase 2 trial. N=8. Intra-articular administration of AMB-05X, a CSF1R antibody, yielded high and sustained local concentrations with low systemic exposures, resulting in significant pharmacodynamic effects in tenosynovial giant cell tumor patients.	10.1016/j.annonc.2022.07.1589
GIMR	2021-12-29	FL	4	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Imatinib	Case report. Complete response to Imatinib.	18296418
GIMR	2021-12-29	FL	4	CSF1	Overexpression, Fusion, Rearrangement	Tenosynovial giant cell tumor	Imatinib	Retrospective study. ORR 19% (5/27) had RECIST-assessed responses, with 1 complete response and 4 partial responses. 20 (74%) had SD. Alteration in CSF1 signalling is implied in the neoplastic development of TCGT, but the therapeutic eligibility is not selected by CSF1.	21823110
GIMR	2020-07-02	FL	4	CXCL13	Overexpression	Urothelial carcinoma	Nivolumab; Atezolizumab	Retrospective biomarker study	32554706
GIMR	2025-02-24	FL	4	DAXX	Oncogenic mutation	Solid tumours	Tuvusertib	Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2.	38407317
GIMR	2022-04-19	FL	4	DAXX	Overexpression	Triple-negative breast cancer	Veliparib	Cell line study. Increased sensitivity to PARP1/2 inhibitor (veliparib) was observed in BRCA-Proficient triple-negative breast cancer cell-line with DAXX overexpression.	31029033
GIMR	2025-04-23	FL	4	DLK1	Protein expression	Neuroblastoma	ADCT-701	Preclinical study. DLK1 is an immunotherapeutic target in neuroblastoma, characterized by high expression linked to super-enhancer activation. ADCT-701 antibody-drug conjugate demonstrating potent cytotoxicity in xenograft models.	39454577
GIMR	2023-01-25	FL	4	DNMT3A	Loss-of-function mutations	Non-small cell lung cancer	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody		10.1200/JCO.2021.39.15_suppl.9113
GIMR	2025-02-17	FL	4	DNMT3A	Oncogenic mutations, Deletions, Truncating mutations, Loss-of-function mutations	Non-small cell lung cancer	SP2509	Preclinical study. KDM1A is a synthetic lethal partner of DNMT3A deletion in non-small cell lung cancer, reducing viability of DNMT3A-deficient cells through apoptosis.	38951697
GIMR	2021-05-31	FL	4	EGFR	A289V	Glioblastoma	Osimertinib	Case report of complete response of left frontal lobe tumor after 4 weeks of osimertinib.	31769726
GIMR	2021-12-29	FL	4	EGFR	A763insFQEA, V769insASV, D770insSVD, H773insNPH	Non-small cell lung cancer	Tarloxotinib	Preclinical study. Tarloxotinib-E showed efficacy against Ba/F3 cells with various EGFR exon 20 mutations, with identified acquired resistance mechanisms being T790M or C797S secondary mutations depending on the original EGFR exon 20 mutation.	33710795
GIMR	2020-06-11	FL	4	EGFR	Amplification	Cervical cancer	Afatinib	Case report. A 52-year-old patient with EGFR-amplified metastatic cervical squamous cell carcinoma benefited from afatinib with a PFS of 5.5 months and achieved partial response, and subsequently achieved stable disease with everolimus and afatinib at disease progression.	32184619
GIMR	2022-04-09	FL	4	EGFR	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma	Cetuximab; ABT-806; Panitumumab; Gefitinib; Erlotinib	Large international retrospective study (N=60). EGFR-amplified GEA received EGFRi, including 31 with concurrent chemotherapy. ORR was 43% and median PFS was 4.6 months across all lines. OS: 20.6 months (first-line), 9 months (second-line), and 8.4 months (third-line) exceeding historical real-world control of 11.2-month.	35349370
GIMR	2020-04-16	FL	4	EGFR	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma	FOLFOX + ABT-806; FOLFIRI + Cetuximab; Cetuximab	Four of 7 patients with high-level amplification with three complete responses. Minimum EGFR copy number in tissue was 54.	29449271
GIMR	2020-06-11	FL	4	EGFR	Amplification	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Cetuximab	Phase 2 study (N=7) of anti-EGFR treatment in EGFR-amplified gastroesophageal adenocarcinoma patients demonstrated ORR of 58% (including 1 CR), DCR of 100%, and median PFS of 10 months. Resistance mechanisms were identified through NGS and ctDNA analysis.	29449271
GIMR	2021-05-11	FL	4	EGFR	Amplification	Glioblastoma	Carboxyamidotriazole Orotate + Temozolomide	Exploratory analysis from the phase 1 study showed high rate of responses in EGFR-amplified tumors	29683790
GIMR	2021-09-26	FL	4	EGFR	Amplification	Non-small cell lung cancer	Afatinib	Phase 2 EGFR FISH-positive NSCLC. ORR 13%. DCR 51%.	25514804
GIMR	2020-06-11	FL	4	EGFR	Amplification	Penile cancer	Dacomitinib	Post hoc subgroup analysis: 2/4 patients responded	28921872
GIMR	2020-07-03	FL	4	EGFR	Amplification	Triple-negative breast cancer	Cetuximab	Case report. A patient with EGFR-amplified heavily pretreated metastatic triple-negative breast cancer experienced a dramatic response to cetuximab as 7th-line treatment, with disease progression occurring 8 months after treatment initiation, and molecular analysis suggested loss of EGFR phosphorylation and acquisition of an NF1 mutation as potential resistance mechanisms.	35100682
GIMR	2021-05-11	FL	4	EGFR	Amplification AND G598V	Glioblastoma	Dacomitinib	Phase 2: Dacomitinib was not effecitive in EGFR-amplified GBM (5/30 patients in arm B achieved PFS6 and did not meet the primary endpoint).	10.1200/PO.19.00295
GIMR	2020-06-11	FL	4	EGFR	Amplification AND L858R; Amplification AND Exon 19 deletion	Non-small cell lung cancer	Erlotinib	Retrospective study showing the subgroup with EGFR amplification and sensitizing mutations had prolonged PFS and ORR than those without. 	30284706
GIMR	2021-09-26	FL	4	EGFR	Amplification and NOT Oncogenic mutation	Non-small cell lung cancer	Afatinib	Phase 2 EGFR FISH-positive NSCLC. Responders were seen with an ORR 4/43 (9%) in EGFR wild-type amplified patients. PFS 7.9 weeks.	25514804
GIMR	2021-09-26	FL	4	EGFR	Amplification and NOT Oncogenic mutation	Non-small cell lung cancer	Gefitinib	Case report. Lung adenocarcinoma, wild-type EGFR, and EGFR gene amplification showed complete remission after treatment with gefitinib, suggesting EGFR gene amplification as a potential biomarker for predicting response to EGFR-TKIs in patients with advanced NSCLC.	30622811
GIMR	2021-09-26	FL	4	EGFR	Amplification and NOT Oncogenic mutation	Non-small cell lung cancer	Gefitinib; Erlotinib	Retrospective study in 502 patients. In 226 patients with EGFR wildtype with amplification (FISH positive) treated with first-generation EGFR TKIs, ORR was 18% (11/62) versus 9% (16/185), and PFS was 4.4 months (FISH-positive) versus 2.0 months (FISH-negative). This is compared to mutation-positive group where ORR was 44% (110/252).	23557218
GIMR	2020-06-11	FL	4	EGFR	Amplification AND NOT Oncogenic mutations	Non-small cell lung cancer	Afatinib	ORR of 4/43 (9%) in the EGFR FISH-positive subgroup (gene/chr ratio >= 2, or Copy number >= 15) without EGFR sensitising mutation. 	25514804
GIMR	2024-04-20	FL	4	EGFR	Amplification, vIII	Glioblastoma	EO1001	Preclinical study. NT113, a pan-ERBB inhibitor with high brain penetrance, showing activity in glioblastoma xenografts model with EGFR amplification and models transfected with vIII.	25313012
GIMr	2025-05-24	FL	4	EGFR	C797S and T790M 	Non-small cell lung cancer	Osimertinib + Gefitinib	Case report. Combination osimertinib and gefitinib in a NSCLC patient with EGFR C797S and T790M mutations in trans demonstrated brief clinical improvement with rapid decline in C797S mutation subclone, but the patient ultimately died from progressive disease 6 weeks after starting therapy.	28843359
GIMR	2021-07-12	FL/MI	4	EGFR	E709_T710delinsD	Non-small cell lung cancer	Afatinib	Case report. A lung adenocarcinoma patient with rare EGFR E709_T710delinsD mutation achieved 23 months progression-free survival when treated with afatinib as first-line therapy, and subsequent almonertinib treatment resulted in stable disease.	34178699
GIMR	2021-07-12	FL/MI	4	EGFR	E709_T710delinsD	Non-small cell lung cancer	Afatinib	Case report. Stage IV lung adenocarcinoma harboring the rare EGFR exon 18 E709_T710delinsD mutation showed significant clinical and radiographic response to treatment with afatinib.	28625646
GIMR	2021-07-12	FL/MI	4	EGFR	E709_T710delinsD	Non-small cell lung cancer	Gefitinib	Case report. Stage IV NSCLC harboring the rare EGFR delE709_T710insD mutation achieved a partial response to erlotinib, with a 47% reduction in tumor size.	22982663
GIMR	2021-09-17	FL	4	EGFR	EGFR-RAD51 fusion	Non-small cell lung cancer	Erlotinib	Preclinical and case series study. EGFR gene fusions, most commonly EGFR-RAD51, were identified in lung cancer and found to be oncogenic and targetable with EGFR tyrosine kinase inhibitors (TKI) and therapeutic antibodies, with documented antitumor responses in four patients treated with EGFR TKI.	27102076
GIMR	2020-05-20	FL	4	EGFR	EGFR-RAD51 Fusion, EGFR-PURB fusion	Non-small cell lung cancer	Erlotinib	Case report. Stage IV NSCLC harbouring EGFR-RAD51 fusion experienced a remarkable tumour response to erlotinib, suggesting that NSCLC patients with EGFR-RAD51 fusion may respond to treatment with EGFR inhibitors.	29290255, 27413714
GIMR	2020-09-03	FL	4	EGFR	EGFR-SEPT14 Fusion	Colorectal adenocarcinoma	Erlotinib	Case report. Colorectal adenocarcinoma harboring a rare EGFR-SEPT14 fusion achieved a partial response to erlotinib, an EGFR tyrosine kinase inhibitor, before developing resistance with the emergence of EGFRvIII mutation.	32162810
GIMR	2023-04-05	FL	4	EGFR	EGFR-SEPT14 Fusion	Non-small cell lung cancer	Osimertinib + Pemetrexed	Case report of a NSCLC leptomeningeal metastasis harbouring EGFR-SEPT14 osimertinib with intrathecal pemetrexed.	34486539
GIMR	2020-06-11	FL	4	EGFR	Exon 18 deletion, Exon 18 mutation, E709_T710delinsD, E709K, G719A	Non-small cell lung cancer	Erlotinib; Gefitinib; Afatinib; Osimertinib	Preclinical study. Lung cancer cells with EGFR exon 18 mutations (G719A, E709K, Del18) showed higher sensitivity to afatinib and neratinib compared to 1st and 3rd generation TKIs, indicating potential effective treatment options for patients with these mutations.	26206867
GIMR	2020-10-05	FL	4	EGFR	Exon 19 deletion and amplification; L858R and amplification; Exon 21 mutation  and amplification	Non-small cell lung cancer	Osimertinib + Necitumumab	ORCHARD trial	NCT03944772, NCT02496663
GIMR	2021-12-29	FL	4	EGFR	Exon 19 deletion and L718V, Exon 19 deletion and G724S, Exon 19 deletion and L792F, Exon 19 deletion and L792H, Exon 19 deletion and C797S, L858R and L718Q, L858R and L718V, L858R and L792F, L858R and L792H, L858R and C797G	Non-small cell lung cancer	Tarloxotinib	Preclinical study. Tarloxotinib-E showed activity against Ba/F3 cells with various EGFR exon 20 mutations, with identified acquired resistance mechanisms being T790M or C797S secondary mutations, influenced by the original EGFR exon 20 mutation.	33710795
GIMR	2021-12-29	FL	4	EGFR	Exon 19 deletion and L718V, Exon 19 deletion and G724S, Exon 19 deletion and L792F, Exon 19 deletion and L792H, Exon 19 deletion and C797S, L858R and L718Q, L858R and L718V, L858R and L792F, L858R and L792H, L858R and C797G, L858R and C797S 	Non-small cell lung cancer	Afatinib	Preclinical study. Afatinib showed activities against Ba/F3 cells with various EGFR exon 20 mutations	33710795
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and C797S, Exon 19 deletion and L718V, E709K and L858R, E709A, S720P, G724S, T725M, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and C797S, L858R and G724S, L861R, L861Q	Non-small cell lung cancer	Gefitinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and C797S, Exon 19 deletion and L718V, E709K and L858R, E709K and G719S, E709A and G719S, E709A, E709K, G719S, G719A, G719A and L861Q, G719A and R776C, S720P, T725M, I740dupIPVAK, L747S, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, R776H, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q	Non-small cell lung cancer	Erlotinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709K and G719S, E709A and G719S, E709A, E709K, G719S, G719A, G719A and L861Q, G719A and R776C, G719S and T790M, S720P, T725M, I740dupIPVAK, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and V769L, V769L, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L792H, L858R and G724S, L861R, L861Q	Non-small cell lung cancer	Neratinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q, L718V, G719S, G719A, G719A and L861Q, G719A and R776C, G719A and T790M, G719S and T790M, S720P, G724S, T725M, I740dupIPVAK, L747P, L747S, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, A767insASV, S768dupSVD, S768dupSVD and V769M, S768I and V769L, S768I and V774M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, V774M, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q	Non-small cell lung cancer	Poziotinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q, L718V, G719S, G719A, G719A and L861Q, G719A and R776C, S720P, G724S, T725M, I740dupIPVAK, L747P, L747S, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and V769L, S768I and V774M, V769L, V774M, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q	Non-small cell lung cancer	Afatinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T854I, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q, L718V, G719S, G719A, G719A and L861Q, G719A and R776C, S720P, G724S, T725M, I740dupIPVAK, L747P, L747S, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and V769L, S768I and V774M, V769L, V774M, R776H, R776C, S784F, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and C797S, L858R and G724S, L861R, L861Q	Non-small cell lung cancer	Dacomitinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, E709K and L858R, E709A and G719S, E709A, E709K, G719A and L861Q, G719A and R776C, G719A and T790M, S720P, G724S and T790M, T725M, L747S, L747_K754delInsATSPE, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I, S768I and V774M, S768I and T790M, V774M, R776H, S784F, T790M, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L792H, L861R, L861Q	Non-small cell lung cancer	Osimertinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and L792H, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L718V, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, G719S, G719A, G719A and R776C, G719A and T790M, G719S and T790M, S720P, T725M, I740dupIPVAK, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768I and T790M, S784F, T790M, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718V, L858R and T790M and L792H, L861R, L861Q	Non-small cell lung cancer	Lazertinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and L792H, Exon 19 deletion and L718V, Exon 19 deletion and L718Q, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L718V, E709K and L858R, E709_T710delInsD, E709K and G719S, E709A and G719S, E709A, E709K, L718Q and T790M, G719S, G719A, G719A and L861Q, G719A and R776C, G719A and T790M, G719S and T790M, S720P, G724S and T790M, T725M, I740dupIPVAK, L747P, L747S, L747_K754delInsATSPE, K754E, K757R, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768dupSVD, S768dupSVD and V769M, S768I, S768I and V769L, S768I and V774M, S768I and T790M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, V774M, R776H, R776C, S784F, T790M, S811F, L833F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L792H, L861R, L861Q	Non-small cell lung cancer	Nazartinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	4	EGFR	Exon 19 deletion, Exon 19 deletion and T790M, E709K and L858R, E709_T710delInsD, G719A and T790M, S720P, K754E, D761N, A763_Y764insFQEA, A763_Y764insLQEA, S768dupSVD, S768dupSVD and V769M, S768I and V769L, H773insNPH, R776C, S784F, S811F, L833V, L858R and V834L, L858R, L858R and S784F, L858R and L792H, L858R and G724S, L861R	Non-small cell lung cancer	Mobocertinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios < 0.25 after drug exposure are listed.	34526717
GIMR	2024-09-30	FL	4	EGFR	Exon 19 deletion, L858R	Non-small cell lung cancer	Erlotinib; Gefitinib		33632773
GIMR	2025-03-16	FL	4	EGFR	Exon 19 deletion, L858R, Exon 21 mutation	Non-small cell lung cancer	AZD9592	Preclinical study. EGFR-cMET bispecific ADC showed antitumour activities in NSCLC and head and neck squamous cell carcinoma PDX models, with responses observed across a range of dose levels. Note activities are seen in with or without EGFR mutations in NSCLC as well as in head and neck squamous cell carcinoma.	10.1158/1538-7445.AM2023-5736
GIMR	2024-09-30	FL	4	EGFR	Exon 19 deletion, L858R, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA	Non-small cell lung cancer	Afatinib	Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR.	33632773
GIMR	2024-09-30	FL	4	EGFR	Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup	Non-small cell lung cancer	Osimertinib	Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR.	33632773
GIMR	2024-09-30	FL	4	EGFR	Exon 19 deletion, L858R, L861R, L861Q, A763_Y764insFQEA, P772_H773insGNP, A767_V769dup, T790M, G719A, G719S, S768I, Exon 20 insertion, N771_H773dup, S768_D770dup	Non-small cell lung cancer	Mobocertinib	Preclinical study. Mobocertinib (TAK-788) demonstrated potent inhibition of EGFR exon 20 insertion mutants in non-small cell lung cancer with selectivity over wild-type EGFR.	33632773
GIMR	2025-06-04	FL	4	EGFR	Exon 20 insertions, C797S	Non-small cell lung cancer	Sevabertinib	Phase 1. NCT05099172. BAY2927088 is an oral TKI targeting EGFR and HER2 mutations that demonstrates strong potency and high selectivity for mutant versus wild-type EGFR, showing activities in NSCLC patients with EGFR exon 20 insertion mutations and EGFR C797S acquired resistance mutation.	10.1158/1538-7445.AM2023-CT126
POTTR	2020-04-16	FL	4	EGFR	Exon 20 mutation	Non-small cell lung cancer	EGFR inhibitor,exon 20 selective   	Review article	30854234
GIMR	2023-12-19	FL	4	EGFR	G63R, E114K, R165Q, R222C, S492R, P596L, K708R, E709K, G719S, G724S, L858R	Colorectal cancer	Cetuximab; Panitumumab	Preclinical study. Somatic EGFR mutations in colon cancer were identified by systematic functional screening and demonstrated to be oncogenic, ligand-independent and transform cells in vitro and responsive to cetuximab or panitumumab both in vitro and in vivo.	31290142
GIMR	2021-06-01	FL	4	EGFR	G719, S768I, L861Q	Non-small cell lung cancer	Osimertinib	Patient-derived xenografts (PDX) and cell lines studies	32943544
GIMR	2022-02-23	FL	4	EGFR	G724S and R776H	Non-small cell lung cancer	Afatinib	Case report. A novel KIF5B-EGFR fusion identified in lung adenocarcinoma demonstrated remarkable response to Afatinib treatment.	33644199
GIMR	2021-10-02	FL	4	EGFR	I740_K745dupIPVAIK	Non-small cell lung cancer	Osimertinib	Two case reports showing respnses to Osimertinib in metastatic NSCLC harbouring this exon 19 duplication.	32216945
GIMR	2021-09-17	FL	4	EGFR	KIF5B-EGFR fusion	Non-small cell lung cancer	Afatinib + Bevacizumab	Case report. A novel KIF5B-EGFR fusion was identified in lung adenocarcinoma, and the patient showed a response to EGFR tyrosine kinase inhibitors (TKIs).	32903808
GIMR	2021-12-06	FL	4	EGFR	Kinase domain duplication	Non-small cell lung cancer	Afatinib	Case report. Afatinib achieved disease control in a Chinese patient with lung adenocarcinoma harboring rare EGFR exon 18-25 kinase domain duplication.	31567148
GIMR	2020-06-11	FL	4	EGFR	Kinase domain duplication	Non-small cell lung cancer	Afatinib; Erlotinib; Gefitinib	EGFR kinase domain duplication (EGFR-KDD) is a rare oncogenic driver in NSCLC, identified in 0.12% of patients, with 85% having the canonical exon 18-25 duplication, and shows partial response to targeted therapies, notably afatinib, in some patients.	30255937, 19915609, 26286086
GIMR	2021-12-06	FL	4	EGFR	Kinase domain duplication	Non-small cell lung cancer	Erlotinib; Osimertinib	Case report showing response to both erlotinib and osimertinib (4 and 15 months respectively) in a patient with carcinomatous meningitis. Duplication of intron 17-25 was detected by Sanger sequencing. 	34240806
GIMR	2021-12-06	FL	4	EGFR	Kinase domain duplication	Non-small cell lung cancer	Gefitinib	Case report of tandem duplication of exons 18-25 responding to Gefitinib with durable response.	26398831
GIMR	2021-12-06	FL	4	EGFR	Kinase domain duplication	Non-small cell lung cancer	Icotinib; Osimertinib	Case report. Response to Icotinib and second line osimertinib. Duration of response 21 months. 	33392076
GIMR	2021-12-06	FL	4	EGFR	Kinase domain duplication	Non-small cell lung cancer	Osimertinib	Case reports. Two NSCLC patients with EGFR kinase domain duplication (KDD) mutation, one of whom achieved stable disease with osimertinib after resistance to afatinib, highlighting osimertinib as a potential effective therapy following resistance to first- and second-generation EGFR-TKIs.	34261918
GIMR	2021-12-06	FL	4	EGFR	Kinase domain duplication AND T790M	Non-small cell lung cancer	Osimertinib; Lazertinib 	Cell line study. EGFR-KDDT790M Ba/F3 cell line. T790M-positive cell lines were sensitive to 3rd generation TKIs	33940786
GIMR	2020-04-16	FL	4	EGFR	L718V	Non-small cell lung cancer	Afatinib	Case report. Concomitant L858 and loss of T790M	29571986
GIMR	2021-03-31	FL	4	EGFR	L747_A750delinsP	Non-small cell lung cancer	Afatinib	Cell line and in silico structural study demonstrating increased sensitivity to afatinib over erlotinib and osimertinib.	31182434
GIMR	2021-09-29	FL	4	EGFR	L747_P753delinsS, L747_A750delinsP, Exon 19 indels	Non-small cell lung cancer	Gefitinib; Erlotinib	Retrospective series. ORR to first generation TKI: L747_P753delinsS (12/24, 50%), L747_A750delinsP (20/23, 87%).	33171317
GIMR	2020-06-08	FL	4	EGFR	L747P, L747S	Non-small cell lung cancer	Afatinib	Preclinical and clinical study. Afatinib showed improved PFS (11.97 months) and ORR (80%) in patients with lung adenocarcinoma harboring uncommon EGFR p.L747P and p.L747S mutations, with no patients acquiring p.T790M resistance after afatinib failure.	31200815
GIMR	2020-04-16	FL	4	EGFR	L747S, D761Y, T854A	Non-small cell lung cancer	Afatinib; Osimertinib	Preclinical study. Irreversible EGFR-TKIs showed efficacy against uncommon secondary resistant EGFR mutations L747S, D761Y, and T854A.	28424065
GIMR	2020-06-11	FL	4	EGFR	L833V, H835L	Non-small cell lung cancer	Gefitinib	Case report. A lung adenocarcinoma patient with a heterozygous complex mutation of L833V and H835L in the EGFR gene showed a good response to gefitinib treatment.	21422421
GIMR	2022-03-15	FL	4	EGFR	Oncogenic mutations	Non-small cell lung cancer	ABBV-637 + Osimertinib	Phase 1 dose escalation and expansion. NCT04721015. ABBV-637 plus osimertinib showed clinical activity with ORR of 14% and 10% in 3rd-line and 2nd-line therapy respectively, and a manageable safety profile in patients with relapsed/refractory EGFR-mutated NSCLC. Update 2025-05-27	10.1016/j.annonc.2023.09.2352
GIMR	2025-06-09	FL	4	EGFR	Oncogenic mutations	Non-small cell lung cancer	BC3195	Phase 1. NCT05957471, N=56, BC3195, an ADC targeting CDH3, showed preliminary activity in heavily pretreated patients with NSCLC, particularly in EGFR-mutant NSCLC with an ORR of 50% and mPFS > 6 months.	10.1200/JCO.2025.43.16_suppl.3019
GIMR	2021-02-12	FL	4	EGFR	Oncogenic mutations	Non-small cell lung cancer	Patritumab deruxtecan	Treatment-refractory EGFR mutant NSCLC. ORR 25% seen in multiple mechanisms of EGFR TKI resistance.	10.1016/j.annonc.2020.08.2295
GIMR	2023-06-23	FL	4	EGFR	Oncogenic mutations, Exon 20 insertion, C797S	Non-small cell lung cancer	GB263T	Cell line study.	10.1158/1538-7445.AM2022-LB538
GIMR	2020-06-28	FL	4	EGFR	Overexpression	Non-small cell lung cancer; Head and neck squamous cell carcinoma 	Serclutamab Talirine		10.1200/JCO.2020.38.15_suppl.TPS3649
GIMR	2023-07-19	FL	4	EGFR	Overexpression, Protein expression	Solid tumour	MVC-101	Preclinical study. In vitro and in vivo studies showed TAK-186 resulted in regressions of EGFR-expressing solid tumours.	35728872
GIMR	2025-06-12	FL	4	EGFR	Protein expression	Solid tumours	IBI3001	Preclinical study. IBI3001, a B7-H3/EGFR bispecific ADC, demonstrated potent cytotoxicity in cancer cells with varying B7-H3 and EGFR expression across multiple solid tumors, and showed robust tumor growth inhibition in xenograft models. Note cytotoxicties were demonstrated across all expression levels.	10.1158/1538-7445.AM2024-LB055
GIMR	2025-06-12	FL	4	EGFR	Protein expression	Solid tumours	IBI334	Preclinical study. IBI334, a novel ADCC-enhanced B7-H3/EGFR bispecific antibody, showed enhanced EGFR signal inhibition and potent efficacy in various xenograft models, with a large therapeutic window of >200 folds, indicating potential for safe and effective treatment of EGFR-driven solid tumors.	10.1158/1538-7445.AM2024-LB056
GIMR	2022-03-03	FL	4	EGFR	Protein expression, Overexpression	Pancreatic adenocarcinoma	E-EDV-D682	Interim data from Phase 1/2 ACTRN12619000385145. N=9. Confirmed response at 4 months in 4 of 5 patients. CBR 8 weeks 89%.	10.1200/JCO.2020.38.15_suppl.4632
GIMR	2022-02-23	FL	4	EGFR	R776H	Non-small cell lung cancer	Osimertinib	Retrospective study. 	10.1200/JCO.2021.39.15_suppl.e21001
GIMR	2022-02-23	FL	4	EGFR	R776H, L861Q, G719S and E709K, G719S and R776H, L747_T751del and D837T, L833V and H835L, L858R and G873E, L858R and A871E	Non-small cell lung cancer	Erlotinib; Gefitinib; Afatinib	Retrospective study demonstrating response seen in harbouring the following mutations to first- and- second generation EGFR TKIs.	27875527
GIMR	2021-11-10	FL	4	EGFR	T751_I759delinsS	Non-small cell lung cancer	Afatinib; Osimertinib	Case report. Lung adenocarcinoma patient with rare EGFR T751_I759delinsS mutation showed initial good response to afatinib and subsequent response to osimertinib after developing resistance to afatinib, highlighting potential treatment options for patients with rare EGFR mutations.	34729927
GIMR	2020-05-15	FL	4	EGFR	T790M and C797S and T790M-C797S trans-allelic conformation	Non-small cell lung cancer	Erlotinib + Osimertinib	Case report. Lung adenocarcinoma with EGFR 19Del/T790M/in trans-C797S mutations demonstrated durable clinical response to combined first- and third-generation EGFR tyrosine kinase inhibitor therapy.	31075545
GIMR	2023-07-31	FL	4	EGFR	V659E	Non-small cell lung cancer	Afatinib; Pyrotinib	Retrospective study. N=7812. Lung adenocarcinoma with ERBB2 V659E mutation. HER2 inhibitors resulted in longer median PFS compared to chemotherapy. Afatinib and pyrotinib showed stronger binding ability to the HER2 kinase domain.	10.1200/JCO.2020.38.15_suppl.e21521
GIMR	2025-07-30	FL	4	EGFR	vIII	Glioblastoma	CARv3-TEAM-E T cell	Phase 1. INCIPIENT. NCT05660369. N=3. CARv3-TEAM-E T cells (dual-targeting EGFRvIII and wild-type EGFR) induced rapid tumor regression (transient in 2/3) with no >grade 3 toxicity; one patient had durable response. Liquid biopsy detected EGFR copy number decline. Contrasts with prior single-antigen CAR T trials limited by tumor heterogeneity and antigen loss.	38477966
GIMR	2021-05-31	FL	4	EGFR	vIII	Glioblastoma	Osimertinib	Osimertinib inhibited an EGFR vIII glioblastoma cell line and associated xenograft models.	32547705
GIMR	2020-04-16	FL	4	EGFR	vIII	Glioma; Glioblastoma	AMG-596	Preclinical study. EGFRvIII-targeted bispecific T-cell engager shows therapeutic activity in glioblastoma by redirecting T cells to eliminate EGFRvIII-expressing GBM cells.	23927666, 10.1200/JCO.2019.37.15_suppl.TPS2071
GIMR	2020-04-16	FL	4	EGFR	vIII	Glioma; Glioblastoma	Depatuxizumab mafodotin	Phase 2. M12-356. NCT01800695. EGFR-amplified, recurrent glioblastoma. N=66. Depatuxizumab mafodotin resulted in ORR of 7% with 6-month PFS rate of 29%.	29075855
GIMR	2021-05-11	FL	4	EGFR	vIII AND D247Y	Glioblastoma	Afatinib + Temozolomide	Case report: prolonged response to afatinib with temozolomide in recurrent multifocal GBM	26423602
GIMR	2023-04-05	FL	4	EGFR	vIII, EGFR-SEPT14 fusion	Glioblastoma	Erlotinib; Lapatinib	Preclinical study. Integrated analysis of genomic alterations in glioblastoma revealed LZTR1 mutations with loss of heterozygosity, CTNND2 loss-of-function mutations associated with mesenchymal phenotype, and EGFR fusions (e.g., EGFR-SEPT14) that activate STAT3 signaling and confer sensitivity to EGFR inhibition.	23917401
GIMR	2021-05-11	FL	4	EGFR	vIII, T263P, A289D, A289V, G598V	Glioblastoma	Lapatinib	Cells with EGFR ectodomain mutation have increased sensitivity to lapatinib, but lapatinib did not achieve sufficient intratumoral concentrations in GBM patients. Response to lapatinib was not assessable	22588883
GIMR	2020-10-05	FL	4	EGFR+ALK	EGFR:Oncogenic mutations and ALK:fusion	Non-small cell lung cancer	Osimertinib + Crizotinib; Osimertinib + Alectinib	Two case reports	30957057
GIMR	2021-05-28	FL	4	EGFR+BRAF	EGFR:Oncogenic mutations and BRAF:V600E	Non-small cell lung cancer	Dabrafenib + Trametinib + Osimertinib	Case report. A patient with EGFR-mutant/BRAF V600E lung adenocarcinoma showed impressive radiological and ctDNA response to combination therapy with dabrafenib, trametinib, and osimertinib, suggesting potential efficacy in patients with acquired BRAF V600E resistance mutation.	33580193
GIMR	2022-09-07	FL	4	EGFR+ERBB2	EGFR:Exon 19 deletion and ERBB2:Amplification	Non-small cell lung cancer	Afatinib + Bevacizumab	Case report. Resistance to Gefitinib (Acquired) and Osimertinib associated with acquired ERBB2 amplification in a case of exon 19 deletion. Tumour shrinkage to ERBB2 was observed with overall SD of > 6 months following treatment with afatinib + bevacizumab.	33663050
GIMR	2022-09-07	FL	4	EGFR+ERBB2	EGFR:Exon 19 deletion and ERBB2:Amplification	Non-small cell lung cancer	Gefitinib; Osimertinib	Case report. Resistance to Gefitinib (Acquired) and Osimertinib associated with acquired ERBB2 amplification in a case of exon 19 deletion. Tumour shrinkage to ERBB2 was observed with overall SD of > 6 months following treatment with afatinib + bevacizumab.	33663050
GIMR	2020-11-17	FL	4	EGFR+ERRFI1	EGFR:low expression AND ERRFI1:Oncogenic mutations	Solid tumours	MK-2206 + Gemcitabine	Cell line study. ERRFI1 differentially regulates EGFR and AKT pathways in a context-dependent manner, promoting cell growth and chemotherapy desensitization in EGFR-low cells while inhibiting growth in EGFR-high cells. AKT inhibitors sensitize cells to chemotherapy.	29335246
GIMR	2020-11-17	FL	4	EGFR+ERRFI1	EGFR:overexpression AND ERRFI1:Oncogenic mutations	Solid tumours	Gefitinib + Gemcitabine	Cell line study of effect of EFFRI1. EGFR inhibition sensitises cell to chemotherapy	29335246
GIMR	2020-06-23	FL	4	EGFR+MET	EGFR:Oncogenic mutations and MET:amplification and NOT EGFR:T790M	Non-small cell lung cancer	Gefitinib + Capmatinib	Phase Ib/II study. Capmatinib plus gefitinib showed clinical activity in patients with EGFR-mutated, MET-dysregulated NSCLC who progressed on EGFR-TKI, particularly in those with high MET-amplified tumors (ORR 47% with MET gene copy number ≥ 6), addressing a predominant EGFR-TKI resistance mechanism.	30156984
GIMR	2020-06-29	FL	4	EGFR+MET	EGFR:T790M and MET:amplification	Non-small cell lung cancer	Osimertinib + Crizotinib	Case report. MET amplification emerged as a resistance mechanism after T790M positivity in EGFR-mutant NSCLC, and was effectively targeted with a combination of crizotinib and osimertinib, showing tolerability and efficacy.	28274743
GIMR	2020-06-29	FL	4	EGFR+MET	EGFR:T790M and MET:amplification	Non-small cell lung cancer	Osimertinib + Crizotinib	Case report. EGFR-mutant NSCLC patient with emergent MET amplification after disease progression on erlotinib had a sustained partial response to combination osimertinib and crizotinib, with MET amplification persisting as a resistance mechanism at CNS progression.	30881166
GIMR	2020-06-28	FL	4	EGFR+MET	MET:Alteration and EGFR:Oncogenic mutations	Non-small cell lung cancer	Amivantamab		10.1200/JCO.2019.37.15_suppl.9009
GIMR	2024-06-02	FL	4	EGFR+MET	MET:overexpression AND NOT EGFR:oncogenic mutation	Non-small cell lung cancer	Telisotuzumab Vedotin	Phase 2. LUMINOSITY. NCT03539536.. N=161. Telisotuzumab vedotin showed ORR of 34.6% in c-Met high and 22.9% in EGFR wildtype, c-Met intermediate NSCLC patients, with a median DOR of 9.0 months and 7.2 months respectively. cMET status was determined by IHC intense staining with a cut-off at 50% (high) or 25% (intermediate) of cells.	10.1200/JCO.2024.42.16_suppl.103
GIMR	2023-04-05	FL	4	EGFR+RBM10	EGFR:Oncogenic mutations and RBM10:Loss-of-function mutations	Non-small cell lung cancer	Osimertinib + Navitoclax	Preclinical study. In RBM10-loss xenograft models, adding BH3-mimetic to Osimertinib leads to restored apoptosis in EGFR-mutant cells that have a RBM10-null condition.	35579943
GIMR	2022-09-07	FL	4	EGFR+RET	EGFR:Exon 19 deletion and EGFR:T790M and RET:ANK3-RET fusion	Non-small cell lung cancer	Osimertinib + Pralsetinib	Case report. Acquired resistance of ANK3-RET fusion following treatment to know EGFR mutations. Durable response of >12 months to Osimertinib and Pralsetinib combination.	35797511
GIMR	2020-10-05	FL	4	EGFR+RET	EGFR:Oncogenic mutations and RET:fusion	Non-small cell lung cancer	Osimertinib + Pralsetinib	Preclinical study and case reports. RET fusions, such as CCDC6-RET, were identified as a mechanism of acquired resistance to osimertinib in EGFR-mutant NSCLC, and combined EGFR and RET inhibition with osimertinib and BLU-667 showed effectiveness in treating patients with RET-mediated resistance.	30257958
GIMR	2020-10-05	FL	4	EGFR+ROS1	EGFR:Oncogenic mutations and ROS1:fusion	Non-small cell lung cancer	Osimertinib + Crizotinib	Preclinical study. GOPC-ROS1 rearrangement identified as an acquired resistance mechanism to osimertinib, with observed response to crizotinib combined treatments in lung adenocarcinoma.	29935846
GIMR	2021-06-23	JG	4	EIF1AX	A113_splice, N-terminal tail mutation, G6_splice, G8V, G9, K10N, R13, G15D	Thyroid cancer	AZD8055; AZD8055 + Trametinib; AZD8055 + JQ1; JQ1; Trametinib	Cell line model showing mutations in EIF1AX cooperate with RAS via ATF4/c-MYC and generates vulnerability to mTOR kinase inhibitors.	30305285
GIMR	2021-06-23	JG	4	EIF1AX+NRAS	EIF1AX:Oncogenic mutations and NRAS:Oncogenic mutations; EIF1AX:A113splice and NRAS:Oncogenic mutations	Thyroid cancer	AZD8055; AZD8055 + Trametinib; AZD8055 + JQ1; JQ1; Trametinib	Cell line model showing mutations in EIF1AX cooperate with RAS via ATF4/c-MYC and generates vulnerability to mTOR kinase inhibitors.	30305285
GIMR	2025-03-16	FL	4	EIF4EBP1	Protein expression	Breast cancer	Everolimus + Exemestane	Exploratory biomarker study. NCT02444390. SAFIRTOR. p4EBP1 staining was associated with treatment outcome in ER-positive endocrine-resistant metastatic breast cancer patients treated with everolimus and exemestane, with high-p4EBP1 associated with higher CBR (62% vs 40%) and longer PFS (9.2 vs 5.8 months). Positive staining was defined as p4EBP1 staining with Allred score >=6.	38182687
GIMR	2020-10-26	FL	4	EMSY	Amplification; Overexpression	Ovarian cancer	Cisplatin; Carboplatin; Platinum-based antineoplastic agent	Retrospective High grade ovarian cancer; Functional HR-deficient phenotype	31154673
GIMR	2021-12-02	FL	4	EPAS1	A530E (germline); Oncogenic mutations (germline)	Paraganglioma; Somatostatinoma; Polycythemia vera	Belzutifan	Case report of Pacak-Zhuang syndrome. Treatment with belzutifan led to a rapid and sustained tumour and biochemical response with resolution of polycythemia.	34818480
GIMR	2021-11-24	FL	4	EPHA7	Oncogenic mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody; Anti-CTLA-4 monoclonal antibody; Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody	Retrospective study showing EPHA7 mutant cancers have better clinical outcomes(higher ORR 53% vs 29% wild type, and duration of clinical benefit, 70 vs 43%) in cancer patients treated with immune checkpoint inhibitors	33526018
GIMR	2021-03-07	FL	4	ERBB2	A775_G776insYVMA (Y772_A775dup)	Non-small cell lung cancer	Afatinib	1 PR and 2SD in retrospective case series	23610105
GIMR	2020-04-16	FL	4	ERBB2	A775_G776insYVMA (Y772_A775dup), P780_Y781insGSP (G778_P780dup), G776	Non-small cell lung cancer	Afatinib	Case series.	22325357
GIMR	2025-06-09	FL	4	ERBB2	Amplification	Biliary tract cancer; Ovarian cancer	Trastuzumab deruxtecan	Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).	10.1200/JCO.2025.43.16_suppl.3020
GIMR	2022-09-07	FL	4	ERBB2	Amplification	Endometrioid endometrial cancer; Endometrial cancer	Afatinib	Case report. Partial response observed two months after afatinib.	31308701
GIMR	2026-03-04	FL	4	ERBB2	Amplification	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. Note 1 case of ERBB2 amplification had best response of PD.	40554742
GIMR	2022-11-01	FL	4	ERBB2	Amplification and D769Y	Breast cancer	Neratinib	Xenograft model. Neratinib was shown to reduce tumour volume in a breast cancer PDX model that harbour both ERBB2 amplification and HER2 D769Y mutation	30301790
GIMR	2022-11-01	FL	4	ERBB2	Amplification and L755S, Amplification and A775_G776insTVMA, Amplification and V777L, Amplification and L313I, Amplification and R456C, Amplification and D769Y	Breast cancer	Neratinib	In retrospective series, Neratinib was seen to confer clinical benefit in breast cancer that harbour both ERBB2 amplification and oncogenic mutations	30301790
GIMR	2022-05-11	FL	4	ERBB2	Amplification and S310F	Colorectal adenocarcinoma	Trastuzumab + Lapatinib	Case report.	34214965
GIMR	2025-02-05	FL	4	ERBB2	Amplification, Overexpression	Breast cancer	BBO-10203	Preclinical study. BBO-10203 demonstrates reduction of RAS-driven PI3Ka activity while maintaining normal glucose metabolism, exhibiting potent signaling pathway inhibition at low nanomolar concentrations and showing activity in PIK3CA-mutant and HER2-amplified human xenograft models.	10.1158/1538-7445.SABCS23-RF02-02
GIMR	2022-04-22	FL	4	ERBB2	Amplification, Overexpression	Breast cancer	Tucatinib + Trastuzumab	Phase 1. NCT01921335. Dose escalation trial. Combination of trastuzumab and tucatinib was shown to be safe and have preliminary intracranial activities at both BD and daily dosing regimens, including subjects with prior exposure to neratinib and/or lapatinib.	32461105
GIMR	2023-06-23	FL	4	ERBB2	Amplification, Overexpression	Ovarian mucinous carcinoma	Trastuzumab + Carboplatin	Case report. A significant response was observed in this case report of mucinous carcinoma with HER2 overexpression and amplification when treated with trastuzumab and carboplatin therapy.	20003286
GIMR	2022-04-22	FL	4	ERBB2	Amplification, Overexpression	Solid tumours	Tucatinib + Trastuzumab	Preclinical study showing activity of tucatinib as single-agent or in combination of trastuzumab across PDX models of several cancer types.	32241871
GIMR	2020-05-31	FL	4	ERBB2	Amplification; Alteration	Gastric cancer; Gastroesophageal junction adenocarcinoma; Colorectal adenocarcinoma	Trastuzumab deruxtecan	If amplified should check IHC	31825192
GIMR	2020-06-15	FL	4	ERBB2	D769H, D769Y, L755S, V777L, L755P, A775_G776insYVMA (Y772_A775dup), Exon 20 insertion, L786V, V842I, L869R	Solid tumours; Non-small cell lung cancer	Poziotinib	Cell-line evidence	31588020
GIMR	2020-06-15	FL	4	ERBB2	D769H, D769Y, L755S, V777L, L755P, L786V, V842I, L869R	Solid tumours; Non-small cell lung cancer	Afatinib; Dacomitinib; Neratinib		31588020
GIMR	2020-06-15	FL	4	ERBB2	D769H, D769Y, V777L	Solid tumours; Non-small cell lung cancer	Lapatinib		31588020
GIMR	2020-06-15	FL	4	ERBB2	D769H, D769Y, V777L, L786V, V842I, L869R 	Solid tumours; Non-small cell lung cancer	Pyrotinib		31588020
GIMR	2020-10-05	FL	4	ERBB2	D769H, I767N, R678Q, S310F, S310Y	Breast cancer	Trastuzumab		32256585
GIMR	2020-05-15	FL	4	ERBB2	D769Y, D742N	Non-small cell lung cancer	Pyrotinib	Case report. ERBB2 D769Y and D742N mutations are sensitive to pyrotinib, showing partial response to treatment with the combination of gefitinib and pyrotinib overcoming HER2-mediated resistance to gefitinib.	32327210
GIMR	2022-03-30	FL	4	ERBB2	D769Y, R896C 	Breast cancer	Lapatinib + Trastuzumab	Preclinical study. Activating HER2 mutations identified in 25 breast cancer patients lacking HER2 gene amplification were functionally characterized, showing sensitivity to neratinib, an irreversible HER2 inhibitor, but variable response to lapatinib.	23220880
GIMR	2021-03-17	FL	4	ERBB2	ERBB2:amplification and KRAS:G12D	Colorectal adenocarcinoma	Trastuzumab Emtansine	Single case report of durable response (15 months) with partial regression of metastases in trastuzumab-resistant disease.	32913966
GIMR	2021-03-11	FL	4	ERBB2	Exon 16 skipping mutation	Non-small cell lung cancer	Afatinib	Preclinical study. HER2 ex16 deletion, a novel HER2 splice variant, was identified as a potential osimertinib resistance mechanism in EGFR L858R/T790M-positive NSCLC, and its resistance was synergistically reversed by combining osimertinib with afatinib.	31557536
GIMR	2021-12-29	FL	4	ERBB2	Exon 20 insertion	Solid tumours	Tarloxotinib	Cell line and xenograft study. Tarloxotinib-E showed activities in the inhibition of two models harboring EGFR exon 20 insertion mutations.	33355298
GIMR	2025-06-04	FL	4	ERBB2	Exon 20 insertion mutation, A775_G776insYVMA (Y772_A775dup), G776delinsVC, S310F, S335C, L755S	Non-small cell lung cancer	Sevabertinib	Preclinical study. BAY 2927088 showed strong antiproliferative activity against various HER2 mutations, including exon 20 insertion mutations (A775insYVMA, G776delinsVC) and point mutations (S310F, S335C, L755S), in isogenic Ba/F3 cell lines and patient-derived xenograft models.	10.1158/1538-7445.AM2023-4035
GIMR	2021-12-29	FL	4	ERBB2	Exon 20 insertion, A775_G776insYVMA (Y772_A775dup)	Solid tumours	Tarloxotinib	Cell line and xenograft studies, and one case report. Tarloxotinib-E inhibits MDA-MB-175VIII cell line harboring HER2 exon 20 insertion or amplifications. Response in a clinical case report with ERBB2 A775_Y776insYVMA was seen.	33355298
GIMR	2023-11-22	FL	4	ERBB2	Exon 20 insertion, A775_G776insYVMA (Y772_A775dup), G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVCS310Y, R678Q, L755S, L755P, D769N, V773M, V777L, L869R, L869R and T798I, V842I	Solid tumour	ELVN-002	Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells.	10.1158/1538-7445.AM2023-4019
GIMR	2020-05-15	FL	4	ERBB2	Exon 21 mutation	Colorectal adenocarcinoma	ERBB2 inhibitor		31588020
GIMR	2026-03-03	FL	4	ERBB2	Extracellular domain mutation, S310Y, D277Y, S113F, Transmembrane domain mutations, G660D, Intracellular domain mutations, P1199S 	Non-small cell lung cancer	Zongertinib	Phase 1a-1b trial. NCT04886804. Zongertinib showed clinical benefit in patients with previously treated HER2-mutant NSCLC. ORR was 30% (Cohort 3) with variable responses seen in selected extracellular,  transmembrane, and intracellular domain mutations	40293180
GIMR	2025-05-24	FL	4	ERBB2	Extracellular domain mutation, Transmembrane domain, Intracellular domain, S310F, S310Y, D277Y, S113F, V659E, G660D, P1199S	Non-small cell lung cancer	Zongertinib	Phase 1a/b trial. NCT04886804. Zongertinib demonstrated clinical benefit in HER2-mutant NSCLC patients, with objective response rates of 71% (120mg dose), 48% (Cohort 5), and 30% (Cohort 3), and a median PFS of 12.4 months.	40293180
GIMR	2021-03-17	FL	4	ERBB2	Extracellular domain mutations; transmembrane domain mutations	Solid tumours	Lapatinib; Afatinib; Neratinib; Osimertinib	High throughput screening of VUS in ERBB2	29967253
GIMR	2022-03-30	FL	4	ERBB2	G309A, V777L, D769H, V842I, L755S, L755_759del	Breast cancer	Neratinib	Preclinical study. HER2 somatic mutations identified in 25 breast cancer patients without HER2 gene amplification, with 7 activating mutations sensitive to neratinib, suggesting potential benefit of HER2-targeted therapy.	23220880
GIMR	2020-12-09	FL	4	ERBB2	G660D and S310F, G660D, V659E, V659D	Solid tumours	Afatinib	Transmembrane mutation. ERBB2 TKIs, such as lapatinib, neratinib, pyrotinib, and poziotinib hypothesised to have antitumour activity.	29146616
GIMR	2022-02-08	FL	4	ERBB2	G776V	Breast cancer	Pertuzumab + Trastuzumab	Case report. Concomitant PIK3CA (H1047R) and two MAP3K1 frameshift mutations. Duration of treatment on Nab-paclitaxel + Pertuzumab + Trastuzumab was 11 months.	10.1200/PO.16.00037
GIMR	2020-05-15	FL	4	ERBB2	Kinase domain mutation, S310, exon 20 insertion	Solid tumours	Neratinib	Phase 1/2 SUMMIT trial. NCT01953926. Neratinib showed activity in Her2 S310, Kinase domain hotspot, and some exon 20 insertion  hotspot mutations	29420467
GIMR	2021-06-16	FL	4	ERBB2	L755S	Breast cancer	Trastuzumab Emtansine; Poziotinib	HER2+ BT474 cell model study	10.1158/1538-7445.SABCS20-PD3-09
GIMR	2020-10-05	FL	4	ERBB2	L755S, V777L, D769H, I767M, R678Q, S310F, S310Y	Breast cancer	Neratinib; Afatinib		32256585
GIMR	2022-04-22	FL	4	ERBB2	L755S, V777L, S310Y, G776delinsVC, G776delinsVG	Solid tumours	Tucatinib	Tucatinib demonstrated activites in PDX models harbouring activating HER2 mutations.	10.1158/1538-7445.AM2020-4222
GIMR	2023-04-12	FL	4	ERBB2	L869R	Breast cancer	Neratinib	Case report of a lobular breast carcinoma harboring ERBB2 L869R is sensitive to Neratinib with clinical response.	28274957
GIMR	2021-05-20	FL	4	ERBB2	MDK-ERBB2 fusion, Fusions	Gastric cancer	Trastuzumab; Trastuzumab Emtansine	Biomarker analysis. Whole-transcriptome sequencing identified 3 novel HER2 fusions (ZNF207-HER2, MDK-HER2, and NOS2-HER2) in 14% of 21 HER2-amplified gastric cancer samples. Trastuzumab showed activity in MDK-HER2 but not ZNF207-HER2 expressing xenografts due to differential binding.	25889497
GIMR	2020-04-16	FL	4	ERBB2	Oncogenic mutations	Lung adenocarcinoma	Afatinib	Phase 2 study. In Cohort 3, one unconfirmed response from seven patients (5 SD). Note individual and concomitant mutations not reported.	25682316
POTTR	2020-04-16	FL	4	ERBB2	Oncogenic mutations	Solid tumours	anti-ERBB2 monoclonal antibody	Check Tier	29320312, NCT02091141
GIMR	2023-07-18	FL	4	ERBB2	Oncogenic mutations, Amplification	Solid tumours	BI-1810631	Beamion Lung 1 . NCT04886804. Preliminary data showed responses seen in oesophageal carcinoma and cholangiocarcinoma.	36528522; JCO.2023.41.16_suppl.8545
GIMR	2023-12-26	FL	4	ERBB2	Overexpression	Extramammary Paget’s disease	Trastuzumab + Pertuzumab + Paclitaxel	Case report. Single complete responder to pertuzumab, trastuzumab, and weekly paclitaxel.	37595182
GIMR	2020-12-18	FL	4	ERBB2	Overexpression	Solid tumours	Margetuximab	Phase 1 study. NCT01148849. N=66. Margetuximab showed single-agent activity in patients with HER2-positive advanced solid tumors, with 12% (7/60) confirmed partial responses and 50% (30/60) stable disease, including durable responses in breast cancer patients.	28119295
GIMR	2025-06-12	FL	4	ERBB2	Overexpression	Solid tumours	VVD-442	Preclinical study. Covalent binding to C242 in the PI3K p110 alpha RBD inhibits RAS-PI3K interaction, suppressing growth of RAS mutant and HER2 over-expressing tumors without inducing hyperglycemia.	10.1101/2024.12.17.629001
GIMR	2025-02-09	FL	4	ERBB2	Overexpression, Amplification	Breast cancer	VRN101099	Preclinical study. VRN101099, a brain-permeable HER2 kinase inhibitor, showed anti-tumor activity in HER2-positive cancer models with nanomolar potency.	10.1158/1538-7445.SABCS22-P1-11-03
GIMR	2024-10-04	FL	4	ERBB2	Overexpression, Amplification	Breast cancer	ZN-1041	Phase 1, ZN-A-1041-101-US (NCT05593094). N=10. 1 pt achieved confirmed PR at 400 mg BID dose for >15 months	10.1200/JCO.2023.41.16_suppl.1041
GIMR	2020-05-31	FL	4	ERBB2	Overexpression, Amplification	Non-small cell lung cancer	Trastuzumab deruxtecan	DESTINY-Lung01, no data available yet. Hypothesis generating	10.1200/JCO.2020.38.15_suppl.9504
GIMR	2023-12-06	FL	4	ERBB2	Overexpression, Amplification	Solid tumour	GQ1001	Preclinical study. GQ1001, a next-generation HER2-targeting ADC, demonstrated robust anti-tumor activity in HER2-positive models, including those resistant to anti-HER2 TKIs and/or mAbs, with enhanced linker stability and reduced off-target toxicity.	10.1158/1538-7445.AM2023-2702
GIMR	2025-05-28	FL	4	ERBB2	Overexpression, Amplification	Solid tumour	GQ1001	Phase Ia study. NCT04450732. GQ1001, a HER2-targeting ADC, showed  antitumor activity in HER2-positive advanced solid tumors, with 6 out of 15 evaluable subjects achieving confirmed partial response at doses ≥ 7.2 mg/kg, and a median progression-free survival of 4.8 months.	10.1158/1538-7445.AM2023-CT178
GIMR	2025-07-17	FL	4	ERBB2	Overexpression, Amplification	Solid tumours	Cinrebafusp alfa	Phase 1. NCT03330561. First-in-human study. Cinrebafusp alfa, a HER2/4-1BB bispecific molecule, was evaluated in N=40 patients with previously treated HER2-positive malignancies. The objective response rate was 12.5%, with confirmed responses of 28.6% at 8 mg/kg and 25.0% at 18 mg/kg. Disease control rate was 52.5%, and maximum tolerated dose was not reached.	39235868
GIMR	2022-07-18	FL	4	ERBB2	Overexpression, Protein expression, Amplification	Solid tumours	DB-1303, ARX788	Phase 1 trial eligibility 	NCT05150691, NCT03255070
GIMR	2022-08-10	FL	4	ERBB2	Overexpression, Protein expression, Low protein expression	Solid tumours	AMX-818		10.1158/1535-7163.TARG-21-P193
GIMR	2024-12-02	FL	4	ERBB2	p95 expression	Breast cancer	Lapatinib	Preclinical study. HER2-overexpressing breast cancer cells expressing p95HER2 were resistant to trastuzumab, but sensitive to lapatinib, with significant growth inhibition and tumor regression in xenograft models	17440164
GIMR	2021-06-06	FL	4	ERBB2	Protein expression and NOT Amplification, Low protein expression and NOT Amplification	Biliary tract cancer	Trastuzumab deruxtecan	JMA-IIA00423. ORR of 12.5% (1 of 8) median of PFS 4.2 months, and ,edoam OS of 8.9 months.	10.1200/JCO.2022.40.16_suppl.4006
GIMR	2021-06-07	FL	4	ERBB2	Protein expression, Low protein expression	Triple-negative breast cancer	Durvalumab + Paclitaxel + Trastuzumab deruxtecan	BEGONIA Arm 6: Confirmed ORR 4/4. Ongoing enrollment. NCT03742102.	10.1200/JCO.2021.39.15_suppl.1023
GIMR	2022-03-30	FL	4	ERBB2	Protein expression, Overexpression	Breast cancer; Gastric cancer; Gastroesophageal junction adenocarcinoma	MT-5111		10.1200/JCO.2020.38.4_suppl.433, 10.1158/1538-7445.SABCS19-P1-18-35
GIMR	2023-03-30	FL	4	ERBB2	Protein expression, Overexpression, Amplification	Solid tumours	YH32367		10.1016/j.annonc.2021.08.1066
GIMR	2020-04-16	FL	4	ERBB2	Q57R, S250C, E265K, E395K, G815R	Lung squamous cell carcinoma	Afatinib	Retrospective analysis from LUX-8. However, unable to distinguish response to treatment with afatinib or tumour biology of disease.	29902295
GIMR	2023-01-11	FL	4	ERBB2	R188C	Acute lymphoblastic leukaemia	Afatinib; Neratinib; Poziotinib		32366937
GIMR	2023-01-11	FL	4	ERBB2	R188C, P489L, L1157R	Acute myeloid leukaemia	Afatinib; Neratinib; Poziotinib	Preclinical study. ERBB2 mutations (R188C, P489L, and L1157R) identified in leukaemia patients are oncogenic and sensitive to irreversible pan-HER inhibitors, such as afatinib, neratinib, and poziotinib, with nanomolar IC50 values, and to trastuzumab, particularly for extracellular domain mutants. Updated: 2025-05-28	32366937
GIMR	2023-09-05	FL	4	ERBB2	R188C, P489L, L1157R	Acute myeloid leukaemia; Acute lymphoblastic leukaemia	Afatinib; Poziotinib; Poziotinib		32366937
GIMR	2023-09-05	FL	4	ERBB2	R188C, P489L, L1157R	Acute myeloid leukaemia; Acute lymphoblastic leukaemia	Gefitinib; Erloginib; Lapatinib; Canertinib; Pelitinib		32366937
GIMR	2020-06-09	FL	4	ERBB2	S310F	Extramammary Paget’s disease	Lapatinib + Capecitabine	Case report. A patient with metastatic extramammary Paget's disease associated with adnexal adenocarcinoma harbouring ERBB2 S310F mutation responded to anti-HER2 drugs.	25085898
GIMR	2020-06-09	FL	4	ERBB2	S310F	Extramammary Paget’s disease	Trastuzumab + Carboplatin	Case report. A patient with ERBB2(S310F) mutated metastatic extramammary Paget's disease initially responded to trastuzumab and carboplatin, but developed resistance with additional genomic alterations including ERBB3(A232V) and PIK3CA(G106V) mutations and MET and CDK6 amplification.	31803359
GIMR	2021-07-06	FL	4	ERBB2	S310F, S310Y, L403V, L755S, D769Y, A775_Y776insYVMA (Y772_A775dup), V777L, T862A	Breast cancer	Pyrotinib	Phase 2 trial. NCT03412383. Pyrotinib monotherapy achieved an ORR of 40% and CBR of 60% in HER2 amplification-negative, mutation-positive metastatic breast cancer patients, with a median PFS of 4.9 months. Responses or prolonged SD were seen in S310F, L755S, D769Y, V777L, T862A, and A775_Y776insYVMA (Y772_A775dup).	33145402
GIMR	2023-11-22	FL	4	ERBB2	S310F, S310Y, R678Q, D769N, V773M, V777L, V842I, P780_Y781insGSP (G778_P780dup), V777_G778insGC	Solid tumour	Tucatinib	Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells.	10.1158/1538-7445.AM2023-4019
GIMR	2020-09-15	FL	4	ERBB2	S310F, S653C, D277H and S310F	Urothelial carcinoma	Lapatinib; Afatinib	Preclinical study. ERBB2 mutations were found in 15% of urothelial bladder cancer cell lines, and these mutations enhanced ErbB2 activation and predicted a response to lapatinib, with 93% reversal of mutant-induced growth patterns.	24971884
GIMR	2022-01-05	FL	4	ERBB2	S335C	Non-small cell lung cancer	Pyrotinib	Case report. Partial response to pyrotinib in the non-tyrosine kinase domain mutation S335C.	33655632
GIMR	2021-03-17	FL	4	ERBB2	Transmembrane domain mutations	Solid tumours	Trastuzumab	High throughput screening of VUS in ERBB2	29967253
GIMR	2022-04-13	FL	4	ERBB2	V659E	Non-small cell lung cancer	Lapatinib; Afatinib; Trastuzumab Emtansine	Retrospective case series. Response with prolonged PFS in one case harbouring V659E with both small molecule TKI and antibody drug conjugate.	10.1200/JCO.2020.38.15_suppl.e21521
GIMR	2021-06-23	FL	4	ERBB2	V659E, G660D, G660R, R678Q, V697L, Q709, Transmembrane domain mutation, Juxtamembrane domain mutation	Solid tumours	Trastuzumab; Pertuzumab; Afatinib; Neratinib; Lapatinib	Preclinical study. Activating HER2 transmembrane and juxtamembrane domain mutations (G660D, R678Q, E693K, Q709L) identified in patient tumors were found to be sensitive to anti-HER2 antibodies and small-molecule kinase inhibitors, with a germline G660D mutant lung cancer patient showing clinical response to HER2 blockade.	30449325
GIMR	2025-04-30	FL	4	ERBB2	V777L, Amplification, D769H, A775_Y776insYVMA, G776delinsVC, Exon 20 insertion, L755A, L755M, L755P, L755S, S310A, S310F, S310Y, V777L, V777M, V842I	Breast cancer	Zongertinib	Preclinical study & Case series. Zongertinib, a covalent HER2 TKI, exhibits antitumor activity in HER2-dependent NSCLC xenografts and induces objective responses in HER2-driven cancers, including SDC4-NRG1 fusion-positive cholangiocarcinoma and HER2 V777L-mutant breast cancer. 	39248702
GIMR	2020-10-05	FL	4	ERBB2	V777L, D769H, I767N, Q678Q, S310F, S310Y	Breast cancer	Lapatinib		32256585
GIMR	2021-11-30	FL	4	ERBB2	V777L, D769H, V842I, L755S, R678Q, G309A	Breast cancer	Neratinib	Cell line and xenograft studies showing sensitivity to neratinib in selected ERBB2 kinase domain, juxtamembrane, and extracellular domain mutations.	23220880
GIMR	2022-08-30	FL	4	ERBB2+ERBB3	ERBB2:Oncogenic mutation and ERBB3:E928G, ERBB2:S310F and ERBB3:E928G, ERBB2:L755S and ERBB3:E928G, ERBB2:V777L and ERBB3:E928G, ERBB2:L869R and ERBB3:E928G	Breast cancer	Neratinib + Alpelisib	Cell-line study. HER2/HER3 co-mutations activate PI3K signaling pathways in tumour cells, resulting in resistance to HER2 inhibitors. The co-operative activation of HER2/HER2 is sensitive to combined inhibition with Both HER2 and PI3K inhibitors.	34171264
GIMR	2024-06-09	FL	4	ERBB2+ESR1	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Breast cancer	PF-07248144	Phase 1. NCT04606446. N=78. Durable response of PF-07248144 was seen in heavily pretreated ER+ HER2- metastatic breast cancer. ORR was 11% as monotherapy and 30% in combination with fulvestrant. Median PFS was 10.7 months.	38822758, 10.1200/JCO.2024.42.16_suppl.3006
GIMR	2021-03-17	FL	4	ERBB2+KRAS	ERBB2:amplification and KRAS:G12D	Colorectal adenocarcinoma	Trastuzumab Emtansine	Single case report of clinical response with partial regression of lung metastases (overall stable disease). Post-exposure to trastuzumab and pertuzumab.	32023524
GIMR	2022-08-30	FL	4	ERBB3	E928G, Q865H, S864I	Solid tumours	Afatinib; Trastuzumab + Lapatinib	Case series. Treatment with lapatinib and afatinib resulted in prolonged PFS ratio in one case each of breast cancer, cholangiocarcinoma, and lung squamous cell carcinoma. The benefits seen were in cases where simple mutations occur at the ERBB3 kinase domain.	29413684
SuboKB	2020-04-16	ST	4	ERBB3	G284R	Breast cancer	Lapatinib + Trastuzumab	Case report. Third-line therapy in HER2-negative breast cancer led to complete metabolic response and radiological partial response.	25953157
SuboKB	2020-04-16	ST	4	ERBB3	G284R, V104M, R103G	Urothelial carcinoma	Afatinib	Phase 2. Platinum-Refractory metastatic urothelial carcinoma. Pre-defined patient selection based on ERBB aberrations. While overall the trial did not meet the primary point of PFS3, three patients with ERBB3 mutations achieved PFS at 3 months. 	27044931
GIMR	2021-07-28	FL	4	ERBB3	Overexpression	Colorectal adenocarcinoma	H3Mab-17	Preclinical study. Anti-HER3 monoclonal antibody H(3)Mab-17 showed antitumor activity, inducing ADCC and CDC against Caco-2 cells and significantly reducing tumor growth in a Caco-2 xenograft model.	34184091
GIMR	2021-05-17	FL	4	ERBB3	Overexpression	Prostate cancer	Patritumab deruxtecan	Cell line and DX model studies. Antitumor activity was demonstrated in the in vitro HER3-positive prostate cancer cell lines, as well as activity against the HER3 high PDX model. 	34753775
GIMR	2025-05-20	FL	4	ERBB3	Overexpression, Protein expression, Low protein expression	Solid tumours	AMT-562	Preclinical study. AMT-562, a novel HER3-targeting antibody-drug conjugate, demonstrated potent and durable antitumor responses in low HER3 expression xenograft models, including digestive system and lung tumors, and showed a favorable pharmacokinetic and safety profile.	37302522
GIMR	2022-05-18	FL	4	ERBB3	P262H, G248R, Q809R	Solid tumours	Lapatinib		23680147
SuboKB	2020-04-23	ST	4	ERBB3	Protein expression	Solid tumours	Anti-ERBB3 monoclonal antibody	ph I studies	29420467
GIMR	2021-12-17	FL	4	ERBB3	Protein expression	Solid tumours	GSK2849330	Phase 1. NCT01966445. Escalation and expansion cohort. HER3 positivity is defined by IHC. N=29. No responders apart from 1 PR which harbours NRG1 fusion, 7 SD, 16 PD.	34132450
GIMR	2021-02-12	FL	4	ERBB3	Protein expression, Overexpression	Solid tumours	Patritumab deruxtecan	Preclinical drug development study. U3-1402 demonstrated dose-dependent and HER3-dependent antitumor activity in PDX tumors with HER3 expression	31471314
GIMR	2021-11-10	FL	4	ERBB3	V104L	Gastric cancer	Pyrotinib + Irinotecan		33500629
GIMR	2023-08-31	FL	4	ERBB3	V104M, A232V, P262H, G284R, Q809R, S846I, E928G	Breast cancer	Patritumab deruxtecan	Cell line study. Patritumab deruxtecan demonstrated in vitro activity against breast cancer cell line transduced to expressmutated HER3.	35503762
GIMR	2025-07-17	FL	4	ERBB4	E715K, R687K	Solid tumours	Afatinib; Neratinib; Dacomitinib	Preclinical study. Unbiased functional genetics screen identifies rare activating ERBB4 mutations (E715K, R687K) promoting hyperactivity in cell models, growth in 2D/3D cultures, and in vivo tumor growth; all mutants sensitive to pan-ERBB inhibitors afatinib, neratinib, dacomitinib.	36860695
SuboKB	2020-04-16	ST	4	ERBB4	Oncogenic mutations	Non-small cell lung cancer; Melanoma	Lapatinib + Afatinib		29902295
GIMR	2020-10-05	FL	4	ERCC1	Loss of protein expression; Oncogenic mutations	Mesothelioma; Ovarian cancer; Cervical cancer	Cisplatin; Platinum-based antineoplastic agent		22031231, 19574766, 16144907, 32564128, 28659181
GIMR	2020-05-27	FL	4	ERCC2	Oncogenic mutations	Urothelial carcinoma	Cisplatin; Platinum-based antineoplastic agent	Downgraded; Preclinical data only; pending prospective trial	29980530, 25096233, 30290956, 28027876, 27449101
GIMR	2020-11-17	FL	4	ERRFI1	E384X, Loss-of-function mutations, deletion	Cholangiocarcinoma	Erlotinib	Case report	24550739
GIMR	2024-09-02	FL	4	ESR1	D538G, Y537S, D538G, Y537S	Breast cancer	ERX-315	Preclinical study. ERX-315 induced endoplasmic reticulum stress leading to cancer cell death in mutant estrogen receptor alpha -driven breast cancer cell lines.	10.1158/1538-7445.SABCS23-PO3-26-11
GIMR	2022-06-17	FL	4	ESR1	F404L, D538G and F404L, E380Q and F404L	Breast cancer	AZD9833; Elacestrant; Tamoxifen	Novel ESR1 F404 mutations (F404L, F404I, and F404V) were acquired in 4% of patients in the plasmaMATCH Cohort A trial (NCT03182634, N=69). These mutations confer resistance to fulvestrant when combined with preexisting activating ESR1 mutations. In cell line models, F404L demonstrates sensitivity to tamoxifen and select SERDs. These mutations may be potentially targetable by oral ERalpha degraders in clinical development.	10.1200/JCO.2022.40.16_suppl.1009
GIMR	2022-12-07	FL	4	ESR1	Fusion, ESR1-YAP1 fusion, ESR1-PCDH11X fusion	Breast cancer	Palbociclib	Preclinical study. ESR1 gene fusions in ER-positive breast cancer confer estrogen-independent growth, anti-estrogen resistance, and metastatic progression, but remain sensitive to CDK4/6 inhibitors.	30089255
GIMR	2020-04-16	FL	4	ESR1	Protein expression	Breast cancer	AZD9496	Phase 1 trial. AZD9496, an oral selective estrogen receptor degrader, showed evidence of prolonged disease stabilization in heavily pretreated ER(+)/HER2(-) advanced breast cancer patients, with a partial response in one patient and stable disease at 12 months in four patients.	29440181
GIMR	2021-06-07	FL	4	ESR1	Protein expression	Breast cancer	Giredestrant	NCT03332797	10.1200/JCO.2021.39.15_suppl.1017
GIMR	2023-12-06	FL	4	ESR1	Protein expression	Breast cancer	INX-315	Preclinical study. INX-315 induces senescence in CCNE1-amplified luminal breast cancer cell lines, leading to growth control and overcoming and delaying breast cancer resistance to CDK4/6i.	38047585
POTTR	2020-04-26	FL	4	ESR1	Protein expression	Endometrial cancer	Letrozole; Anastrozole	Systematic review	31134155
GIMR	2022-06-19	FL	4	ESR1	Protein expression, D538G, Y537S	Breast cancer	Lasofoxifene + Abemaciclib		10.1200/JCO.2022.40.16_suppl.1022
GIMR	2022-05-25	FL	4	ESR1	Protein expression, Oncogenic mutations	Breast cancer	Palazestrant	Phase 1b/2 study. NCT0526610. N=33. Palazestrant + Palbociclib were well tolerated with 55% grade 3 and 9% grade 4 neutropenia. 4 partial responses (2 confirmed) out of 19 response-evaluable patients with a CBR of 42% across all patients and 67% in patients with ESR1 mutations.	10.1158/1538-7445.SABCS23-PS15-04
GIMR	2022-05-25	FL	4	ESR1	Protein expression, Oncogenic mutations, Y537S, D538G	Breast cancer	Palazestrant	Preclinical study. Palazestrant (OP-1250), a novel oral complete estrogen receptor antagonist, demonstrated superior efficacy and pharmacokinetic properties compared to fulvestrant, elacestrant, and tamoxifen in ER-positive breast cancer models, including wild-type and ESR1-mutant xenografts and intracranial implants. Updated: 2025-05-28	38102750
GIMR	2022-06-19	FL	4	ESR1	Protein expression, Y537, D538, E380, L536	Breast cancer	Imlunestrant	Phase 1. EMBER. In advanced breast cancerpatients, ORR was 8% (6/75). CBR was 40.4% (42/104). In endometriod cancer patients, ORR was 5% (1/20). CBR was 47%. CBR seen regardless of ESR1 mutation.	10.1200/JCO.2022.40.16_suppl.1021
GIMR	2021-06-07	FL	4	ESR1	Protein expression, Y537S	Breast cancer	H3B-6545	Phase 1/2: ORR 17% (12/72) at RP2D in heavily pretreated patients and visceral metastases. 7/10 PR and SD seen in clonal Y537S mutation.	10.1200/JCO.2021.39.15_suppl.1018
GIMR	2021-02-02	FL	4	ESR1	Y537S, D538G, Y537N, E380Q, L536H, L536P	Breast cancer	Elacestrant	Objective responses seen in 5 of 15 (33%) patients. 	33513026
GIMR	2023-12-06	FL	4	ESR1+CCNE1	ESR1:Protein expression and CCNE1:Amplification	Breast cancer	INX-315	Preclinical study. INX-315 induces senescence in CCNE1-amplified luminal breast cancer cell lines, leading to growth control and overcoming and delaying breast cancer resistance to CDK4/6i.	38047585
GIMR	2025-03-15	FL	4	ESR1+ERBB2	ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression, ESR1:D538, ESR1:Y537	Breast cancer	PF-9363	Preclinical study. The selective KAT6A/KAT6B inhibitor demonstrated anti-tumor activity and growth suppression in KAT6-high ER+/luminal breast cancer models with or without ESR1 mutations associated with endocrine resistance.	37557181
GIMR	2024-06-02	FL	4	ESR1+ERBB2	NOT ESR1:protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression	Triple-negative breast cancer	Sacituzumab tirumotecan	Phase 3. OptiTROP-Breast01. NCT05347134. N=263. Sacituzumab tirumotecan significantly improved PFS over chemotherapy (5.7 vs 2.3 months) and OS (HR 0.53, median OS not reached vs 9.4 months). ORR 43.8% in advanced TNBC.	10.1200/JCO.2024.42.16_suppl.104
GIMR	2025-04-23	FL	4	ESR1+TP53	ESR1:Protein expression AND TP53:Oncogenic mutations	Breast cancer	Abemaciclib + AZD8421	Preclinical study. In metastatic hormone receptor-positive breast cancer, TP53 loss and MDM2 amplification were associated with lack of long-term disease control . CDK2 inhibition overcomes p53 loss, leading to geroconversion and senescence.	39532066
GIMR	2020-04-16	FL	4	EZH2	Oncogenic mutations, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V	Diffuse large B-cell lymphoma	GSK126	Preclinical study. EZH2 inhibition by GSK126 decreases global H3K27me3 levels, reactivates silenced PRC2 target genes, and inhibits proliferation of EZH2 mutant DLBCL cell lines and xenografts.	23051747
GIMR	2020-06-15	FL	4	EZH2	Oncogenic mutations, A677G, Y641N, Y641C, Y641H, Y641S, Y641F, Y646, A687V	Non-Hodgkin’s lymphoma	Tazemetostat	Preclinical study. EPZ-6438, a potent EZH2 inhibitor, showed antitumor activity in EZH2-mutant non-Hodgkin lymphoma models, with dose-dependent tumor growth inhibition and sustained tumor regressions, confirming EZH2 dependency in these cancers.	24563539
GIMR	2024-06-02	FL	4	F3	Protein expression	Solid tumours	MRG004A	Phase 1/2 study. N=63. MRG004A showed antitumor activity in heavily pretreated patients with solid tumors, including pancreatic cancer (ORR 33%, DCR 83%) at 2mg/kg.	10.1200/JCO.2024.42.16_suppl.3002
GIMR	2021-06-09	FL	4	FAM175A	Loss-of-function mutations	Breast cancer	Olaparib; PDD00017273	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
SuboKB	2020-04-16	FL	4	FANCA	Loss-of-function mutations	Prostate cancer	Rucaparib	Phase 2 TITRON2	32086346
SuboKB	2020-04-16	FL	4	FANCA	S1088F 	Solid tumours	Cisplatin	Preclinical study. Germline FANCA S1088F mutation disrupts FANC protein complex, resulting in increased sensitivity to DNA damaging agents, suggesting potential predictive biomarker for prostate cancer treatment response.	28864460
SuboKB	2020-04-16	FL	4	FANCC	Loss of protein expression	Head and neck squamous cell carcinoma 	Olaparib	Preclinical study. Fanconi anemia head and neck cancers acquired relative interstrand crosslinker resistance and PARP inhibitor sensitivity, with increased PARP-mediated DNA damage sensing and repair in Fanconi anemia-deficient cells.	25609062
GIMR	2021-03-16	FL	4	FANCC	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. Responder in Full eligible population	33583720
GIMR	2020-10-22	FL	4	FANCD2	Loss-of-function mutations, Oncogenic mutations	Non-small cell lung cancer	Veliparib	Cell line study only using FANCD2 knockout	25566506
SuboKB	2020-04-16	FL	4	FANCG	Oncogenic mutations	Pancreatic adenocarcinoma	KU-55933	Preclinical study. FA pathway-deficient tumor cells are sensitive to ATM inhibition, suggesting a potential therapeutic strategy for tumors with FA pathway dysfunction, particularly in cancers with FA pathway deficiency such as certain breast, ovarian, pancreatic, and hematological tumors.	17431503
GIMR	2020-04-25	FL	4	FANCG	Oncogenic mutations	Prostate cancer	Olaparib	FANCG mutation listed in TOPARP-B inclusion criteria. 1 case recruited only (castrate sensitive disease).	31806540
GIMR	2020-04-25	FL	4	FANCI	Oncogenic mutations	Prostate cancer	Olaparib	TOPARP-B. 1 Case	31806540
GIMR	2020-11-26	FL	4	FANCL	Oncogenic mutations	Prostate cancer	Olaparib	PROFound trial inclusion criteria but no recruitment. 	32343890, 32955174
GIMR	2021-03-16	FL	4	FANCM	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. 3 responders in Full eligible population	33583720
GIMR	2022-02-21	FL	4	FBXW7	Oncogenic mutations	Colorectal adenocarcinoma	Regorafenib + ABT-737	Cell line study. Selective Mcl-1 inhibitors restore regorafenib sensitivty in CRC cell lines due to FBXW7-associated intrinsic or acquired resistance.	27399335
GIMR	2025-06-13	FL	4	FBXW7	Oncogenic mutations	Solid tumours	Azenosertib	Preclinical study. Azenosertib demonstrated broad antitumor activity across solid tumors in Phase I monotherapy studies. Preclinical data revealed tumor growth inhibition >60% in CCNE1-amplified models (2/2) and FBXW7-mutated models (3/5).	34423975
SuboKB	2020-04-16	FL	4	FGF19	Amplification	Hepatocellular carcinoma	PRN1371	FGF19-FGFR4 signaling pathway is a potential target for HCC treatment, with various FGFR4/pan-FGFR inhibitors in different clinical trial phases, offering future perspectives for improving efficacy in relation to aberrant FGF19-FGFR4 expression.	31167419
SuboKB	2020-06-10	ST/FL	4	FGF19	Overexpression	Hepatocellular carcinoma	Fisogatinib	Preclinical and clinical study. Fisogatinib, a potent FGFR4 inhibitor, showed clinical activity in HCC patients with aberrant FGF19 expression, but resistance emerged with gatekeeper and hinge-1 mutations in FGFR4 kinase domain.	31575540
GIMR	2020-04-15	FL	4	FGFR1	Amplification	Breast cancer	Everolimus	Preclinical and clinical study. FGFR1 amplification is associated with endocrine resistance but retained sensitivity to mTOR inhibitor everolimus in hormone receptor-positive metastatic breast cancer, suggesting a potential therapeutic role for mTOR inhibitors in ER+, FGFR1+ metastatic breast cancer.	31371343
GIMR	2020-04-15	FL	4	FGFR1	Amplification	Breast cancer	Fulvestrant + Palbociclib + Erdafitinib	PDX study. Adding erdafitinib to palbociclib and fulvestrant induced complete responses FGFR1-amplified/ER+	30914635
GIMR	2020-06-11	FL	4	FGFR1	Amplification	Lung squamous cell carcinoma	Infigratinib	Responses in Phase 1 dose expansion	27870574, 10.1093/annonc/mdy424.030
GIMR	2022-02-21	FL	4	FGFR1	Amplification	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In the FGFR amplification group (N=26), a single responder was seen in FGFR1 amplification (ORR 3.8%)	35176457
GIMR	2020-06-11	FL	4	FGFR1	Amplification, Fusion, Oncogenic mutations and NOT V561	Solid tumours	Erdafitinib	Phase 1 study. NCT01703481. Erdafitinib showed clinical activity in advanced solid tumors with FGFR mutations or fusions, particularly in urothelial carcinoma (ORR 46.2%) and cholangiocarcinoma (ORR 27.3%), with median response durations of 5.6 and 11.4 months, respectively.	31088831
GIMR	2020-06-11	FL	4	FGFR1	Amplification, Oncogenic mutations	Lung squamous cell carcinoma	Erdafitinib	Phase 2 trial (FIND)	10.1016/j.jtho.2018.08.628
GIMR	2022-07-26	FL	4	FGFR1	FGFR1-PLAG1 fusion,  FGFR1-TACC1 fusion, M563T	Solid tumours	Futibatinib	NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14%. Responses were seen in two FGFR1 fusions and one urothelial carcinoma harbouring M563T and FGF3/FGF19 amplification.	34551969
GIMR	2020-06-11	FL	4	FGFR1	Fusion	Solid tumours	Zoligratinib	Cholangiocarcinoma: 2 PR. CRC: 1PR	10.1200/JCO.2020.38.15_suppl.3603
GIMR	2020-06-11	FL	4	FGFR1	Fusions	Solid tumours	AZD4547	Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.	32463741, 10.1200/JCO.2018.36.15_suppl.2503, 10.1200/jco.2014.32.15_suppl.8035
GIMR	2020-09-25	FL	4	FGFR1	N546D	Solid tumours	Futibatinib	Phase 1 trial. NCT02052778. FOENIX-101. N = 86. Futibatinib, a selective FGFR1-4 inhibitor, was evaluated in patients with refractory solid tumors with partial responses observed in FGFR2 fusion-positive intrahepatic cholangiocarcinoma (n = 3) and FGFR1-mutant primary brain tumor (n = 2).	32622884
GIMR	2022-02-21	FL	4	FGFR1	N546K	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In the FGFR mutation subgroup, ORR was 23% (3/13)	35176457
GIMR	2023-02-05	FL	4	FGFR1	Overexpression	Colorectal cancer	PD173074	Cell line study	31096734
GIMR	2021-02-02	FL	4	FGFR1	Overexpression	Urothelial carcinoma	Rogaratinib	Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation)	31405822
GIMR	2020-06-11	FL	4	FGFR2	Amplification	Gastroesophageal junction adenocarcinoma; Gastric Cancer	AZD4547	Conflicting data. 3/9 response in NCT01795768, 0% ORR in SHINE	10.1200/JCO.2015.33.15_suppl.2508, 29177434
GIMR	2022-02-21	FL	4	FGFR2	Amplification	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In the FGFR amplification group (N=26), a single responder was seen in FGFR1 amplification (ORR 3.8%)	35176457
GIMR	2022-07-26	FL	4	FGFR2	Amplification	Solid tumours; Gastric cancer	Futibatinib	NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14%. Responses was seen single case of gastric cancer harbouring FGFR2 amplification.	34551969
GIMR	2020-06-11	FL	4	FGFR2	Amplification, Fusion, Oncogenic mutations and NOT V564	Solid tumours	Erdafitinib	NCT01703481, ORR 46.2%	31088831
GIMR	2025-01-09	FL	4	FGFR2	BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N549K (N550K)	Cholangiocarcinoma	Futibatinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-02-21	FL	4	FGFR2	C382R	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In the FGFR mutation subgroup, ORR was 23% (3/13)	35176457
GIMR	2022-09-28	FL	4	FGFR2	Extracellular domain deletion, H167_N173del, L618F	Cholangiocarcinoma	Zoligratinib	Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Zoligratinib experienced treatment response.	33926920
GIMR	2021-04-06	FL	4	FGFR2	FGFR2-BICC1 fusion	Non-small cell lung cancer	Erdafitinib	Case report showing partial response to erdafitinib. Updated: 2022-02-16	35050756, 10.1200/PO.20.00110
GIMR	2021-07-06	FL	4	FGFR2	FGFR2-NRBF2 fusion, FGFR2-KIAA1217 fusion, FGFR2-CCDC170 fusion, FGFR2-AHCYL1 fusion, FGFR1-WDHD1 fusion, FGFR2-PAWR fusion, FGFR2-ATAD2 fusion, FTFR2-TRIM8 fusion	Cholangiocarcinoma	Pemigatinib	Exploratory analysis in patients with clinical benefits in the FIGHT-202 trial. 	33218975
GIMR	2024-09-25	FL	4	FGFR2	FGFR2-TTC28 fusion, FGFR2-OPTN fusion, K310R, V564F, V564L, M537I, N549D (N550D), N549K (N550K), N549H, V564I, E565A, L617V, K641N, K659M	Cholangiocarcinoma	Lirafugratinib	Preclinical study. RLY-4008, a highly selective FGFR2 inhibitor, showed activity across various FGFR2 alterations and resistance mutations, inducing regression in xenograft models with FGFR2 resistance mutations while sparing FGFR1 and FGFR4, suggesting broad therapeutic potential in FGFR2-driven cancers.	37270847
GIMR	2022-01-04	FL	4	FGFR2	Fusion	Solid tumours	Gunagratinib	Phase 1. ORR 33% in 12 patients including 1 CR (cholangiocarcinoma) and 3 PR. DCR 92%.	10.1200/JCO.2021.39.15_suppl.4092
GIMR	2021-12-15	FL	4	FGFR2	Fusion	Solid tumours	Lirafugratinib		10.1200/JCO.2021.39.15_suppl.TPS4165
GIMR	2023-01-23	FL	4	FGFR2	Fusion and E566G	Cholangiocarcinoma	Infigratinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2023-01-23	FL	4	FGFR2	Fusion and N549D (N550D), Fusion and N549K (N550K), Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642I, Fusion and K642R, Fusion and K660M	Cholangiocarcinoma	Futibatinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2023-01-23	FL	4	FGFR2	Fusion and N549D (N550D), Fusion and V563L, Fusion and V565I, Fusion and E566A, Fusion and E566G, Fusion and K642R	Cholangiocarcinoma	Erdafitinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2023-01-23	FL	4	FGFR2	Fusion and V563L, Fusion and E566A, Fusion and E566G, Fusion and K642R	Cholangiocarcinoma	Pemigatinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2020-09-25	FL	4	FGFR2	Fusions	Solid tumours	Futibatinib	FOENIX-101. ORR 11% in qd cohort	32622884
GIMR	2024-09-25	FL	4	FGFR2	K310R, M537I, K641N, K659M	Cholangiocarcinoma	Infigratinib		37270847
GIMR	2024-09-25	FL	4	FGFR2	K310R, M537I, N549D (N550D), N549K (N550K), N549H (N550H), V564I, E565A, L617V, K641N, K659M	Cholangiocarcinoma	Futibatinib		37270847
GIMR	2024-09-25	FL	4	FGFR2	K310R, M537I, N549H (N550H), V564I, E565A, L617V, K641N, K659M	Cholangiocarcinoma	Erdafitinib		37270847
GIMR	2024-09-25	FL	4	FGFR2	K310R, M537I, N549H (N550H), V564I, K641N, K659M	Cholangiocarcinoma	Pemigatinib		37270847
GIMR	2025-01-09	FL	4	FGFR2	K642I	Cholangiocarcinoma	Futibatinib; E7090	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-07-27	FL	4	FGFR2	K660M	Solid tumours	Erdafitinib, Pemigatinib		32973082
GIMR	2025-01-09	FL	4	FGFR2	K660N	Cholangiocarcinoma	Futibatinib; Pemigatinib; Erdafitinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-09-28	FL	4	FGFR2	L618F	Cholangiocarcinoma	Futibatinib		33926920
GIMR	2025-01-09	FL	4	FGFR2	N549H (N550H), N549K (N550K), E566A, E566G, L618M, L618V	Cholangiocarcinoma	Futibatinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-01-04	FL	4	FGFR2	N549H (N550H), V564I, K659N	Solid tumours	Gunagratinib	Cell line study. Ba/F3 cells harbouring both FGFR2-BICC1 fusion and secondary mutation remains sensitive to Gunagratinib.	10.1200/JCO.2021.39.15_suppl.4092
GIMR	2022-07-27	FL	4	FGFR2	N549H (N550H), V565I, V565L, E566G, K660M	Solid tumours	Futibatinib	In cell line studies, futibatinib is active several drug-resistant FGFR2 mutants including V565I gatekeeper mutants.	32973082
GIMR	2023-02-22	FL	4	FGFR2	N549K	Cholangiocarcinoma	E7090; Erdafitinib; Futibatinib		34272467
GIMR	2023-02-22	FL	4	FGFR2	N549K	Cholangiocarcinoma	E7090; Futibatinib		34272467
GIMR	2025-01-09	FL	4	FGFR2	N549K (N550K), N549D (N550D), K660M	Cholangiocarcinoma	Futibatinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2023-02-22	FL	4	FGFR2	N549S, N549H (N550H)	Cholangiocarcinoma	AZD4547; Infigratinib; E7090; Erdafitinib; Futibatinib; Pemigatinib		34272467
GIMR	2020-06-11	FL	4	FGFR2	Oncogenic mutations	Lung squamous cell carcinoma	Erdafitinib	Phase 2 trial (FIND)	10.1016/j.jtho.2018.08.628
GIMR	2021-02-02	FL	4	FGFR2	Overexpression	Urothelial carcinoma	Rogaratinib	Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation)	31405822
GIMR	2022-11-01	FL	4	FGFR2	Overexpression, FGFR2b Overexpression, FGFR2-IIIb Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Bemarituzumab + FOLFOX	Randomised phase 2. NCT03694522. N=155. The primary endpoint of median PFS showed a trend longer in the Bemarituzumab group versus placebo (9.5 vs 7.4 months) but did not reach the pre-specified threshold. FGFR overexpresspression was defined as IHC 2+/3+ in >0% of cells. Note in the exploratory analysis of FGFR2b overexpressed group in >= 10%, HR for PFS was 0.44; the OS of overall population was 0.58.	36244398
GIMR	2020-06-26	FL	4	FGFR2	Overexpression, FGFR2b Overexpression, FGFR2-IIIb Overexpression, Amplification	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Bemarituzumab	Phase 1. Confirmed partial response in 5/28 (18%) of patients with high FGFR2b-overexpressing gastric and gastroesophageal junction adenocarcinoma.	32167861
GIMR	2020-07-21	FL	4	FGFR2	S252W, N549K (N550K), C382R, Oncogenic mutations	Endometrial cancer	Dovitinib	ORR 4.5%. Did not meet prespecified threshold	25981814
GIMR	2024-11-22	FL	4	FGFR2	Truncating mutations, Rearrangements, FGFR2-E18, FGFR2-delE18, Exon 18 truncating mutations, FGFR2-BICC1 fusion, FGFR2-ATE1 fusion, FGFR2-E18-C2, FGFR2-E18-C3, FGFR2-E18-C4, Y674*, Y678*, L681fs*, P686*, S687fs*, S694*, C287R, Splice mutations, FGFR2-I17, FGFR2-E1-17AND Amplification	Solid tumours	AZD4547; Pemigatinib; Zoligratinib	Preclinical study. Truncated FGFR2 identified as actionable oncogene in multiple cancers, including rearrangements, partial amplifications, and nonsense/frameshift mutations, with FGFR2-E18 truncation being a single-driver alteration.	35948633
GIMR	2025-01-09	FL	4	FGFR2	V563L, E566A, E566G, K642R	Cholangiocarcinoma	Futibatinib; Pemigatinib; Erdafitinib; E7090	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2025-01-09	FL	4	FGFR2	V565I	Cholangiocarcinoma	Futibatinib; Erdafitinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-02-21	FL	4	FGFR3	Amplification	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In the FGFR amplification group (N=26), a single responder was seen in FGFR1 amplification (ORR 3.8%)	35176457
GIMR	2020-06-11	FL	4	FGFR3	Amplification, Fusion, Oncogenic mutations	Lung squamous cell carcinoma	Erdafitinib	Phase 2 trial (FIND)	10.1016/j.jtho.2018.08.628
GIMR	2020-06-11	FL	4	FGFR3	Amplification, Fusion, Oncogenic mutations and NOT V565 and NOT V550	Solid tumours	Erdafitinib	NCT01703481, Phase 1 dose escalation and expansion. ORR 46% in urothelial carcinoma and 27% in cholangiocarcinoma. <10% for the rest of tumour types.	31088831
GIMR	2021-03-08	FL	4	FGFR3	FGFR3-TACC3 fusion	Glioblastoma	Anlotinib	Case report	32949176
GIMR	2022-07-26	FL	4	FGFR3	FGFR3-TACC3 fusion, S249C	Solid tumours; Gastric cancer; Urothelial carcinoma	Futibatinib	NCT02052778. Phase 1 dose expansion. Overall, the ORR of the study was 14%. Responses were seen in one case of gastric cancer in FGFR3-TACC3 fusion and two cases of urothelial carcinoma harbouring S249C 	34551969
GIMR	2020-06-11	FL	4	FGFR3	Fusions	Solid tumours	AZD4547	Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.	10.1200/JCO.2018.36.15_suppl.2503
GIMR	2022-10-13	FL	4	FGFR3	Fusions, FGFR3-TACC3 fusion, V555M, V555L, V555G, V555K, K650M, K650E, Oncogenic mutations, S249C, R248C, Y373C, G370C	Solid tumours	TYRA-300	Preclinical study. TYRA-300 is a potent FGFR3-selective inhibitor targeting FGFR3 alterations in urothelial cancers and achondroplasia. It was designed to be effective against activating FGFR3 mutations and gatekeeper resistance mutations (V555L/M). Preclinical studies demonstrate significant FGFR3 isoform selectivity, potentially limiting toxicities observed with pan-FGFR inhibitors.	10.1016/j.annonc.2022.07.591, 32463741
GIMR	2020-04-16	FL	4	FGFR3	Fusions, S249C, A393E	Urothelial carcinoma	AZD4547	Isolated responses only in NCI-MATCH	32463741
GIMR	2022-10-20	FL	4	FGFR3	High mRNA expression and Oncogenic mutation; High mRNA expression and G370C; High mRNA expression and R248C; High mRNA expression and S249C; High mRNA expression and Y373C; High mRNA expression and FGFR3-TACC3 fusion	Urothelial carcinoma	Rogaratinib	NCT03410693. Randomised Phase 2. FORT-1. FGFR1/3 mRNA positive population. Post hoc exploratory analysis showed that in FGFR3 DNA alterations (oncogenic mutations and fusions, n=21) showed an ORR of 52% (11/21), compared to chemotherapy 27% (4/15).	36240478
GIMR	2023-02-22	FL	4	FGFR3	N540K, V555M, L608V	Cholangiocarcinoma	Ponatinib; Dovitinib	Preclinical study and case series. Polyclonal secondary FGFR2 mutations in the kinase domain were identified in cfDNA and biopsies of FGFR2 fusion-positive cholangiocarcinoma patients, driving acquired resistance to FGFR inhibitor BGJ398, and were surmountable by distinct FGFR inhibitors.	28034880
GIMR	2021-02-02	FL	4	FGFR3	Overexpression; High mRNA expression	Urothelial carcinoma	Rogaratinib	Phase 1 trial. mRNA overexpression (by Nanostring nCounter) used as trial eligibility. ORR 15% across FGFR1-3 group in the escalation cohort (10 of 15 patients without activating mutation)	31405822
GIMR	2022-02-21	FL	4	FGFR3	S249C	Solid tumours	Pemigatinib	Phase 1. FIGHT-101. In the FGFR mutation subgroup, ORR was 23% (3/13)	35176457
GIMR	2022-04-09	FL	4	FH	Oncogenic mutations	Papillary renal cell carcinoma	Cabozantinib + Nivolumab	Phase 2. NCT03635892. Single arm trial in non-clear cell renal cell carcinomas with ORR of 48%. Responses were seen in 10 of 12 patients with either NF2 or FH mutations. In exploratory biomarker analysis, FH mutation was associated with response with Cabozantinib and Nivolumab (5 of 6 cases).	35298296
GIMR	2022-11-02	FL	4	FLCN	Loss-of-function mutations	Renal cell carcinoma	Olaparib	Preclinical study. FLCN protein deficiency is associated with olaparib sensitivivty in cell line and xenograft models.	33069804
GIMR	2022-11-02	FL	4	FLCN	Loss-of-function mutations	Renal cell carcinoma	Sirolimus	Preclinical study. mTOR inhibitor, sirolimus, showed suppression of the tumour growth in Flcn-deficient allograft xenograft models.	26418749
GIMR	2020-09-21	FL	4	FLI1	EWSR1-FLI1 Fusion	Ewing sarcoma	TK216 + Vincristine	Phase 1 and 2: NCT02657005: ORR 7% (3/31 with 2 CR) and CBR 45% (14/31) in the dose expansion cohort at RP2D. mPFS 1.9 months.	10.1200/JCO.2021.39.15_suppl.11500, 10.1016/j.annonc.2020.08.1846
GIMR	2025-06-21	FL	4	FLT3	Internal tandem duplication	Acute myeloid leukaemia	Quizartinib	Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations.	38231480
GIMR	2025-06-21	FL	4	FLT3	Internal tandem duplication, D835Y, D835V, Y842C	Acute myeloid leukaemia	Gilteritinib	Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations.	38231480
GIMR	2025-06-21	FL	4	FLT3	Internal tandem duplication, F691L, D835Y, D835V, Y842C	Acute myeloid leukaemia	Foretinib	Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations.	38231480
GIMR	2020-06-13	FL	4	FOLR1	Overexpression	Ovarian cancer	Mirvetuximab soravtansine	FORWARD II	10.1200/JCO.2020.38.15_suppl.6004
GIMR	2025-06-09	FL	4	FOLR1	Protein expression	Ovarian cancer; Peritoneal serous carcinoma; Fallopian tube carcinoma	LY4170156	Phase 1a/b study. NCT06400472. LY4170156, an ADC targeting folate receptor alpha, showed a preliminary ORR of 38% (5/13) in HGSOC patients with varying FRα expression levels and prior mirvetuximab soravtansin treatment.	10.1200/JCO.2025.43.16_suppl.3023
GIMR	2022-06-04	FL	4	FOLR1	Protein expression	Solid tumours	MORAb-202	Phase 1. NCT03386942. Responses were seen in 10 of 22 across all dose levels. FR-alpha IHC was determined by any intensity in >= 5% of tumour cells.	33926914, 10.1200/JCO.2022.40.16_suppl.3090
GIMR	2020-10-05	FL	4	FRS2	Amplification	Liposarcoma	LY2874455		30795553
GIMR	2024-07-31	FL	4	Globo H	Expression	Solid Tumours	OBI-999	Phase 1. NCT04084366.	36701651
POTTR	2020-04-16	FL	4	GNA11	Oncogenic mutations	Solid tumours; Uveal melanoma	Crizotinib + Darovasertib; Binimetinib + Darovasertib	Preclinical study. Combination of PKC inhibitor IDE196 with MET inhibitor crizotinib synergistically inhibited tumor cell proliferation in uveal melanoma cells, overcoming HGF-induced resistance to IDE196.	10.1158/1538-7445.AM2021-1343
GIMR	2025-03-31	FL	4	GNA11	Oncogenic mutations	Uveal melanoma	Darovasertib	Phase 2 study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma, N=15, median tumor shrinkage was 11.2%/7.6%/22.7% after 1 month and 31.7%/11.9%/45.3% after 6 months.	10.1200/JCO.2024.42.16_suppl.9510
GIMR	2022-10-19	FL	4	GNA11	Oncogenic mutations	Uveal melanoma	DYP688	Phase 1 trial. NCT05415072. DYP688 is a first-in-class PMEL17-targeted antibody drug conjugate delivering a Gnaq/Gna11-specific inhibitor for metastatic uveal melanoma. It demonstrates potent antiproliferative activity and induces apoptosis in PMEL17-positive, GNAQ/11-mutant UVM cells.	10.1158/1538-8514.CANCERCHEM24-IA022
POTTR	2020-04-16	FL	4	GNAQ	Oncogenic mutations	Solid tumours; Uveal melanoma	Crizotinib + Darovasertib; Binimetinib + Darovasertib	Preclinical study. Combination of PKC inhibitor IDE196 with MET inhibitor crizotinib synergistically inhibited tumor cell proliferation in uveal melanoma cells, overcoming HGF-induced resistance to IDE196.	10.1158/1538-7445.AM2021-1343
GIMR	2025-03-31	FL	4	GNAQ	Oncogenic mutations	Uveal melanoma	Darovasertib	Phase 2 study of neoadjuvant/adjuvant darovasertib for localized ocular melanoma, N=15, median tumor shrinkage was 11.2%/7.6%/22.7% after 1 month and 31.7%/11.9%/45.3% after 6 months.	10.1200/JCO.2024.42.16_suppl.9510
GIMR	2022-10-19	FL	4	GNAQ	Oncogenic mutations	Uveal melanoma	DYP688	Phase 1 trial. NCT05415072. DYP688 is a first-in-class PMEL17-targeted antibody drug conjugate delivering a Gnaq/Gna11-specific inhibitor for metastatic uveal melanoma. It demonstrates potent antiproliferative activity and induces apoptosis in PMEL17-positive, GNAQ/11-mutant UVM cells.	10.1158/1538-8514.CANCERCHEM24-IA022
GIMR	2023-12-14	FL/BZ	4	GNAS	R201C, R201H	Non-small cell lung cancer	Trametinib	Case report. A NSCLC patient with osimertinib resistance harboring GNAS R201C and R201H mutations showed stable disease when treated with trametinib.	35946511
GIMR	2023-12-14	FL/BZ	4	GNAS	R201H	Appendiceal cancer	Trametinib	Case report. A patient with appendiceal adenocarcinoma and a GNAS R201H mutation experienced clinical benefit from trametinib, with a decrease in tumor markers and improvement in quality of life.	28868010
GIMR	2025-02-14	FL	4	GPC3	Protein expression	Hepatocellular carcinoma	BGB-B2033	Preclinical study. BGB-B2033, a 4-1BB/GPC3 bispecific antibody, exhibits potent antitumor activity in GPC3-expressing tumor models.	10.1158/1538-7445.AM2025-6009
GIMR	2025-02-14	FL	4	GPC3	Protein expression	Hepatocellular carcinoma	BOS-342		ACTRN12623000798662
GIMR	2025-02-14	FL	4	GPC3	Protein expression	Hepatocellular carcinoma	MT-303	Preclinical study. MT-303, an LNP-formulated GPC3-specific CAR mRNA, demonstrated improved expression and anti-tumor activity in a hepatocellular carcinoma xenograft model (HepG2). 	10.1136/jitc-2024-SITC2024.1125
GIMR	2023-07-24	FL	4	H3F3A	G34R, G34V	Diffuse hemispheric glioma	Pamiparib + AZD7762	Preclinical study. Syngeneic pediatric HCC cells harbouring H3.3-G34R mutation showed downregulation of DNA repair pathways, and inhibition of the DDR resulted in accumulation of extrachromosomal DNA and cGAS/STING pathway activation. In mouse models, pamiparib and AZD7762 resulted in long-term survival for approximately 50% of the mice. STING agonist (diABZl) enhanced long-term survivors developing immunological memory.	36125896
GIMR	2025-04-23	FL	4	H3F3A	G34R, G34V	Diffuse hemispheric glioma	Ribociclib; BSJ-03-123	Preclinical study and case report. CDK6 is a targetable vulnerability in diffuse hemispheric glioma (H3G34-mutant), with tumor cells demonstrating sensitivity to Ribociclib and a CDK6-specific degrader. This approach promotes more mature interneuron-like states and reduces tumor growth. In a 10-year-old patient, third-line treatment with ribociclib induced disease control for 17 months.	39232581
GIMR	2023-08-30	FL	4	H3F3A	K27M, K28M	Diffuse midline glioma	ONC201 + Paxalisib	Case reports. ONC201 + Paxalisib in two DIPG patients with H3.1K27M and H3.3K27M altered midline glioma.]	37145169
GIMR	2023-08-30	FL	4	H3F3A	K27M, K28M	Diffuse midline glioma	ONC201 + Paxalisib	Case reports. ONC201 + Paxalisib in two DIPG patients with H3.1K27M and H3.3K27M altered midline glioma.]	37145169
GIMR	2021-07-06	FL	4	H3F3A	K27M, K28M	High-grade gliomas; Diffuse intrinsic pontine glioma; H3K27M-mutant glioma	GSK343; EPZ6438	EZH2 activities is required for growth of DIPG cells in cell line models of pediatric gliomas. All H3K27M cell lines were sensitive to EZH2 inhibition. The inhibition of EZH2 is dependent on function of p16INK4A.	28263309
GIMR	2022-01-28	FL	4	HLA-A+PMEL	HLA-A:A*02:01 and PMEL:Protein expression	Melanoma; Uveal melanoma	Tebentafusp	Phase 1. NCT01211262. OS rate at 12 months was 65% in both uveal melanoma and previously treated cutaneous melanoma. Gp100 is lineage-specific for melanocyte and melanoma cells.	32816891
GIMR	2025-02-24	FL	4	HLA-A2+PRAME	HLA-A2:A*02:01 AND PRAME:Protein expression	Melanoma	IMC-F106C	Phase 1 trial. NCT04262466. In 31 evaluable patients, IMC-F106C, a bispecific PRAME x CD3 ImmTAC showed activity in post-checkpoint cutaneous melanoma patients with 61% CBR and 13% ORR, enriched in PRAME-positive patients (immunohistochemistry H score>1).	10.1200/JCO.2024.42.16_suppl.9507
GIMR	2020-04-16	FL	4	Homologous Recombination Deficiency Score	High	Breast cancer	Cisplatin	Preclinical and clinical study. Homologous recombination deficiency (HRD) score, defined as HRD score ≥42 or BRCA1/2 mutation, predicts response to platinum-containing neoadjuvant chemotherapy in triple-negative breast cancer patients, including those with BRCA1/2 nonmutated tumors with high HRD scores.	26957554
GIMR	2023-02-22	FL	4	Homologous Recombination Deficiency Score	High	Endometrial cancer; Uterine serous carcinoma	Cisplatin; Olaparib	Cell line studies suggest that models with high HRD score have higher sensitive to cisplatin and olaparib.	33563487
GIMR	2026-02-02	FL	4	Homologous Recombination Deficiency Score	High	Prostate cancer; Ovarian cancer	PARP inhibitor	Pan-cancer analysis of 260,333 samples identified 10 copy-number signatures associated with diverse processes, and a novel HRDsig that outperformed gLOH in predicting BRCAness. The PARPi benefit in was seen in clinicogenomic ovarian and prostate cancers.	37769224
GIMR	2021-06-21	FL	4	HPV genotype	HPV16-positive	HPV16-positive cancers	HB-201; HB-201 + HB-202	Phase 1/2 study. NCT04180215. HB-201 monotherapy demonstrated preliminary antitumor activity in 16 HPV16+ cancer patients (predominantly HNSCC) with 2 partial responses and 6 stable disease outcomes. Alternating HB-201 and HB-202 therapy achieved stable disease in 2 of 2 patients.	10.1200/JCO.2021.39.15_suppl.2502
GIMR	2024-02-26	FL	4	HRAS	G12C	Solid tumour	Sotorasib; JQD443; RM-018	Preclinical study. Sotorasib is a potent NRASG12C inhibitor, more potent than KRASG12C (5-fold) in vitro. In addition, sotorasib is also a HRASG12C inhibitor. This was demonstrated by the clinical response of a patient with NRASG12C colorectal cancer treated with sotorasib and panitumumab.	38236605
GIMR	2025-06-10	FL	4	HRAS	G12D	Breast cancer	ADT-007	Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells.	39700396
POTTR	2020-04-16	FL	4	HRAS	Oncogenic mutations	Solid tumours	Selumetinib; Cobimetinib; PD0325901	Preclinical study. Mutant HRAS cancer cell lines showed sensitivity to MEK inhibitors (AZD6244, MEK162, and PD0325901) and mTOR inhibition, with synergistic effects observed with combined MEK and mTOR inhibition, suggesting a potential therapeutic target for HRAS mutant tumors.	26544513
POTTR	2020-04-16	FL	4	HRAS	Oncogenic mutations	Solid tumours	Ulixertinib; LY3214996; LTT462; Ravoxertinib	ERK inhibitors	29431672, 29247021, 10.1200/JCO.2019.37.15_suppl.3001
GIMR	2025-06-11	FL	4	HRAS	Oncogenic mutations, Q95H	Solid tumours	BI-2493; BI-2865	Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models.	37258666
GIMR	2023-03-29	FL	4	Human Papillomavirus Status	Negative	Head and neck squamous cell carcinoma	Ficlatuzumab + Cetuximab	NCT03422536. In treatment refractory HPV-negative HNSCC, patients in the Ficlatuzumab + Cetuximab combination arm resulted in ORR of 38% (6/16) with median PFS of 4.1 months.	36977289
GIMR	2024-01-22	FL	4	IDH1	Oncogenic mutation	Acute myeloid leukaemia	Olaparib; Talazoparib	In vitro study. Increased DNA damage and sensitization to daunorubicin, ionizing radiation, and PARP inhibitors were observed in IDH1/2MUT AML cells. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells.	29339439
GIMR	2020-12-31	FL	4	IDH1	R132	Chondrosarcoma	Ivosidenib	Phase 1 trial. Treatment with ivosidenib resulted in no objective response, but with a CBR 52% and associated reduction of 2HG level.	32208957
GIMR	2020-05-30	FL	4	IDH1	R132	Glioma	Olutasidenib	Phase Ib/II trial. Olutasidenib demonstrated preliminary clinical activity in patients with relapsed/refractory IDH1-mutant glioma, with 8% achieving partial response and 32% having stable disease, in those harbouring IDH1 R132 mutations.	35639513, 10.1200/JCO.2020.38.15_suppl.2505
GIMR	2020-06-25	FL	4	IDH1	R132	Glioma; Glioblastoma	Ivosidenib	Phase 1 trial. PFS 13.6 month non-enhancing. ORR 2%	32530764
GIMR	2023-11-20	FL	4	IDH1	R132	High-grade gliomas	PRT811	Phase 1 dose-expansion trial. NCT04089449. In IDH1/2-mutated glioma (n=16), PRT811 treatment was associated with 2 CR (1 durable) and 1 unconfirmed PR.	10.1200/JCO.2023.41.16_suppl.3008
GIMR	2025-06-09	FL	4	IDH1	R132	Low-grade glioma	BAY1436032	Phase I trial. NCT02746081. BAY1436032 showed clinical activity in a subset of heavily pretreated subjects with lower grade glioma (LGG), with an objective response rate of 11% and stable disease in 43%, and a 3-month PFS rate of 0.31, while no objective responses were observed in glioblastoma, intrahepatic cholangiocarcinoma, or other tumor types.	33622704
GIMR	2022-11-01	FL	4	IDH1	R132, R132C, R132L, R132G	Cholangiocarcinoma	Ivosidenib; Olutasidenib; Vorasidenib	Multicentre retrospective series. Median PFS was 4.6 months with DCR 29% in 15 (23%) patients treated with IDH inhibitors.	35005992
GIMR	2023-03-08	FL	4	IDH1	R132C, R132	Chondrosarcoma; Epithelioid hemangioendothelioma	Olaparib	OLAPCO. Clinical benefit observed in 3 of 5 chondrosarcomas (1 PR and 2 SD). One prolonged SD in pulmonary epithelioid hemangioendothelioma.	34994649
GIMR	2021-03-19	FL	4	IDH1	R132C, R132H, R132	Solid tumours; Glioma; Glioblastoma; Cholangiocarcinoma	Olaparib; Veliparib	Cell line study. Mutant IDH cells were demonstrated to be deficient in DNA DSB break repair.	28148839, 32494639
GIMR	2023-08-23	FL	4	IDH1	R132C+D279N	Cholangiocarcinoma	LY3410738	Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib related to the treatment-emergent D279N mutation showed sensitivity to LY3410738.	36056177
GIMR	2020-05-30	FL	4	IDH1	R132H	Glioma	Vorasidenib		10.1200/JCO.2020.38.15_suppl.2504
GIMR	2021-10-06	FL	4	IDH1	R132H, R132C, R132G, R132L, R132S, R132	Low-grade gliomas; Solid tumours	Vorasidenib	Phase 1. NCT02481154. ORR in non-enhancing gliomas was 4/22 (18%). In enhancing gliomas, ORR was 0/30 (0%). In solid tumours, 1/41 responders (2.4%) with median PFS of 1.9 months.	34078652
GIMR	2024-01-22	FL	4	IDH2	Oncogenic mutation	Acute myeloid leukaemia	Olaparib; Talazoparib	In vitro study. Increased DNA damage and sensitization to daunorubicin, ionizing radiation, and PARP inhibitors were observed in IDH1/2MUT AML cells. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells.	29339439
GIMR	2020-05-30	FL	4	IDH2	R140Q	Glioma	Vorasidenib		10.1200/JCO.2020.38.15_suppl.2504
GIMR	2020-06-15	FL	4	IDH2	R140Q	Liquid cancers	Enasidenib		28193778
GIMR	2021-10-06	FL	4	IDH2	R140Q, R172K, R172	Low-grade gliomas; Solid tumours	Vorasidenib	Phase 1. NCT02481154. ORR in non-enhancing gliomas was 4/22 (18%). In enhancing gliomas, ORR was 0/30 (0%). In solid tumours, 1/41 responders (2.4%) with median PFS of 1.9 months.	34078652
GIMR	2022-11-01	FL	4	IDH2	R172, R172M, R172K, R172G, R172W, R172T	Cholangiocarcinoma	Enasidenib	Multicentre retrospective series. Median PFS was 4.6 months with DCR 29% in 15 (23%) patients treated with IDH inhibitors.	35005992
GIMR	2021-03-19	FL	4	IDH2	R172K	Solid tumours; Glioma; Glioblastoma; Cholangiocarcinoma	Olaparib; Veliparib	Cell line study. Mutant IDH cells were demonstrated to be deficient in DNA DSB break repair.	28148839, 32494639
GIMR	2023-03-08	FL	4	IDH2	R172K, R172	Chondrosarcoma; Epithelioid hemangioendothelioma	Olaparib	OLAPCO. Clinical benefit observed in 3 of 5 chondrosarcomas (1 PR and 2 SD). One prolonged SD in pulmonary epithelioid hemangioendothelioma.	34994649
GIMR	2021-03-31	FL	4	Intrinsic subtype	Luminal A; Luminal B; HER2-enriched; Normal-like	Breast cancer	Ribociclib + Tamoxifen; Ribociclib + Fulvestrant; Ribociclib + Letrozole; Ribociclib + Anastrozole	Exploratory analysis from MONALEESA-7, -3, 2 using intrinsic subtype 152 gene expression panel for classification into PAM50-subtypes. Higher ORR was seen in HER2E and LumB subtypes, and PFS benefit was seen in all except Basal subtypes (LumA, LumB, HER2E, and Normal subtypes).	33769862
GIMR	2022-04-13	FL	4	IRS2	Amplification	Colorectal adenocarcinoma	BMS-754807	Cell lines with wild-type KRAS/BRAF were sensitive to BMS-754807 (in the presence of high IR-A RNA expression or low IGFBP6 levels)	25527633
GIMR	2022-04-13	FL	4	IRS2	Amplification, Protein expression	Small-cell lung cancer	Ceritinib	Xenograft model study showing inhibition of cell growth by Ceritinib in IRS2-amplified/expressing PDX-derived cells.	32099898
GIMR	2021-08-19	FL	4	JAK2	PCM1-JAK2 fusion	Acute lymphoblastic leukaemia	Ruxolitinib	Case report	33502001
GIMR	2021-08-19	FL	4	JAK2	PCM1-JAK2 fusion	Chronic eosinophilic leukaemia	Ruxolitinib	Case report. Complete cytogenetic response	22899477
GIMR	2022-08-30	FL	4	KAT6A	Amplification, Overexpression	Breast cancer	PF-9363		10.1158/1538-7445.AM2021-1130
GIMR	2025-03-15	FL	4	KAT6A	Amplification, Overexpression	Breast cancer	PF-9363	Preclinical study. The selective KAT6A/KAT6B inhibitor demonstrated anti-tumor activity and growth suppression in KAT6-high ER+/luminal breast cancer models with or without ESR1 mutations associated with endocrine resistance.	37557181
GIMR	2021-09-22	FL	4	KDM6A	Loss-of-function mutations	Multiple myeloma	GSK343	Loss of UTX enhances sensitizes multiple myeloma cells to EZH2 inhibition	29045832
GIMR	2022-02-23	FL	4	KDM6A	Oncogenic mutations, Loss-of-function mutations	Pancreatic adenocarcinoma	JQ1	Cell line study. KDM6A-deficient PDAC is sensitive to BET inhibitors and reversed squamous differentiation.	29533787
GIMR	2022-02-23	FL	4	KDM6A	Oncogenic mutations, Loss-of-function mutations	Pancreatic adenocarcinoma	Vorinostat; Trichostatin A; Valproic acid	Cell line study. Showing KDM6A sensitive cells are sensitive to HDAC inhibition	30556125
GIMR	2022-03-04	FL	4	KEAP1	Oncogenic mutations	Non-small cell lung cancer	Talazoparib	Preclinical study. Loss of KEAP1 induces a BRCAness phenotype in KEAP1-mutant lung cancer, mediated by stabilisation of EMSY, leading to sensitisation of PARP inhibitor.	34963055
GIMR	2021-06-10	FL	4	KEAP1+KRAS	KRAS:G12C AND NOT KEAP1:Oncogenic mutations	Non-small cell lung cancer	Sotorasib	Higher ORR (44%) was identified in patients with KEAP oncogenic mutations treated with Sotorasib in the CodeBreak100 trial.	34096690, 10.1200/JCO.2021.39.15_suppl.9003
GIMR	2025-07-07	FL	4	KIT	A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K  	Gastrointestinal stromal tumour	IDRX-42	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	4	KIT	A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K  	Gastrointestinal stromal tumour	NB003	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	4	KIT	A502_Y503dup, Exon11 deletion, K642E, V654A, D816A, D820A, N822K, A829P, A502_Y503dup and N822K  	Gastrointestinal stromal tumour	Ripretinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	4	KIT	A502_Y503dup, Exon11 deletion, K642E, V654A, T670I, D820A, N822K, A829P, V654A and D820A, V654A and N822K, V654A and A829P  	Gastrointestinal stromal tumour	Nintedanib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	4	KIT	A502_Y503dup, Exon11 deletion, K642E, V654A, T670I, V654A and D820A  	Gastrointestinal stromal tumour	Sunitinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	4	KIT	A502_Y503dup, Exon11 deletion, V654A, D816A, D820A, N822K, A829P, V654A and D820A, V654A and N822K, V654A and A829P, D842V  	Gastrointestinal stromal tumour	Avapritinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2021-07-08	FL	4	KIT	Amplification	Glioblastoma	Imatinib + Hydroxyurea	Negative phase 2 study in GBM patients with ORR of 3.5% and CBR of 23% in unselected population. Note: exploratory biomarker analysis identified a single case -KIT amplification was identified by FISH had SD for 9.7 months (overall cohort PFS 5.6 months). KIT copy number not quantified.	19904263
GIMR	2020-04-23	FL	4	KIT	D816V	Gastrointestinal stromal tumour	Avapritinib; Crenolanib; Midostaurin	Preclinical studies and case reports. Type II c-Kit inhibitors are resistant to KIT D816 and PDGFR842V mutations	29093181
GIMR	2021-08-13	FL	4	KIT	D816V	Mastocytosis	Cabozantinib	Single case report of telangectasia macularis eruptiva perstans that harbours KIT D816V with clinical response.	10.1016/j.jaad.2014.01.550
GIMR	2020-06-18	FL	4	KIT	D816V, T670A, T670V	Solid tumours	Midostaurin	Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation.	31270078
GIMR	2020-06-18	FL	4	KIT	D816V, V654A, N655K, Y672C, D677N, T670A	Solid tumours	Avapritinib	Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation.	31270078
GIMR	2021-12-17	FL	4	KIT	D820E	Thymic carcinoma	Sorafenib	Case report. PR 15 months	19461405
GIMR	2020-04-23	FL	4	KIT	Exon 11 mutation	Gastrointestinal stromal tumour	Avapritinib; Imatinib; Sunitinib; Regorafenib; Crenolanib; Midostaurin	Preclinical studies and case reports.	29093181
GIMR	2022-07-27	FL	4	KIT	Exon 11 mutation, Exon 11 deletion	Thymic carcinoma	Sorafenib	Case report. A relapsed thymic carcinoma patient with C-KIT exon 11 deletion mutation showed positive response to sorafenib.	20970876
GIMR	2023-06-27	FL	4	KIT	Exon 11 mutation, Exon 11 deletion, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829P	Gastrointestinal stromal tumour	Bezuclastinib	Phase 1b/2a trial. NCT02401815. N=39. Combination of type I KIT inhibitor PLX9486 and type II KIT inhibitor sunitinib showed clinical benefit in patients with refractory GIST, with median PFS of 12.1 months and clinical benefit rate of 80% at the recommended phase 2 dose.	34236401
GIMR	2022-07-27	FL	4	KIT	Exon 11 mutation, Exon 11 deletion, V560del	Thymic carcinoma	Imatinib	Case report. Thymic carcinoma with overexpressed mutated KIT showed response to imatinib.	15201427
GIMR	2022-07-27	FL	4	KIT	Exon 11 mutation, Y553N	Thymic carcinoma	Imatinib	Case report. A heavily pretreated patient with metastatic c-KIT mutated thymic carcinoma showed an impressive response to imatinib.	21969494
GIMR	2022-07-27	FL	4	KIT	Exon 17 mutation, D820E	Thymic carcinoma	Sorafenib	Case report. A heavily pretreated patient with metastatic thymic carcinoma responded to sorafenib, with a c-kit missense mutation (D820E) on exon 17 potentially explaining the clinical response.	19461405
GIMR	2021-08-13	FL	4	KIT	Exon 9 mutations, A502_Y503dup, Exon 11 mutations, Exon 11 deletion, K558_G565delinsR, Exon 17 mutations, D820G, V559A, V559D, V560G, K642E, D816E, D816F, D816H, D816I, D816V, D816Y, D820E, D820Y, Y823D, A829P	Gastrointestinal stromal tumour	Cabozantinib	Drug sensitivity screening in GIST xenografts with different KIT mutations	27777285
GIMR	2025-07-07	FL	4	KIT	Exon11 deletion  	Gastrointestinal stromal tumour	Imatinib; Regorafenib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	4	KIT	Exon11 deletion, D820A, A829P  	Gastrointestinal stromal tumour	Bezuclastinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2020-06-27	FL	4	KIT	L576P, V669D, V559A, V559G, T670I, V654A, N822K, A829P	Gastrointestinal stromal tumour	Axitinib	Preclinical study. Axitinib showed potent activity against various cKIT primary and secondary mutations, including imatinib-resistant T670I and V654A mutants, in GIST preclinical models and patient-derived primary cells.	31205508
GIMR	2020-04-16	FL	4	KIT	Oncogenic mutations	Thymic carcinoma	Imatinib; Sunitinib	Case report. A patient with c-kit mutation-positive thymic carcinoma achieved long-term disease control (~27 months) with consecutive treatment of imatinib and sunitinib, demonstrating the efficacy of molecular-targeted therapy for thymic carcinoma with oncogenic driver mutations.	27073655
GIMR	2020-04-16	FL	4	KIT	Oncogenic mutations	Thymic carcinoma	Sunitinib	Retrospective analysis of French RYTHMIC network database. N=28. Sunitinib in previously-treated thymic epithelial tumors with disease control rate 63%, ORR 22%, median PFS 3.7 months, and median OS 15.4 months. Among 8 sequenced patients, 1 PR and 2 PD observed, exon 11 c-Kit mutation and achieved PFS 5.5 months and OS 7.5 months.	27237035
GIMR	2020-04-23	FL	4	KIT	Oncogenic mutations, Exon 11 mutation, Exon 9 mutation, D816E, D816F, D816I, D816V, D816Y, V560G, V559D, D820E, Y823D, D820Y, D557	Gastrointestinal stromal tumour	Avapritinib	Preclinical studies and case reports. BLU-285 Responses seen in KIT D820Y mutation treated with showed a 25% tumor shrinkage, and a patient with advanced SM treated with BLU-285 showed a marked decrease in bone marrow mast cells, indicating early antitumor activity.	29093181
GIMR	2020-12-31	FL	4	KIT	Overexpression	Adenoid cystic carcinoma	Imatinib	Mixed results in one case series (one responder of 8).	16135502
POTTR	2020-04-16	FL	4	KIT	Overexpression	Solid tumours	LOP628	Preclinical study. c-KIT-directed antibody-drug conjugate LOP628 exhibited potent antiproliferative activity against c-KIT-positive cell lines and demonstrated regressions or stasis in GIST and SCLC xenograft models, including an imatinib-resistant GIST model.	29764854
GIMR	2022-07-27	FL	4	KIT	Overexpression	Thymic neuroendocrine carcinoma	Imatinib	Case series. Responses to imatinib seen In two CD117 positive atypical thymic carcinoid. No KIT mutations in both cases.	20876428
GIMR	2021-12-17	FL	4	KIT	P577_Y579del	Thymic carcinoma	Sorafenib	Case report. SD for at least 6 months with metabolic response on FDG-PET.	20970876
GIMR	2021-07-01	FL	4	KIT	Protein expression	Adenoid cystic carcinoma	Imatinib	Case reports of response 	15350030
GIMR	2021-08-13	FL	4	KIT	V559G, T670I, V654A, D816E, D820E, D820G, D820Y, N822K, A829P, V560_Y578del, K624E	Gastrointestinal stromal tumour	Cabozantinib	Drug sensitivity screen.	21926191
GIMR	2022-01-25	FL	4	KIT	V560D, A502_Y503dup, V654A, T670I, D820A, D820E, D820G, D820Y, N822H, N822K, Y823D, A829P	Gastrointestinal stromal tumour	Sorafenib	Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842.	22665524
GIMR	2021-12-17	FL	4	KIT	Y553N	Thymic carcinoma	Imatinib	Case report. PR 8 months	21969494
GIMR	2020-11-23	FL	4	KMT2C	Loss-of-function mutations, Deletion	Urothelial carcinoma	Olaparib	Cell-line study suggesting that KMT2C loss may results in HRD-like defects and sensitive to olaparib	30665945
GIMR	2020-09-15	FL	4	KRAS	Amplification and NOT missense variant	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Trametinib + SHP099		29808010
GIMR	2020-11-10	FL	4	KRAS	G12	Solid tumours	Avutometinib	Phase 1 dose-escalation and basket dose-expansion study. NCT02407509. Avutometinib, a RAF-MEK inhibitor, demonstrated antitumour activity in RAS/RAF-mutant solid tumours and multiple myeloma, with 7 (27%) of 26 response-evaluable patients achieving objective responses at the recommended phase 2 dose of 4.0 mg twice per week.	33128873
GIMR	2020-11-03	FL	4	KRAS	G12, Amplification	Solid tumours	Vociprotafib + Cobimetinib	Phase 1.	10.1016/S0959-8049(20)31089-3
GIMR	2025-05-24	FL	4	KRAS	G12, G12D, G12V, G12C, G12A, G12S	Non-small cell lung cancer; Pancreatic adenocarcinoma; Colorectal adenocarcinoma	RMC-6236	Preclinical study. RMC-6236, a RAS(ON) multi-selective noncovalent inhibitor, demonstrated anticancer activity across RAS-addicted cell lines and induced tumor regressions in KRASG12X xenograft models. In a phase I/Ib clinical trial (NCT05379985), the inhibitor showed initial activity with objective responses in patients with advanced KRASG12X lung and pancreatic adenocarcinoma.	38593348
GIMR	2023-10-30	FL	4	KRAS	G12, G12D, G12V, G12R, G12D, G12V, G12A	Pancreatic adenocarcinoma; Non-small cell lung cancer	RMC-6236	Phase 1 trial. NCT04896732. N=33. in patients with KRASG12X, preliminary anti-tumor activity was seen with RMC-6236 pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Objective response rate was 36% (2 / 10  confirmed, 3 / 4 unconfirmed), median time to onset of initial response was 6 weeks, disease control rate was 86.	10.1016/j.annonc.2023.09.1838
GIMR	2023-05-05	FL	4	KRAS	G12A	Endometrial cancer	Lifirafenib + Mirdametinib	Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. 	10.1158/1538-7445.AM2023-CT033
GIMR	2020-05-30	FL	4	KRAS	G12C	Colorectal adenocarcinoma	Sotorasib	CODEBREAK 100. ORR 7%	32955176, 10.1200/JCO.2020.38.15_suppl.4018
GIMR	2023-05-05	FL	4	KRAS	G12C	Colorectal cancer; Pancreatic adenocarcinoma; Solid tumours	LY3537982	Phase 1. NCT04956640. ORR was 7% (1/17) in CRC,  3/8 (38%) in pancreatic, and 4/15 (36%) in other solid tumorus.	10.1158/1538-7445.AM2023-CT028
GIMR	2025-05-04	FL	4	KRAS	G12C	Non-small cell lung cancer	D3S-001	Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and  clinical efficacy.	38717075
GIMR	2023-05-05	FL	4	KRAS	G12C	Non-small cell lung cancer	LY3537982	Phase 1. NCT04956640. ORR 3/5 (60%) in KRAS G12C inhibitor treatment naive NSCLC.	10.1158/1538-7445.AM2023-CT028
GIMR	2022-06-04	FL	4	KRAS	G12C	Non-small cell lung cancer; Colorectal adenocarcinoma	JAB-21822	Phase 1. NCT05009329.	10.1200/JCO.2022.40.16_suppl.3089
GIMR	2025-04-28	FL	4	KRAS	G12C	Solid tumours	BBO-8520	Preclinical study. BBO-8520 is a covalent inhibitor that targets both GTP(ON) and GDP(OFF)-bound KRASG12C, achieving potent signaling inhibition in growth factor-activated states, efficient target engagement, and durable tumor regression across multiple models, including those resistant to KRASG12C(OFF)-only inhibitors.	39642212
GIMR	2022-05-03	FL	4	KRAS	G12C	Solid tumours	LY3537982		10.1158/1538-7445.AM2021-1259
GIMR	2024-06-09	FL	4	KRAS	G12C	Solid tumours	Olomorasib	Phase 1/2 LOXO-RAS-20001. N=157. Olomorasib showed activity across KRAS G12C-mutant solid tumours. ORR was 9% in CRC and 40% in non-CRC tumors. with median PFS of 4-9 months.	10.1200/JCO.2024.42.16_suppl.3007
GIMR	2022-02-04	FL	4	KRAS	G12C	Solid tumours	RMC-4550	Cell line study.	30104724
GIMR	2020-04-16	FL	4	KRAS	G12C	Solid tumours	Sotorasib	CODEBREAK 100. PR in pancreatic, endometrial, melanoma, appendiceal cancers	32955176, 10.1200/JCO.2020.38.15_suppl.3511, 10.1200/JCO.2020.38.15_suppl.TPS3661
GIMR	2025-06-12	FL	4	KRAS	G12C	Solid tumours	VVD-442	Preclinical study. Covalent binding to C242 in the PI3K p110 alpha RBD inhibits RAS-PI3K interaction, suppressing growth of RAS mutant and HER2 over-expressing tumors without inducing hyperglycemia.	10.1101/2024.12.17.629001
GIMR	2022-02-22	FL	4	KRAS	G12C	Solid tumours except non-small cell lung cancer	Adagrasib	Phase 1/1B. KRYSTAL-1. In a total of 7 cases (4 colorectal, 2 appendiceal, 1 duodenal adenocarcinomas) at various dosing levels, 1 (of 4) colorectal achieved an objective response.	35167329
GIMR	2025-03-16	FL	4	KRAS	G12C	Solid tumours; Non-small cell lung cancer	Sotorasib + Tipifarnib	Preclinical study. Tipifarnib and sotorasib combination showed synergistic anticancer effects in lung adenocarcinoma cells by inhibiting proliferation and interfering with HRAS activation and RHEB/lamin farnesylation.	38278976
GIMR	2022-08-12	FL	4	KRAS	G12C, G12A, G12S, G12	Solid tumours	SHP099 + Trametinib	Cell line study. TNBC and RAS G12 tumours are known to be sensitive to combined SHP2-MEK inhibition in cell line models.	30605687
GIMR	2025-06-10	FL	4	KRAS	G12C, G12D, G12S, G12V, G13D, P121H, Amplification	Solid tumours; Pancreatic adenocarcinoma; Lung adenocarcinoma; Colon adenocarcinoma; Breast adenocarcinoma; Low-grade serous ovarian cancer; Melanoma; Gastric cancer	ADT-007	Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells.	39700396
GIMR	2023-05-05	FL	4	KRAS	G12D	Appendiceal cancer	BGB-3245	Phase 1. NCT04249843. Response seen in a patient with appendiceal cancer harbouring KRAS G12D mutation.	10.1158/1538-7445.AM2023-CT031
GIMR	2026-03-11	FL	4	KRAS	G12D	Colorectal adenocarcinoma	BBO-11818 + Cetuximab	Preclinical study. BBO-11818. Potent noncovalent pan-KRAS inhibitor targeting ON and OFF states of KRAS G12D, G12V, and G12C. Potently inhibited MAPK signaling and cellular viability in KRAS-driven cell lines. Produced tumor regressions in KRAS-mutant xenograft models. Enhanced efficacy observed in combination with anti-PD-1, anti-EGFR antibodies, and RAS:PI3Kα breaker.	41790032
GIMR	2022-12-07	FL	4	KRAS	G12D	Pancreatic adenocarcinoma; Colorectal adenocarcinoma	MRTX1133		36472553
GIMR	2024-09-23	FL	4	KRAS	G12D	Pancreatic adenocarcinoma; Non-small cell lung cancer	RMC-9805	Preclinical study. RMC-9805, a mutant-selective covalent oral KRASG12D inhibitor, induced apoptosis and tumor regression in KRASG12D models, with objective responses seen in pancreatic and non-small cell lung cancer PDX and CDX models.	10.1158/1538-7445.AM2023-526
GIMR	2023-10-30	FL	4	KRAS	G12D	Solid tumour	HRS-4642	Phase 1 trial. NCT05597436. N=18. One NSCLC patient at 200 mg had PR, and 11/18 pts (61.1%) had SD with 33.3% experienced target lesion shrinkage	10.1016/j.annonc.2023.10.025
GIMR	2022-01-27	FL	4	KRAS	G12D	Solid tumours	MRTX1133	Discovery of the KRAS G12D inhibitor MRTX1133 showing reduction in volume in a pancreatic cancer xenograft mouse model.	34889605
GIMR	2025-04-27	FL	4	KRAS	G12D	Solid tumours; Non-small cell lung cancer	HRS-4642	Phase 1 trial. NCT05533463. HRS-4642 demonstrated anti-tumor activity against KRAS G12D-mutant cancers in vitro, in vivo, and dose escalation studies, with 2/9 responders in NSCLC.	38942026
GIMR	2026-03-11	FL	4	KRAS	G12D, G12V, G12C, G12A, G12S, G13D, Amplification and NOT Oncogenic mutation	Solid tumours	BBO-11818	Preclinical study. BBO-11818. Potent noncovalent pan-KRAS inhibitor targeting ON and OFF states of KRAS G12D, G12V, and G12C. Potently inhibited MAPK signaling and cellular viability in KRAS-driven cell lines. Produced tumor regressions in KRAS-mutant xenograft models. Enhanced efficacy observed in combination with anti-PD-1, anti-EGFR antibodies, and RAS:PI3Kα breaker.	41790032
GIMR	2020-04-16	FL	4	KRAS	G12R	Histiocytosis	Cobimetinib	Case report	29236635
GIMR	2025-06-12	FL	4	KRAS	G12S, G12A, G12C, G12V, G13C, G13D, G13V, Q61E, Q61H, Q61P, A146P, A146T, A146V	Solid tumours	ACBI3	Preclinical study. A single small-molecule degrader, ACBI3, was designed to target 13 of the 17 most prevalent oncogenic KRAS mutants, achieving potent and selective degradation, and inducing tumor regression in KRAS mutant xenograft mouse models.	39298590
GIMR	2021-09-15	FL	4	KRAS	G60_A66dup, E62_A66dup, Switch 2 duplication, Exon 3 insertion	Solid tumours	Mirdametinib	Preclinical study showing KRAS Switch II duplication is oncogenic and sensitive to MEK inhibition.	26854029
GIMR	2026-03-05	FL	4	KRAS	H95L	Solid tumours	Sotorasib; RM-018; RMC-7977	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2025-02-22	FL	4	KRAS	KRAS:Oncogenic mutations + CDH1:Protein expression + VIM:NOT Protein expresssion	Non-small cell lung cancer	Avutometinib + Defactinib	Preclinical study. Epithelial phenotype cells with KRAS-mutated non-small cell lung cancer show an enhanced apoptotic response to avutometinib and defactinib combination therapy through Bim upregulation, but not mesenchymal phenotypes. This study also suggests that EMT status could be a potential predictive biomarker.	38822146
GIMR	2026-03-05	FL	4	KRAS	M72I	Solid tumours	Sotorasib; Divarasib; RM-018; RMC-7977	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2022-06-06	FL	4	KRAS	NOT KRAS:oncogenic mutation	Pancreatic adenocarcinoma	Nimotuzumab + Gemcitabine	NCT00561990. Phase 2. Exploratory analysis of PCS07 trial. In previously untreated, advanced pancreatic cancer, addition of nimotuzumab signficantly prolonged OS at 12 months compared to placebo (54% v 16%) in the KRAS wild type cohort.	28961832
GIMR	2024-10-04	FL	4	KRAS	Oncogenic mutation	Pancreatic adenocarcinoma	Trametinib + Hydroxychloroquine; Trametinib + Palbociclib	Retrospective multicentric cohort study, AIO AIO-TF/PAK-0123, N=34, trametinib + hydroxychloroquine (THCQ) or trametinib + palbociclib (TP) did not show clinical benefit in advanced metastatic pancreatic cancer with KRAS mutations or MAPK/CDKN2A/B alterations.	39352477
GIMR	2020-05-31	FL	4	KRAS	Oncogenic mutations	Colorectal adenocarcinoma	Lifirafenib	No response in 20 patients	32182156
GIMR	2020-07-03	FL	4	KRAS	Oncogenic mutations	Colorectal adenocarcinoma	Onvansertib + FOLFIRI + Bevacizumab; Onvansertib	Phase 1b/2 trial	10.1200/JCO.2020.38.4_suppl.TPS265, NCT03829410
GIMR	2022-01-17	FL	4	KRAS	Oncogenic mutations	Colorectal adenocarcinoma	Selumetinib + Irinotecan	Phase 2. 3 of 32 patient had partial response. The study was terminated before full accrual.	25322874
GIMR	2022-06-04	FL	4	KRAS	Oncogenic mutations	Non-small cell lung cancer	RMC-5552 + RMC-6272	Phase 1. NCT04774952.	10.1200/JCO.2022.40.16_suppl.3098
GIMR	2020-06-15	FL	4	KRAS	Oncogenic mutations	Non-small cell lung cancer	SHP2 inhibitor		29808006
GIMR	2020-06-18	FL	4	KRAS	Oncogenic mutations	Non-small cell lung cancer	Trametinib	Phase 2, ORR 12% but worse PFS than docetaxel	10.1200/jco.2013.31.15_suppl.8029
GIMR	2020-07-02	FL	4	KRAS	Oncogenic mutations	Non-small cell lung cancer	Trametinib + Ponatinib	Intrinsic MEK resistance by FGFR1 activation	27338794, NCT03704688
GIMR	2020-12-30	FL	4	KRAS	Oncogenic mutations	Ovarian cancer	Binimetinib	MILO/ENGOT-ov11. Low-grade serous ovarian cancers. Single-agent binimetinib did not improve PFS. Post-hoc KRAS mutant population ORR 44% (vs. wildtype 19%).	32822286
GIMR	2023-05-13	FL	4	KRAS	Oncogenic mutations	Solid tumour	BI-1701963	NCT04111458	10.1016/j.annonc.2021.08.1046
GIMR	2024-05-27	FL	4	KRAS	Oncogenic mutations	Solid tumour	NST-628	Preclinical study. NST-628, a pan-RAF-MEK molecular glue, demonstrated broad activity in cell line and PDX models with MAPK pathway alterations.	38588399
GIMR	2020-04-16	FL	4	KRAS	Oncogenic mutations	Solid tumours	Binimetinib	Phase 1, ORR 3%	28152546
GIMR	2020-06-26	FL	4	KRAS	Oncogenic mutations	Solid tumours	GGTI-2418		31372813
GIMR	2020-10-30	FL	4	KRAS	Oncogenic mutations	Solid tumours	MEK inhibitor + SHP2 inhibitor		29808009, 30045908, 31068384, 31439712
GIMR	2022-01-15	FL	4	KRAS	Oncogenic mutations	Solid tumours	Ravoxertinib	Phase 1. NCT01875705. N=47. Objective response seen in two BRAF-mutant colorectal cancers. Partial metabolic responses by FDG-PET were seen in 11 of 20 patients.	31848189
GIMR	2022-01-15	FL	4	KRAS	Oncogenic mutations	Solid tumours	SCH772984		23614898
POTTR	2020-04-16	FL	4	KRAS	Oncogenic mutations	Solid tumours	Ulixertinib; LY3214996; LTT462; Ravoxertinib	ERK inhibitors	29431672, 29247021, 10.1200/JCO.2019.37.15_suppl.3001
GIMR	2025-06-11	FL	4	KRAS	Oncogenic mutations, G12A, G12C, G12D, G12F, G12V, G12S, G13C, G13D, V14I, L19F, Q22K, D33E, Q61H, K117N, A146V, A146T	Solid tumours	BI-2493; BI-2865	Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models.	37258666
GIMR	2021-09-28	FL	4	KRAS	Q61H	Non-small cell lung cancer	RAF709 + Trametinib	Preclinical study. KRAS Q61H has high affinity to RAS through formation of a cooperative ternary complex with increased MAPK dependency and sensitivity to MEKi and RAFi inhibition.	32605999
GIMR	2026-03-05	FL	4	KRAS	Q99L	Solid tumours	Sotorasib; Adagrasib; Divarasib; RM-018; RMC-7977	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2026-03-05	FL	4	KRAS	R68S	Solid tumours	RM-018; RMC-7977	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2026-03-05	FL	4	KRAS	Y96D	Solid tumours	RM-018; RMC-7977	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2020-07-03	FL	4	KRAS+ERBB3	KRAS:Oncogenic mutations and ERBB3:Overexpression	Non-small cell lung cancer; Colorectal adenocarcinoma	Afatinib + Selumetinib	By ERBB3 overexpression	24685132
GIMR	2025-06-10	FL	4	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	H231	Preclinical study. ADCs targeting EGFR ligand epiregulin (EREG) demonstrate antitumor activity in colorectal cancer across RAS mutation status, offering a potential alternative to conventional EGFR-targeted therapy.	39693606
GIMR	2026-03-04	FL	4	KRAS+NRAS+Consensus molecular subtype	Consensus molecular subtype:CMS4 and NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	Cetuximab; Panitumumab	IPD Meta-Analysis. FIRE1, FIRE3, XELAVIRI, PanaMa, TRIBE2. N=790. RAS WT mCRC. CMS4 anti-EGFR vs anti-VEGF PFS HR 0.67 (P = .03), OS HR 0.49 (P < .001). CMS2/CMS4 vs CMS1 ORR OR 1.668/1.369, PFS HR 0.64/0.67, OS HR 0.59/0.67. Interaction test PFS/OS P < .001. CMS4 potential biomarker for anti-EGFR efficacy.	41252656
GIMR	2021-04-07	FL	4	KRAS+STK11	KRAS:G12C and STK11:Oncogenic mutations	Non-small cell lung cancer	Adagrasib	KRYSTAL-1. Higher ORR was seen in 64% (9/14) with STK11 mutations	10.1016/S1556-0864(21)01941-9
GIMR	2020-05-31	FL	4	LRP1B	Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Retrospective study. Significantly better outcomes with immune checkpoint inhibitors were seen in patients harboring pathogenic alteration of LRP1B gene, where longer PFS (HR 0.42) and OS (HR 0.62) were observed.	33653800, 10.1200/JCO.2020.38.15_suppl.3007
GIMR	2025-07-02	FL	4	LTK	CLIP1-LTK fusion	Non-small cell lung cancer	Lorlatinib; Crizotinib; Alectinib; Ceritinib; Brigatinib; Entrectinib; Repotrectinib; Gilteritinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	I565N, F568C, G663A	Non-small cell lung cancer	Alectinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	I565N, F568C, L590M, G596R, D597N, G663A	Non-small cell lung cancer	Ceritinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	I565N, F568C, L590M, L592F, D597N, L650F, G663A	Non-small cell lung cancer	Gilteritinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	I565N, F568C, L590M, L592F, G596R, D597N, G663A	Non-small cell lung cancer	Lorlatinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	I565N, L590M, D597N, G663A	Non-small cell lung cancer	Brigatinib; Entrectinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	I565N, L590M, L592F, G596R, D597N, G663A	Non-small cell lung cancer	Repotrectinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	4	LTK	L592F	Non-small cell lung cancer	Crizotinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2020-11-26	FL	4	LZTR1	Loss-of-function mutations	Chronic myelogenous leukaemia	Trametinib	LZTR1 lof mutation decreases RAS ubiquitination and is associated with resistance, reverted by MEK inhibitor in a CML model	30442766
GIMR	2020-02-08	FL	4	MAP2K1	K57_G61del	Histiocytosis	Trametinib	Case report. Langerhans cell histiocytosis responder to Trametinib.	32991018
GIMR	2021-04-06	FL	4	MAP2K1	K57N, Q56P	Non-small cell lung cancer	Selumetinib	Cell line study showing NSCLC cells sensitive to AZD6244	18632602
GIMR	2020-04-16	FL	4	MAP2K1	Oncogenic mutations	Melanoma; Non-small cell lung cancer	Cobimetinib; Trametinib	Trametinib showed activities in treating cell lines or patients with MEK1 mutations across various malignancies, suggesting MEK1 mutations as potential indications for trametinib therapy, although resistance was observed with varying responses to different MEK1 mutations.	31715422
GIMR	2020-05-15	FL	4	MAP2K1	Oncogenic mutations	Solid tumours	Ulixertinib	Preclinical study. ERK inhibitor ulixertinib showed therapeutic potential against BRAF mutant, BRAF-MEK inhibitor resistant, or RAS mutant tumors with clinical activity against various tumor types in a first-in-human dose-escalation study.	29431672
GIMR	2020-05-20	FL	4	MAP2K1	Q56_V60del, Negative regulatory domain deletion	Low-grade serous ovarian cancer	Selumetinib	Case report and genomic analysis. A patient with low-grade serous ovarian cancer experienced a complete and durable response to selumetinib, with tumour harbouring a 15-nucleotide deletion in MAP2K1 gene encoding MEK1, and 82% of 28 analysed tumours had ERK pathway-activating mutations, including BRAF fusions.	26324360
GIMR	2021-10-22	FL/JG	4	MAP2K2	C125S	Melanoma	VX11E	Progression biopsy and cell line studies. Mutation conferring on-target acquired resistance to both RAF and MEK inhibition, including C125S, remains sensitive to ERK inhibition.	24265153
GIMR	2020-05-31	FL	4	MAP2K2	Q60P	Melanoma	Dabrafenib + Trametinib + Omipalisib	Preclinical study. Concurrent MEK2-Q60P mutation and BRAF amplification/V600E were identified in melanoma cells resistant to BRAF and MEK inhibitors, conferring sustained MAPK activation and on-target resistance, which was addressed by a triple combination of dabrafenib, trametinib, and GSK2126458.	24055054
JGKB	2020-04-16	FL	4	MAP2K4	Oncogenic mutations	Solid tumours	Selumetinib		29795445
JGKB	2020-04-16	FL	4	MAP3K1	Oncogenic mutations	Solid tumours	Selumetinib		29795445
GIMR	2023-06-22	FL	4	MAP3K1+PIK3CA	MAP3K1:Oncogenic mutations AND PIK3CA:Oncogenic mutations 	Breast cancer	Buparlisib + Letrozole; Alpelisib + Letrozole	Retrospective study from MSK-IMPACT. The clinical benefit associated with combined PI3K and ER inhibition in ER+ breast cancer harbouring MAP3K1 alteration, which may be associated with luminal A status.	31552290
GIMR	2023-03-13	FL	4	MAPK1	D321N	Head and neck squamous cell carcinoma	Erlotinib	Cell line study showing HNSCC cell line harbouring MAPK1 D321N mutation is sensitive to erlotinib in vivo.	32351709
GIMR	2023-03-13	FL	4	MAPK1	E322K	Head and neck squamous cell carcinoma	Erlotinib	Case report. The HNSCC cells with MAPK1 E322K mutation causes constitutive activation of ERK2 and is associated erlotinib sensitivity in cell line models.	26181029
GIMR	2020-11-03	FL	4	MCL1	Amplification	Endometrial cancer	Fadraciclib		10.1016/S0959-8049(20)31086-8
SuboKB	2020-04-16	FL	4	MCL1	Amplification	Solid tumours	Dinaciclib		25289887
GIMR	2020-07-03	FL	4	MDM2	Amplification, Overexpression	Solid tumours	Milademetan Tosylate	2 PR in synovial sarcoma. 1 DDLPS	10.1200/JCO.2018.36.15_suppl.11514, 10.1016/S0959-8049(20)31080-7
GIMR	2023-08-01	FL	4	MDM2+TP53	MDM2:Amplification AND NOT TP53:Oncogenic mutations	Cholangiocarcinoma; Pancreatic adenocarcinoma	Brigimadlin	Response seen in one case each of cholangiocarcinoma and pancreatic carcinoma in Brightline-1	37269344
GIMR	2024-06-02	FL	4	MDM2+TP53+IDH1	MDM2:Amplification AND NOT TP53:Oncogenic mutations AND NOT IDH1:Oncogenic mutations	Glioblastoma	Navtemadlin	Preclinical study: Navtemadlin showed activities in TP53 wildtype GBM flank PDX models, but CNS penetration was limited by P-gp. Intratumoral levels required for efficacy varied is dependent on MDM2 amplification status.	10.1200/JCO.2024.42.16_suppl.2012
GIMR	2020-11-03	FL	4	MET	Alterations	Solid tumours	Elzovantinib		10.1016/S0959-8049(20)31074-1
GIMR	2023-07-04	FL	4	MET	Amplification	Colorectal adenocarcinoma	Crizotinib; Crizotinib + Cetuximab	Xenograft models. MET inhibitors could be effective in overcoming the resistance caused by MET amplification associated with anti-EGFR therapy.	23729478
GIMR	2022-01-18	FL	4	MET	Amplification	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Crizotinib	Case series. Two partial responders to crizotinib.	22042947
GIMR	2026-03-04	FL	4	MET	Amplification	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1/2. Patritumab Deruxtecan (HER3-DXd). N=47. Advanced NSCLC without common EGFR mutation progressed on platinum-based chemotherapy and immunotherapy. Primary endpoint cORR was 27.7% (95% CI, 15.6% to 42.6%). Median DOR 8.1 months. Median PFS 5.5 months. Median OS 15.2 months. Similar efficacy observed in patients with and without identified driver genomic alterations. Note 1 case of MET amplification had best response of PD.	40554742
GIMR	2020-04-16	FL	4	MET	Amplification	Solid tumours	Telisotuzumab Vedotin		30285518, 34426443, 10.1200/JCO.2019.37.15_suppl.3011
GIMR	2020-05-15	FL	4	MET	Amplification	Triple-negative breast cancer	Crizotinib		32234363
GIMR	2023-06-23	FL	4	MET	Amplification, Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	GB263T	Cell line study.	10.1158/1538-7445.AM2022-LB538
GIMR	2021-07-13	FL	4	MET	Amplification, Overexpression, Exon 14 skipping mutation	Solid tumours	ABN401		32549194
GIMR	2022-07-20	FL	4	MET	CAV1-MET fusion	Non-small cell lung cancer; Small-cell lung cancer	Crizotinib	Case report. Objective response was seen in SCLC transformation with Inframe fusion of exons 1-2 of CAV1 to exons 2-21 of MET on the background of EGFR L858R.	31122565
GIMR	2025-02-05	FL	4	MET	CD47-MET fusion	Non-small cell lung cancer	Capmatinib	Case report: Complete response in patient with metastatic NSCLC harboring CD47-MET fusion treated with capmatinib, achieving 18-month ongoing complete metabolic response after 3 prior lines of therapy.	38832711
GIMR	2022-07-04	FL	4	MET	D1028H (D1010H)	Non-small cell lung cancer	Crizotinib	Case report. c.3082G>C could result in skipping of exon 14. Radiographic response to crizotinib was observed.	25898962
GIMR	2021-01-03	FL	4	MET	D1028H (D1010H)	Non-small cell lung cancer	Crizotinib	Case report. MET Y1230C mutation (0.3% pre-treatment frequency) emerged as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping, co-occurring with METex14 alteration D1010H, and was detected in ctDNA at progression after 13 months of treatment.	27666659
GIMR	2022-07-04	FL	4	MET	D1028N (D1010N)	Non-small cell lung cancer	Crizotinib	Case report. 	26892698
GIMR	2020-05-15	FL	4	MET	D1228	Triple-negative breast cancer	Cabozantinib		32234363
GIMR	2021-01-03	FL	4	MET	Exon 14 deletion, Exon 14 splicing mutation,  Exon 14 skipping mutation	Non-small cell lung cancer	Crizotinib	Case reports	26845194, 27022036
GIMR	2021-01-03	FL	4	MET	Exon 14 deletion, Exon 14 splicing mutation,  Exon 14 skipping mutation	Non-small cell lung cancer	Crizotinib; Cabozantinib	Case series.	26896094
GIMR	2020-05-15	FL	4	MET	Exon 14 deletion, Exon 14 splicing mutation,  Exon 14 skipping mutation, Y1003 (Y1021), D1010 (D1028), Amplification, D1228, G1163	Non-small cell lung cancer	Cabozantinib	Cabozantinib has activities; Note MET IHC not a biomarker	30762593, 27825638, 27693535
GIMR	2021-10-19	FL	4	MET	Exon 14 Deletion, Exon 14 splicing mutation, Exon 14 skipping mutation	Non-small cell lung cancer	Amivantamab	CHRYSALIS. NCT02609776. N=16. MET-2 cohort. 4 Confirmed partial responses.	10.1016/j.jtho.2021.08.084
GIMR	2021-10-07	FL	4	MET	Exon 14 skipping mutation, c.2888-5_2944del	Histiocytic sarcoma	Crizotinib	Case report of response Crizotinib in met Exon 14 skipping histocytic sarcoma	25971938
GIMR	2020-05-15	FL	4	MET	Fusions	Non-small cell lung cancer; Glioblastoma	Crizotinib	Case reports	29527595, 30339198, 27748748
GIMR	2025-05-27	FL	4	MET	H1106D, H1094Y, N1100S, R1170Q, M1250T	Non-small cell lung cancer	Crizotinib 	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2023-03-29	FL	4	MET	Overexpression	Head and neck squamous cell carcinoma	Ficlatuzumab + Cetuximab	NCT03422536. In treatment refractory HNSCC, patients in the Ficlatuzumab + Cetuximab combination arm resulted in significant hazard reduction for progression of 0.3 in cMET positive subgroup, defined as H-score of >= 150	36977289
GIMR	2022-06-04	FL	4	MET	Overexpression	Non-small cell lung cancer	ABN401	Phase 1. NCT04052971. Two responders were seen in tumour with MET overexpressed NSCLC.	10.1200/JCO.2022.40.16_suppl.3105
GIMR	2023-09-09	FL	4	MET	Overexpression	Non-small cell lung cancer; Gastroesophageal junction adenocarcinoma; Gastric Cancer; Endometrial carcinoma; Acral melanoma	ABBV-400	Phase 2. NCT05029882. Clinical activity was observed with ABBV-400 with an ORR of 24% (11/45). All responses were confirmed partial responses. DCR was 81%. Overexpression was determined IHC. 	10.1200/JCO.2023.41.16_suppl.3015
GIMR	2023-12-08	FL	4	MET	Overexpression	Solid tumour; Non-small cell lung cancer	MTYX-5000	Preclinical study. MYTX-011 showed activities in higher internalization in cMet+ tumor cells, cytotoxicity across a cMet+ cancer cell lines in vitro, and in NSCLC xenograft models.	10.1158/1538-7445.AM2023-5000
GIMR	2021-09-30	FL	4	MET	Overexpression	Solid tumours	Telisotuzumab Vedotin		33675179, 10.1200/JCO.2019.37.15_suppl.9023
GIMR	2024-10-04	FL	4	MET	Protein expression	Non-small cell lung cancer	MYTX-011	Phase 1. MYTX-011 showed improved payload delivery to c-MET-expressing tumor cells, with increased cytotoxicity and efficacy in NSCLC xenograft models.	38684230
GIMR	2025-04-23	FL	4	MET	Protein expression; Overexpression	Colorectal adenocarcinoma	ABBV-400	Phase 1. NCT05029882. N=122. ABBV-400 demonstrated preliminary efficacy with ORR of 15% at 2.4 mg/kg and 20% at 3.0 mg/kg Q3W, accompanied by a tolerable safety profile. ORR was correlated with c-Met expression.	10.1200/JCO.2024.42.16_suppl.3515
GIMR	2022-12-20	FL	4	MET	PTPRZ-MET fusion, TFG-MET fusion	Glioblastoma	Crizotinib; Foretinib		27748748
GIMR	2025-05-27	FL	4	MET	V1092I, H1094Y, N1100S, H1106D, R1170Q, L1195V, F1200I, M1250T	Non-small cell lung cancer	Capmatinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2025-05-27	FL	4	MET	V1092I, H1094Y, N1100S, H1106D, R1170Q, M1250T	Non-small cell lung cancer	Elzovantinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2025-05-27	FL	4	MET	V1092I, H1094Y, N1100S, H1106D, R1170Q, M1250T	Non-small cell lung cancer	Tepotinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2025-05-27	FL	4	MET	V1092I, H1094Y, N1100S, H1106D, R1170Q, Y1230H	Non-small cell lung cancer	Cabozantinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2021-01-03	FL	4	MET	Y1003S (Y1021S)	Non-small cell lung cancer	Crizotinib	Case report showing significant response and DOR	30885356
GIMR	2021-01-03	FL	4	MET	Y1021H (Y1003H)	Non-small cell lung cancer	Crizotinib	Case report, sensitive to Crizotinib	31809977
GIMR	2021-08-13	FL	4	MET	Y1248H (Y1230H), D1246N (D1228N), K1262R (K1244R)	Solid tumours	Cabozantinib		21926191
GIMR	2022-01-12	FL	4	MET+KRAS	MET:Amplification and KRAS:G12V	Solid tumours	Crizotinib	Case report. Durable response over 19 months in a MET-amplified (16 copies, detected by next sequencing) carcinoma of unknown primary, with co-mutation of KRAS G12V. 	25232318
POTTR	2020-04-16	FL	4	MGMT	Loss of protein expression	Glioblastoma	Temozolomide		15758010
JGKB	2020-04-16	FL	4	MGMT	Loss-of-function mutations	Solid tumours	Alkylating agent	Predicted LOF. Check IHC	15888787
GIMR	2022-06-06	FL	4	MGMT	Low protein expression, Methylation	Pancreatic neuroendocrine tumour	Capecitabine + Temozolomide	NCT01824875. E2211 trial. Higher odds of response to temozolomide was seen in MGMT Low protein expression (by IHC) or promoter methylation, with odds ratio of 6.4.	10.1200/JCO.2022.40.16_suppl.4004
GIMR	2024-06-02	FL	4	MGMT	Unmethylated	Glioblastoma	Niraparib + Radiotherapy		10.1200/JCO.2024.42.16_suppl.2002
GIMR	2021-08-15	FL	4	Microsatellite Instability	High	Colorectal adenocarcinoma	Atezolizumab	Phase 3 IMBlaze 370. MSI-H subgroup. 3/6 response (50%) in MSI high group.	31003911
GIMR	2025-10-18	FL	4	Microsatellite Instability	High	Colorectal adenocarcinoma	HRO761	Phase I/Ib. HRO761. NCT05838768. N=47 (19 CRC). ORR 8.6% (10.5% in CRC), DCR 68.6% (84.2% in CRC), median PFS 5.6 months; 9-mo PFS rate 68.6% (95% CI 30.5–88.7) at 200 mg daily. ctDNA clearance observed in 6/14 pts with detectable baseline ctDNA, median treatment duration 9.3 months in responders.	ESMO25.925MO
GIMR	2025-01-20	FL	4	Microsatellite Instability	High	Endometrial cancer	Avelumab + Carboplatin + Paclitaxel	Phase 2. MITO END-3 trial. NCT03503786. N=125. Compared with chemotherapy alone, avelumab efficacy varied by molecular profiling with favorable PFS in MSI-H and worst in MSS/TP53 mut in first-line endometrial cancer therapy. Significant interactions in PFS were observed in patients with ARID1A and PTEN mutations.	38704093
GIMR	2025-06-10	FL	4	Microsatellite Instability	High	Solid tumours	ATX968	Preclinical study. Selective inhibition of DHX9 by a small-molecule inhibitor impairs proliferation of microsatellite instable-high and mismatch repair deficient cancers in vitro and xenograft models.	39589774
GIMR	2025-02-04	FL	4	Microsatellite Instability	High	Solid tumours	GSK_WRN4	Preclinical study. Novel WRN helicase inhibitors selectively targeted microsatellite unstable cancer cells by mimicking WRN loss, inducing DNA double-strand breaks at expanded TA-repeats and DNA damage, with activities confirmed in immunotherapy-resistant organoids and patient-derived xenograft models.	38587317
POTTR	2020-04-16	FL	4	Microsatellite Instability	High	Solid tumours	immune checkpoint blockade,CTLA-4 targeting; immune checkpoint blockade,PD-L1 targeting; immune checkpoint blockade,PD-1 targeting		30787022
GIMR	2025-02-10	FL	4	Microsatellite Instability	High	Solid tumours	MDNA11	Phase 1/2 ABILITY-1 trial. NCT05086692. N=30. MDNA11 showed single-agent activity in advanced solid tumors, with ORR of 7.7% and CBR of 19.2% in 26 evaluable patients, including one confirmed PR in a PDAC (MSI-H) patient.	10.1158/1538-7445.AM2024-CT259
GIMR	2025-05-26	FL	4	Microsatellite Instability	High	Solid tumours	MOMA-341	Preclinical study. MOMA-341, a novel WRN inhibitor, showed antitumor activity in MSI-H models in preclinical studies. Direct measurement of TA repeat expansions by long-read sequencing outperformed MSI-H status as a predictor of sensitivity, enabling near-perfect prediction of MOMA-341 anti-tumor activity.	10.1158/1538-7445.AM2025-4205
GIMR	2021-09-23	FL	4	Mismatch repair	Deficient	Pancreatic adenocarcinoma	Pembrolizumab; Nivolumab + Ipilimumab	Retrospective series. N=6 (evaluable). Median PFS 8.2 months.	10.1200/JCO.2021.39.3_suppl.415
GIMR	2025-06-10	FL	4	Mismatch repair	Deficient	Solid tumours	ATX968	Preclinical study. Selective inhibition of DHX9 by a small-molecule inhibitor impairs proliferation of microsatellite instable-high and mismatch repair deficient cancers in vitro and xenograft models.	39589774
POTTR	2020-04-16	FL	4	Mismatch repair	Deficient	Solid tumours	immune checkpoint blockade,CTLA-4 targeting; immune checkpoint blockade,PD-L1 targeting; immune checkpoint blockade,PD-1 targeting		26028255, 31682550, 10.1158/1078-0432.CCR-18-4070
SuboKB	2020-04-16	FL	4	MLH1	Loss-of-function mutations	Colorectal adenocarcinoma	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Check MSI IHC	26895986
GIMR	2021-06-15	FL	4	Molecular subtype	BLIA molecular subtype	Triple-negative breast cancer	Atezolizumab + Nab-paclitaxel	Retrospective analysis from IMpassion130. BLIA molecular subtypes showed both improved PFS and OS in PD-L1 IC-positive subgroup. Molecular subtypes assessed using Burstein classification.	10.1200/JCO.2021.39.15_suppl.1006
GIMR	2022-02-02	FL	4	MRE11A	L169Rfs*14, oncogenic mutations (germline)	Mesothelioma	Olaparib	Phase 2. NCT03531840. Olaparib has no activity in previously treated mesothelioma harbouring BAP1 mutations, except for a sole responder with germline MRE11A mutation. MRE11A is not in the inclusion criteria.	34661178
GIMR	2021-06-09	FL	4	MRE11A	Loss-of-function mutations	Breast cancer	Olaparib; PDD00017273	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
SuboKB	2020-04-16	FL	4	MSH2	Loss-of-function mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Check MSI IHC	26895986
GIMR	2021-08-04	FL	4	MSH2	R359S (germline)	Glioblastoma	Nivolumab	Case report of prolonged response to Nivolumab	33140187
SuboKB	2020-04-16	FL	4	MSH6	Loss-of-function mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Check MSI IHC	26895986
GIMR	2020-06-28	FL	4	MSLN	Protein expression, Overexpression	Mesothelioma	Amatuximab	Phase 2 trial. PFS not different from historical control.	25231400
GIMR	2020-06-28	FL	4	MSLN	Protein expression, Overexpression	Solid tumours; Mesothelioma; Ovarian cancer	Anetumab Ravtansine	Phase 1 study. Anetumab ravtansine showed clinical activity in patients with high mesothelin expression, with 1 complete response and 11 partial responses among 148 patients with various solid tumors, including mesothelioma and ovarian cancer.	32213105
GIMR	2023-12-14	FL	4	MTAP	Deletion	Solid tumour; Mesothelioma; Non-small cell lung cancer; Gallbladder cancer; Malignant peripheral nerve sheath tumor	MRTX1719	Phase 1 trial and preclinical study. NCT05245500. In vitro cell line models and xenografts studies. MRTX1719 selectively inhibited PRMT5 in MTAP-deleted tumor cells with minimal effects on normal hematopoietic cells. Early clinical activity were observed in patients seleced cancer types.	37552839
POTTR	2020-04-16	FL	4	MTAP	Deletion	Solid tumours	AG-270	Preclinical study. MAT2A inhibitors showed selective growth inhibition in MTAP-deleted cancer cells and tumors, with efficacy correlated to MTAP deletion across >300 cell lines, and induced defects in RNA splicing, leading to antiproliferative effects, with potential for combination strategies with cell cycle or DNA repair inhibitors.	10.1158/1538-7445.AM2019-2714
GIMR	2025-05-27	FL/MK	4	MTAP	Deletion	Solid tumours	AG-270	Phase 1 trial. NCT03435250. N=40. AG-270/S095033, a MAT2A inhibitor, achieved 2 partial responses and 5 patients with stable disease ≥16 weeks in patients with advanced MTAP-deleted malignancies. First curated: 2020-11-23	39762248
GIMR	2025-04-28	FL	4	MTAP	Deletion	Solid tumours	AMG-193	Preclinical study. The PRMT5 inhibitor showed confirmed partial responses in patients with MTAP-deleted solid tumors and demonstrated synergistic antitumor activity when combined with chemotherapies or sotorasib in preclinical models." 	39282709
POTTR	2020-04-16	FL	4	MTAP	Deletion	Solid tumours	GSK3368715	Preclinical study. GSK3368715, a type I PRMT inhibitor, showed anti-tumor effects and synergy with PRMT5 inhibition, particularly in MTAP-deficient cancer models, suggesting MTAP status as a potential biomarker for patient selection.	31257072
GIMR	2020-04-16	FL	4	MTOR	E2014K, E2419K	Urothelial carcinoma	Everolimus	Phase 2 study. Everolimus showed biological activity in a subset of patients with advanced urothelial carcinoma, with 2 partial responses and 12 minor regressions, suggesting a potential role for mTOR pathway inhibition, although no clear association was observed between mTOR pathway marker expression and response.	23551593
GIMR	2020-04-16	FL	4	MTOR	L1460P, L2209V, L2427Q	Renal cell carcinoma	Temsirolimus	Retrospective observational study. Mutations in MTOR, TSC1, or TSC2 were associated with response to rapalogs in metastatic renal cell carcinoma patients, with higher frequency of mutations in responders (28%) compared to nonresponders (11%).	26831717
GIMR	2020-04-16	FL	4	MTOR	Oncogenic mutations	Breast cancer	Temsirolimus	Phase 2 study. Temsirolimus showed antitumor activity with an ORR of 9.2% in heavily pretreated patients with locally advanced or metastatic breast cancer, with similar efficacy observed at both 75mg and 250mg doses.	15955899
GIMR	2020-04-27	FL	4	MTOR	Oncogenic mutations	Renal cell carcinoma	Everolimus	Drug is PBS reimbursed, but not biomarker selected	26831717
GIMR	2020-04-16	FL	4	MTOR	Q2223K	Renal cell carcinoma	Everolimus	Retrospective observational study. Mutations in MTOR, TSC1, or TSC2 were associated with response to rapalogs in metastatic renal cell carcinoma patients, with higher frequency of mutations in responders (28%) compared to nonresponders (11%).	26831717
GIMR	2021-06-18	FL	4	MTORC1	Oncogenic mutations	Solid tumours	Sapanisertib + Metformin	Phase 1 trial. NCT03017833. N=30. Sapanisertib + metformin showed anti-tumor activity in patients with mTOR/AKT/PI3K pathway alterations, including 4 patients achieving partial response, 3 of whom had PTEN mutations and 1 had AKT and mTOR mutation.	10.1200/JCO.2021.39.15_suppl.3017
GIMR	2025-06-04	FL	4	MUC1	Protein expression	Solid tumours	DM002	Preclinical study. DM002 is a bispecific antibody-drug conjugate targeting HER3 and the juxtamembrane domain of MUC1, demonstrating endocytic and anti-tumor activity in patient-derived xenograft models of lung, breast, gastric, and pancreatic cancers.	10.1158/1538-7445.AM2023-LB214
GIMR	2023-04-08	FL	4	Mutational signature	SBS3 signature	Osteosarcoma	Olaparib	Case report. Prolonged complete response in radiotherapy-associated osteosarcoma with biallelic FANCM loss, high HRD score, and SBS3 mutational signature.	36848605
GIMR	2021-05-05	FL	4	MYB	Alteration; Overexpression	Solid tumours; Adenoid cystic carcinoma; Colorectal adenocarcinoma	TetMYB	Phase1. MYPHISMO. NCT03287427. First-in-human trial evaluating the safety and efficacy of TetMYB vaccine in combination with anti-PD-1 antibody in patients with advanced solid cancers, including colorectal and adenoid cystic carcinoma.	31650066
GIMR	2025-04-13	FL	4	MYB	Overexpression; MYB-NFIB fusion	Adenoid cystic carcinoma	VX-970	Preclinical study. ATR kinase inhibitor VX-970 induced apoptosis in MYB-positive adenoid cystic carcinoma cells and growth inhibition in ACC patient-derived xenografts, identifying ATR as a potential therapeutic target downstream of MYB activation.	32001675
GIMR	2025-02-17	FL	4	MYC	Amplification	Neuroblastoma	Isotretinoin + Navitoclax	Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models.	38942989
GIMR	2022-02-27	FL	4	MYC	Amplification	Solid tumours	T-025	Cell line study. CLK inhibitor showed stronger anti‐proliferative effects for cell lines of MYC‐amplified solid tumours than non‐amplified counterparts.	29769258
POTTR	2020-04-16	FL	4	MYC	Amplification, Oncogenic mutations	Solid tumours; Liquid cancers	BET inhibitor	Review of bromodomain inhibitors, a new target class for drug development, highlighting the progress of BET inhibitors in clinical trials and discussing the potential of next-wave non-BET bromodomain inhibitors in oncology and non-oncology indications.	31273347
GIMR	2021-03-06	FL	4	MYC	Amplification, Overexpression	Neuroblastoma	CX-5461	Preclinical study. CX-5461 down-regulates MYCN protein and suppresses neuroblastoma tumor growth, particularly in MYCN-amplified tumors. Xenograft models using the KELLY cell line demonstrate orthotopic tumor growth suppression following CX-5461-induced MYCN downregulation.	30879743
GIMR	2025-06-25	FL	4	MYC	Amplification, Overexpression	Small-cell lung cancer	Mivebresib	Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1.	38747975
GIMR	2021-06-12	FL	4	MYCL	Overexpression	Small-cell lung cancer	CX-5461	Preclinical study. MYCL amplification in SCLC promotes tumor-forming capacity and ribosomal biogenesis, and deletion of Mycl suppresses SCLC, suggesting RNA Pol I inhibition as a potential therapeutic target, which showed significant tumor inhibition in an autochthonous Rb/p53-deleted mouse SCLC model.	27298335
GIMR	2022-08-03	FL	4	MYCN	Amplification	Neuroblastoma	CX-5461; Quarfloxin	Cell line and Xenograft studies. In neuroblastoma cell lines, RNA polymerase I inhibitors have been shown to suppress n-myc expression and induced cell cycle arrest and apoptosis.	30542116
GIMR	2025-02-17	FL	4	MYCN	Amplification	Neuroblastoma	Isotretinoin + Navitoclax	Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models.	38942989
POTTR	2020-04-16	FL	4	MYCN	Amplification, Oncogenic mutations	Solid tumours; Liquid cancers	BET inhibitor	Preclinical studies demonstrated bromodomain inhibition as a therapeutic strategy in cancer, particularly for MYCN-amplified neuroblastoma, where BET bromodomain inhibitors downregulated the MYCN transcriptional program and impaired growth, inducing apoptosis, and conferred a significant survival advantage in in vivo models.	23430699, 31273347
GIMR	2021-03-06	FL	4	MYCN	Amplification, Overexpression	Neuroblastoma	CX-5461	Xenograft model established on KELLY cell line CX-5461 leads to MYCN downregulation and suppress orthotopic tumour growth.	30879743
GIMR	2021-03-06	FL	4	MYCN	Amplification, Overexpression	Neuroblastoma	CX-5461; Halofuginone	Both Halofuginone and CX-5461 suppressed neuroblastoma in vitro, most notably in MYCN amplified and TP53 wildtype cell-line.	29464082
GIMR	2025-06-25	FL	4	MYCN	Amplification, Overexpression	Small-cell lung cancer	Mivebresib	Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1.	38747975
GIMR	2020-10-26	FL	4	MYCN	Amplification; Overexpression	Neuroblastoma	LY3295668		NCT04106219; 10.1200/JCO.2020.38.15_suppl.TPS10561
JGKB	2020-04-16	FL	4	MYD88	Gain-of-function mutations	Diffuse large B-cell lymphoma	eFT508	Preclinical study. MNK1/MNK2 inhibitor demonstrated anti-proliferative effects in DLBCL cell lines, reduced pro-inflammatory cytokine production, and showed anti-tumor activity in human lymphoma xenograft models.	10.1182/blood.V126.23.1554.1554
GIMR	2020-11-12	FL	4	NBN	Oncogenic mutations	Prostate cancer	Olaparib	Hypothetical biomarker in TOPARP. Only one patient in the entire cohort.	31806540
GIMR	2020-11-12	FL	4	NBN	Oncogenic mutations	Prostate cancer	Olaparib	TRITON2. No PSA response in 4 patients.	32086346
GIMR	2024-04-27	FL	4	NECTIN4	Amplification	Urothelial carcinoma	Enfortumab Vedotin	Retrospective cohort. N=108. NECTIN4-specific amplifications by FISH assay (NECTIN4/CEN1 ratio) > 2.0. NECTIN4 amplification was associated with enhanced membranous protein expression, as well as objective response to enfortumab vedotin with longer OS and response rate (82% vs 32% non-amplified).	38657187
GIMR	2025-06-09	FL	4	NECTIN4	Protein expression	Solid tumours	ADRX-0706	Phase 1 trial. NCT06036121. N=53. ADRX-0706, a Nectin-4 targeting antibody-drug conjugate (ADC), showed anti-tumor activity in 30 response-evaluable subjects treated at doses ≥8 mg/kg, with a confirmed complete response in a cervical cancer patient. The study reported an ORR of 17%, including 5 objective responses, and a DCR of 47%, with 9 patients experiencing stable disease. Nectin-4 expression is retrospective analysis criteria and not prospectively assessed.	10.1200/JCO.2025.43.16_suppl.3018
GIMR	2022-06-11	FL	4	NECTIN4	Protein expression	Solid tumours	Enfortumab Vedotin	Phase 1 EV-101 study. Enfortumab vedotin showed antitumor activity in Nectin-4-positive metastatic urothelial carcinoma patients, with an ORR of 43% and median OS of 12.3 months, indicating sensitivity to the drug in heavily pretreated patients.	32031899
GIMR	2021-03-28	FL	4	NECTIN4	Protein expression	Urothelial carcinoma	Enfortumab vedotin	NECTIN4 mediates sensitivity to enfortumab vedotin, and its downregulation leads to treatment resistance. NECTIN4 is enriched in luminal subtypes of bladder cancer. 	10.1200/JCO.2021.39.6_suppl.463
GIMR	2021-04-19	FL	4	NF1	Loss-of-function mutations, deletion	Malignant peripheral nerve sheath tumor	SHP099		10.1158/1538-7445.AM2020-1889
GIMR	2021-04-19	FL	4	NF1	Loss-of-function mutations, deletion	Malignant peripheral nerve sheath tumor	Trametinib + RMC-4550; SHP099	Combined MEK/SHP2 inhibition was shown to be effective in models of NF1-deficient MPNST cell line models.	33032988
GIMR	2020-04-16	FL	4	NF1	Oncogenic mutations	Glioblastoma; Type 1 neurofibromatosis	Trametinib	Case report. Treatment-refractory neurofibromatosis-associated glioblastoma experienced clinical and radiological benefit from the MEK inhibitor, trametinib.	26936308
GIMR	2025-03-07	FL	4	NF1	Oncogenic mutations	Melanoma	Avutometinib + BI-3406	Preclinical study. Concurrent SOS1 and MEK inhibition suppressed signaling and growth of NF1-null melanoma, abrogated ERK activation, induced cell death, and suppressed tumor growth.	39488215
GIMR	2020-11-03	FL	4	NF1	Oncogenic mutations	Solid tumours	Vociprotafib + Cobimetinib	Phase 1 trial.	10.1016/S0959-8049(20)31089-3
GIMR	2020-05-14	FL	4	NF1	Oncogenic mutations (germline)	Glioblastoma	Trametinib 	Case report. A 24-year-old male with neurofibromatosis type I-associated glioblastoma showed clinical and radiological benefit from the MEK inhibitor, trametinib.	26936308
GIMR	2021-06-12	FL	4	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis	FCN-159	Phase 1. NCT04954001. Adult patient population. Using ReiINS criteria, 16/16 patients showed decreased tumour volume with 6/16 (38%) had tumor size reduction by at least 20%.	10.1200/JCO.2022.40.16_suppl.3011
GIMR	2025-03-07	FL	4	NF1	Oncogenic mutations (germline)	Type 1 neurofibromatosis 	Abemaciclib + LY3214996	Preclinical study. Combined CDK4/6 and ERK1/2 inhibition enhanced antitumor activity in NF1-associated plexiform neurofibroma, with abemaciclib and LY3214996 synergizing to suppress MAPK activation and exhibiting enhanced antitumor activity in mouse models.	37406085
GIMR	2022-01-12	FL	4	NF1	Oncogenic mutations, Loss-of-function mutations	Melanoma	Trametinib	Case report. A patient with NF1-mutated melanoma refractory to immunotherapy and chemotherapy responded to trametinib, a MEK inhibitor, with a DOR of 5 months, and showed increased CD8+ infiltration and PD-L1 expression during treatment.	10.1200/PO.18.00028
GIMR	2022-02-04	FL	4	NF1	Oncogenic mutations, Loss-of-function mutations, N184fs, Q1336*	Solid tumours	RMC-4550	Preclinical study. SHP2 phosphatase inhibitor RMC-4550 was effective in human cancer models with RAS-GTP-dependent oncogenic BRAF (class 3 BRAF mutants), NF1 loss, or nucleotide-cycling oncogenic RAS (KRAS(G12C)), by disrupting SOS1-mediated RAS-GTP loading and decreasing oncogenic RAS/RAF/MEK/ERK signalling.	30104724
GIMR	2022-07-12	FL	4	NF1+MET	NF1:Oncogenic mutation AND MET:Amplification, NF1:Deletion AND MET:Amplification	Malignant peripheral nerve sheath tumor	Capmatinib; Capmatinib + Trametinib	NF1-MET MPNST are sensitive to capmatinib and/or trametinib in transgenic mouse models.	29720369
GIMR	2021-04-20	FL	4	NF1+SUZ12	NF1:deletion AND SUZ12:deletion	Malignant peripheral nerve sheath tumor	Trametinib	Case report of an exception responder to trametinib (complete response), with tumour harbouring biallelic deletion of NF1 and SUZ12.	33580196
GIMR	2020-11-26	FL	4	NF1+SUZ12	NF1:Loss-of-function mutations AND SUZ12:Loss-of-function mutations	Malignant peripheral nerve sheath tumor	Mirdametinib + JQ1	Preclinical study. Loss of PRC2 component SUZ12 sensitizes cancers with NF1 mutations to BRD4-based therapies by amplifying Ras-driven transcription.	25119042
GIMR	2020-10-08	FL	4	NF2	Loss-of-function mutations	Urothelial carcinoma	Everolimus + Docetaxel	Case report. Exceptional response observed in urothelial carcinoma bearing an NF2 mutation when treated with everolimus in combination with taxane.	25630452
GIMR	2024-09-10	FL	4	NF2	Loss-of-function mutations, deletion	Mesothelioma	VS-4718	Preclinical study. Nf2 deficiency predicts sensitivity toFAK inhibitor in cell lines and MPM xenograft models, particularly in ALDH-positive cancer stem cells.	24848258
GIMR	2023-05-05	FL	4	NF2	Oncogenic mutations	Mesothelioma; Sarcoma	VT3989	NCT04665206. Phase 1. N=67. Responders (2 refractory mesothelioma and 1 NF2 mutant sarcoma) were seen with response by targeting the Hippo-YAP-TEAD pathway.	10.1158/1538-7445.AM2023-CT006
GIMR	2024-09-24	FL	4	NF2	Oncogenic mutations	Solid tumours	IAG933	Preclinical study. The direct disruptor of YAP-TEAD interface showed anti-tumor activity in Hippo-driven mesothelioma xenografts and extended to larger tumor indications, including lung, pancreatic, and colorectal cancer, with durable responses.	38565920
GIMR	2023-06-28	FL	4	NF2	Oncogenic mutations, Deletion	Mesothelioma	VT104	Preclinical study. Small molecule inhibitors of TEAD auto-palmitoylation selectively inhibit proliferation and tumor growth of NF2-deficient mesothelioma, providing a potential therapeutic strategy for targeting the Hippo-YAP pathway in YAP-driven cancers.	33850002
GIMR	2022-04-09	FL	4	NF2	Oncogenic mutations, Truncating mutations	Papillary renal cell carcinoma; Sarcomatoid renal cell carcinoma	Cabozantinib + Nivolumab	Phase 2. NCT03635892. Single arm trial in non-clear cell renal cell carcinomas with ORR of 48%. Responses were seen in 10 of 12 patients with either NF2 or FH mutations. In exploratory biomarker analysis, NF2 mutations were associated with response with Cabozantinib and Nivolumab (5 of 6 cases).	35298296
GIMR	2026-03-04	FL	4	NOTCH1	Oncogenic mutations	Oesophageal squamous cell carcinoma	Tislelizumab	Biomarker analysis. Phase 3. RATIONALE-302. NCT03430843. In advanced/metastatic ESCC with NOTCH1 mutation, tislelizumab versus chemotherapy showed longer OS (18.4 months vs 5.3 months; HR, 0.35). IFN-I signatures positively associated with OS benefit, B-cell and neutrophil signatures predicted unfavorable OS.'	40179324
GIMR	2021-06-26	FL	4	NOTCH1	Oncogenic mutations, Alterations	Adenoid cystic carcinoma	CB-103	Phase 1. NCT03422679. First-in-class CSL-NICD transcription factor complex inhibitor. SD as best response observed in 10 ACC patients (8 with NOTCH alterations). Two case of adenoid cystic carcinoma had prolonged disease control.	10.1200/JCO.2021.39.15_suppl.3020
SuboKB	2020-04-16	FL	4	NOTCH1	Oncogenic mutations, Overexpression	Solid tumours	MRK003	Preclinical study. NOTCH1 mutations and expression levels of HES4 are identified as biomarkers predictive of response to gamma-secretase inhibitor (GSI) in triple-negative breast cancer and adenoid cystic carcinoma.	25104330
SuboKB	2020-04-16	FL	4	NOTCH2	Gain-of-function mutations	Glioblastoma	MRK003	Pre-clinical study. NOTCH pathway blockade using gamma-secretase inhibitors depleted CD133-positive glioblastoma stem cells, inhibited neurosphere growth, and prolonged survival in xenograft models.	19904829
SuboKB	2020-04-16	FL	4	NOTCH3	Overexpression	Non-small cell lung cancer	MRK003	Preclinical study. Gamma-secretase inhibitor MRK-003 inhibited Notch3 signaling, reduced proliferation, and induced apoptosis in lung cancer cell lines in vitro and in vivo.	17804716
GIMR	2020-04-25	FL	4	NOTCH3	Overexpression	Pancreatic adenocarcinoma	Tarextumab	Note negative trial in SCLC (NCT01859741). Drug development discontinued	25934888
GIMR	2024-02-26	FL	4	NRAS	G12C	Solid tumour	Sotorasib; JQD443; RM-018	Preclinical study. Sotorasib is a potent NRASG12C inhibitor, more potent than KRASG12C (5-fold) in vitro. In addition, sotorasib is also a HRASG12C inhibitor. This was demonstrated by the clinical response of a patient with NRASG12C colorectal cancer treated with sotorasib and panitumumab.	38236605
GIMR	2023-05-05	FL	4	NRAS	G12S, Q61K	Melanoma	BGB-3245	Phase 1. NCT04249843. Response seen in a patient post-BRAF/MEK inhibitor	10.1158/1538-7445.AM2023-CT031
GIMR	2023-05-05	FL	4	NRAS	Oncogenic mutations	Melanoma	Exarafenib	Phase 1/1b. NCT04913285. N=52. Exarafenib, a pan-RAF inhibitor, demonstrated preliminary clinical activity with 18% partial response and 47% stable disease in 34 patients across all dose levels with post-baseline tumor assessment.	10.1158/1538-7445.AM2023-CT032
GIMR	2022-01-15	FL	4	NRAS	Oncogenic mutations	Solid tumours	SCH772984	Preclinical study. SCH772984, a novel ERK1/2 inhibitor, showed activity in models with BRAF, NRAS, or KRAS mutations and effectively inhibited MAPK signaling in BRAF or MEK inhibitor-resistant models.	23614898
POTTR	2020-04-16	FL	4	NRAS	Oncogenic mutations	Solid tumours	Ulixertinib; LY3214996; LTT462; Ravoxertinib	ERK inhibitors	29431672, 29247021, 10.1200/JCO.2019.37.15_suppl.3001
GIMR	2025-06-11	FL	4	NRAS	Oncogenic mutations, L95H	Solid tumours	BI-2493; BI-2865	Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models.	37258666
GIMR	2025-06-10	FL	4	NRAS	Q61K	Breast cancer; Melanoma	ADT-007	Preclinical study. ADT-007, a pan-RAS inhibitor, blocks GTP activation of RAS effector interactions and showed antitumor activity and inducing antitumor immunity in GI cancer models with selective targeting of mutant or activated RAS cells.	39700396
GIMR	2020-10-30	FL	4	NRAS	Q61K	Neuroblastoma	SHP099 + Trametinib; SHP099 + Ulixertinib	Cell line study showed that NB cell line is sensitive to SHP2 inhibition (NRAS WT) but resistant to in vivo model with NRAS Q61K. Combining SHP2i with MEKi or ERKi reversed the resistance.	32586982
GIMR	2023-05-05	FL	4	NRAS	Q61K	Non-small cell lung cancer	Lifirafenib + Mirdametinib	Phase 1b. NCT03905148. ORR 15/54 (28%) in efficacy-evaluable patients. 	10.1158/1538-7445.AM2023-CT033
GIMR	2024-05-27	FL	4	NRAS	Q61R, Q61	Solid tumour	NST-628	Preclinical study. NST-628, a pan-RAF-MEK molecular glue, demonstrated broad activity in cell line and PDX models with MAPK pathway alterations.	38588399
GIMR	2021-06-07	FL	4	NRAS	Q61R, Q61S	Melanoma	Belvarafenib	NCT02405065, NCT03118817	33953400
GIMR	2021-12-17	FL	4	NRG1	CD74-NRG1 fusion	Non-small cell lung cancer	GSK2849330	Phase 1. NCT01966445. Single responder with durable response. 	34132450
GIMR	2021-12-29	FL	4	NRG1	DOC4-NRG1 fusion, CLU-NRG1 fusion	Solid tumours	Tarloxotinib	Cell line and xenograft studies. Tarloxotinib-E inhibits MDA-MB-175VIII cell model harboring DOC4-NRG1 fusion, and a xenograft model harbouring CLU-NRG1 fusion.	33355298
GIMR	2020-05-31	FL	4	NRG1	Fusion	Solid tumours	Zenocutuzumab	Case series and preclinical study. MCLA-128, a bispecific HER2/3 antibody, showed clinical responses in patients with NRG1 fusion-positive cancers, including pancreatic ductal adenocarcinoma and non-small cell lung cancer, by inhibiting ligand-driven activation of the HER3 pathway.	10.1158/1535-7163.TARG-19-PR02
GIMR	2024-12-06	FL	4	NRG1	Fusion, CD74-NRG1 fusion, CLU-NRG1 fusion, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, APP-NRG1 fusion	Solid tumours	Zenocutuzumab	Preclinical and case series study. Zenocutuzumab, a HER2xHER3 bispecific antibody, showed effectiveness in NRG1 fusion-positive cancer models and patients. In a cohort of 3 patients with NRG1 fusion-positive metastatic cancer, 2 achieved rapid and durable responses: 2 pancreatic cancer patients with ATP1B1-NRG1 fusion and 1 non-small cell lung cancer patient with CD74-NRG1 fusion.	35135829
GIMR	2022-05-17	FL	4	NRG1	Fusion, DOC4-NRG1 fusion, SLC3A2-NRG1 fusion, CD74-NRG1 fusion	Breast cancer; Non-small cell lung cancer; Ovarian cancer; Solid tumours	Seribantumab	Preclinical study. Seribantumab effectively inhibits growth of patient-derived and isogenic cell line and xenograft models with oncogenic NRG1 fusions in breast, lung, and ovarian cancers, inducing tumor regression by blocking activation of ERBB family members and downstream signaling.	33824166
GIMR	2021-03-31	FL	4	NRG1	Fusion; CD74-NRG1 fusion; POMK-NRG1 fusion; APP-NRG1 fusion	Non-small cell lung cancer; Solid tumours	Afatinib	Case series. Partial response seen in patients with fusion in two NSCLC, one colorectal cancer, and one pancreatic cancer treated with afatinib. Two NSCLC patients treated with afatinib were seen with prolonged responses.	10.1200/JGO.2019.5.suppl.110
GIMR	2021-03-31	FL	4	NRG1	Fusion; CD74-NRG1 fusion; SLC3A2-NRG1 fusion	Non-small cell lung cancer	Afatinib	Case reports. Partial response seen in patients with fusion in two NSCLC with responses of 6 and 10 months respectively.	28502724
GIMR	2021-03-31	FL	4	NRG1	Fusion; CD74-NRG1 fusion; VAMP2-NRG1 fusion; SLC3A2-NRG1 fusion	Solid tumours	Seribantumab		10.1016/S0959-8049(20)31105-9
GIMR	2021-03-31	FL	4	NRG1	Fusion; SDC4-NRG1 fusion; ATP1B1-NRG1 fusion	Non-small cell lung cancer; Cholangiocarcinoma	Afatinib	Case reports. Partial response seen in patients with fusion in two NSCLC.	28950338
GIMR	2021-03-31	FL	4	NRG1	Fusion; SLC3A2-NRG1 fusion	Non-small cell lung cancer	Lumretuzumab + Erlotinib	Case reports. Two patients with invasive mucinous lung adenocarcinoma harboring NRG1 fusion achieved at least 16 weeks of progression-free survival when treated with lumretuzumab, an anti-HER3 antibody, in combination with erlotinib.	30268483
GIMR	2021-06-08	FL	4	NRG1	Fusions	Non-small cell lung cancer	Afatinib	Registry study. NRG1 fusion-positive lung cancers showed varied clinicopathologic features and responded poorly to chemotherapy (ORR 13-14%) and immunotherapy (ORR 0-20%), but afatinib achieved an ORR of 25% regardless of fusion type. CD74-NRG1 and non-CD74-NRG1 have similar ORR (22% and 27% respectively).	34077268
GIMR	2021-06-25	LMKC	4	NRG1	Fusions, ATP1B1-NRG1 fusion	Pancreatic adenocarcinoma	Afatinib	Preclinical study and case series. NRG1 gene fusions were identified in KRAS wild-type pancreatic ductal adenocarcinoma. Two patients with NRG1 fusion-positive tumors treated with afatinib demonstrated significant and rapid response.	31068372
GIMR	2021-05-18	FL	4	NRG1	High mRNA expression	Lung squamous cell carcinoma	Lumretuzumab	Exploratory analysis: ORR was 42.9% in the heregulin-high group with DCR was 100% (7/7 patients). ORR was 0% in the heregulin-low group	31423336
GIMR	2025-04-30	FL	4	NRG1	SDC4-NRG1 fusion	Cholangiocarcinoma	Zongertinib	Preclinical study & Case series. Zongertinib, a covalent HER2 TKI, exhibits antitumor activity in HER2-dependent NSCLC xenografts and induces objective responses in HER2-driven cancers, including SDC4-NRG1 fusion-positive cholangiocarcinoma and HER2 V777L-mutant breast cancer. 	39248702
GIMR	2023-04-20	FL	4	NRG1	SLC3A2-NRG1 fusion	Breast cancer	Zenocutuzumab	Case report. Sustained tumor regression observed with Zenocutuzumab, a bispecific antibody targeting HER2/HER3 signaling, in NRG1 fusion-positive, estrogen receptor-positive breast cancer.	35977350
GIMR	2021-03-24	FL	4	NTRK1	Amplification	Oesophageal squamous cell carcinoma	Larotrectinib	Case report. A patient with metastatic esophageal carcinoma harboring NTRK1 gene amplification showed significant tumor shrinkage and decrease in tumor markers after treatment with larotrectinib, suggesting potential efficacy of larotrectinib in cases with NTRK gene amplification.	32323889
GIMR	2022-06-04	FL	4	NTRK1	Fusion	Solid tumours	ICP-723	Phase 1/2 trial. NCT04685226. ICP-723, a next-generation pan-TRK inhibitor, showed encouraging efficacy in patients with NTRK gene fusion positive tumors with an ORR of 66.7% (4 PR) and DCR of 100%, including intracranial activity in a patient with brain metastasis, and demonstrated activity against various tumor types.	10.1200/JCO.2022.40.16_suppl.3106
GIMR	2020-04-30	FL	4	NTRK1	Fusion	Solid tumours	Taletrectinib	Preclinical study. DS-6051b induces growth inhibition in NTRK-rearranged cancers in vitro and in vivo.	31399568
GIMR	2022-01-21	FL	4	NTRK1	Fusion, G595R	Solid tumours	Repotrectinib	Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models.	30093503
GIMR	2025-02-17	FL	4	NTRK1	LMNA-NTRK1 fusion, A608D	Solid tumours	Larotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	4	NTRK1	LMNA-NTRK1 fusion, F589L, V573M, A608D	Solid tumours	Repotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	4	NTRK1	LMNA-NTRK1 fusion, V573M, A608D	Solid tumours	Selitrectinib, Zurletrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2021-01-31	FL	4	NTRK1	TPR-NTRK1 fusion	Pancreatic adenocarcinoma	Entrectinib	Two case reports. KRAS wild-type PDAC. One PR. 	10.1200/PO.18.00039
GIMR	2025-02-17	FL	4	NTRK2	ETV6-NTRK2 fusion, V689M	Solid tumours	Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2022-06-04	FL	4	NTRK2	Fusion	Solid tumours	ICP-723	Phase 1/2 trial. NCT04685226. ICP-723, a next-generation pan-TRK inhibitor, showed encouraging efficacy in patients with NTRK gene fusion positive tumors with an ORR of 66.7% (4 PR) and DCR of 100%, including intracranial activity in a patient with brain metastasis, and demonstrated activity against various tumor types.	10.1200/JCO.2022.40.16_suppl.3106
GIMR	2020-04-30	FL	4	NTRK2	Fusion	Solid tumours	Taletrectinib	Preclinical study. DS-6051b induces growth inhibition in NTRK-rearranged cancers in vitro and in vivo.	31399568
GIMR	2022-01-21	FL	4	NTRK2	Fusion, G639R	Solid tumours	Repotrectinib	Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models.	30093503
GIMR	2021-08-19	FL	4	NTRK2	KANK1-NTRK2 fusion	Ependymoma	Larotrectinib	Case report. Recurrent disseminated ependymoma harboring a KANK1-NTRK2 fusion experienced a durable response to larotrectinib, a TRK inhibitor, with significant clinical and radiographic improvement, highlighting the importance of integrated genomic profiling in pediatric CNS tumors with NTRK fusions.	34651095
GIMR	2025-02-17	FL	4	NTRK3	ETV6-NTRK3 fusion	Solid tumours	Larotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	4	NTRK3	ETV6-NTRK3 fusion, F617L, G623E, G696A	Solid tumours	Repotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	4	NTRK3	ETV6-NTRK3 fusion, G623E	Solid tumours	Selitrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	4	NTRK3	ETV6-NTRK3 fusion, G623E, G696A	Solid tumours	Zurletrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2022-06-04	FL	4	NTRK3	Fusion	Solid tumours	ICP-723	Phase 1/2 trial. NCT04685226. ICP-723, a next-generation pan-TRK inhibitor, showed encouraging efficacy in patients with NTRK gene fusion positive tumors with an ORR of 66.7% (4 PR) and DCR of 100%, including intracranial activity in a patient with brain metastasis, and demonstrated activity against various tumor types.	10.1200/JCO.2022.40.16_suppl.3106
GIMR	2020-04-30	FL	4	NTRK3	Fusion	Solid tumours	Taletrectinib	Preclinical study. DS-6051b induces growth inhibition in NTRK-rearranged cancers in vitro and in vivo.	31399568
GIMR	2022-01-21	FL	4	NTRK3	Fusion, G623E, G623R	Solid tumours	Repotrectinib	Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models.	30093503
GIMR	2021-02-18	FL	4	NTRK3	Protein expression	Medulloblastoma	Entrectinib	In vitro and in vivo DSRCT models with NTRK3 expression. Entrectinib reduces growth of cells.	33229458
GIMR	2022-01-15	FL	4	NUTM1	Protein expression	NUT carcinoma	Birabresib	Phase 1. NCT02259114. 3/10 patients had partial response. Trial entry criteria was determined by ectopic expression of NUT protein or confirmed BRD-NUT translocation by FISH	29733771
GIMR	2021-06-09	FL	4	PALB2	Loss-of-function mutations	Breast cancer	Olaparib	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2020-04-25	FL	4	PALB2	Loss-of-function mutations	Pancreatic adenocarcinoma	Cisplatin + Gemcitabine; Cisplatin + Gemcitabine + Veliparib	Phase 2 trial. Significant responses observed in patients with pancreas adenocarcinoma and germline BRCA/PALB2 mutation, with Response Rate (RR) of 74.1% and 65.2% in patients treated with cisplatin and gemcitabine with or without veliparib, respectively.	31976786
GIMR	2020-04-25	FL	4	PALB2	Loss-of-function mutations	Pancreatic adenocarcinoma	Talazoparib	Phase 1 trial. NCT01286987. Talazoparib demonstrated antitumour activity in a single case of PALB2 mutation amongst 13 pancreatic cancer patients who showed partial responses.	28242752
GIMR	2022-03-10	FL	4	PALB2	Loss-of-function mutations (germline)	Pancreatic adenocarcinoma	Olaparib	Phase 2 single arm study. NCT02677038 and NCT02511223. Single responder to olaparib (of two patients) with DOR 3.9 months.	33662100
GIMR	2024-11-13	FL	4	PALB2	Oncogenic mutations	Ovarian cancer; Prostate cancer; Pancreatic cancer	HRS-1167	Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer).	10.1200/JCO.2024.42.16_suppl.3154
GIMR	2020-05-05	FL	4	PALB2	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 4 patient. Subgroup not compared.	32343890, 32955174
GIMR	2020-04-25	FL	4	PALB2	Oncogenic mutations	Prostate cancer	Rucaparib	Phase 2 TRITON2 trial. NCT02952534. Responses to Rucaparib observed in patients with PALB2 alterations, among other DDR-associated genes, but limited responses seen in patients with ATM, CDK12, or CHEK2 alterations.	32086346
GIMR	2021-09-09	FL	4	PALB2	Oncogenic mutations	Prostate cancer	Talazoparib	Phase 2 TALAPRO-1 trial. NCT03148795. Talazoparib demonstrated antitumour activity in metastatic castration-resistant prostate cancer with DDR-HRR gene alterations, achieving an objective response rate of 29.8% (31/104) in patients with measurable soft-tissue disease. In the PALB2 subgroup (N=4), 1 confirmed partial response was observed.	34388386
GIMR	2022-03-12	FL	4	PALB2	Oncogenic mutations (germline)	Breast cancer	Olaparib	Case report. PALB2 c.18G>T with ARID1A Q1409*. Treatment with single-agent olaparib yielded DOR of 11 months.	32728620
GIMR	2020-04-25	FL	4	PALB2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	FOLFIRINOX	Retrospective observational study. Patients with PALB2 mutation (n=4), along with BRCA1 and BRCA2 mutants, had a high ORR (58%) and prolonged rwPFS (10.1 months) when treated with platinum-based chemotherapy.	31787751
GIMR	2021-03-16	FL	4	PALB2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Olaparib	Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. One responder seen in PALB2 germline mutation.	33662100
GIMR	2025-10-19	FL	4	PALB2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	SNV1521	Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities.	ESMO25.923MO
GIMR	2021-05-24	FL	4	PBRM1	Loss-of-function mutations	Melanoma	Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody	Inactivation of genes encoding components of the PBAF complex complex sensitised mouse B16F10 melanoma cells to killing by T cells. 	29301958
GIMR	2022-11-28	FL	4	PBRM1	Loss-of-function mutations, Loss of protein expression	Solid tumours	Olaparib; Rucaparib; Talazoparib	Preclinical study. PBRM1 deficiency is synthetic lethal with DNA repair inhibitors, with PARP and ATR inhibitors showing efficacy in PBRM1-defective cancer cells, particularly in clear cell renal cell carcinomas, due to elevated replication stress, micronuclei, and R-loops.	33888468
GIMR	2021-05-24	FL	4	PBRM1	Loss-of-function mutations; Oncogenic mutations	Renal cell carcinoma; Solid tumours	Talazoparib; Olaparib; Rucaparib; Berzosertib; Ceralasertib	PARP and ATR inhibitors were shown to be synthetically lethal in PBRM1-deficient tumours in cell line and Xenograft models.	33888468
GIMR	2022-02-09	FL	4	PBRM1	Oncogenic mutations	Pancreatic adenocarcinoma	Pembrolizumab; Durvalumab; Atezolizumab; Nivolumab	Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.	34375311
POTTR	2020-04-16	FL	4	PBRM1	Oncogenic mutations	Solid tumours	BET inhibitor	Review article	28426098
GIMR	2022-10-04	FL	4	PBRM1	Oncogenic mutations	Thymic carcinoma; Thymoma	Avelumab + Axitinib	Phase 2. PECATI trial. NCT04710628. Risk ratio of response to the combination in patients with PBRM1 mutation was 4.0	36096156
GIMR	2022-10-04	FL	4	PBRM1	Truncating mutations	Renal cell carcinoma	Nivolumab	Exploratory analysis of CheckMate025 data. Odds ratio of response and clinical beneift to Nivolumab were higher (2.34 and 2.14 respectively) in patients with PBRM1 mutations. RCC with PBRM1 mutation was associated with increased PFS (5.6 v 2.9 months) and OS (27.9 vs 20.9 months) respectively.	31486842
POTTR	2020-04-16	FL	4	PDCD1LG2	Amplification	Solid tumours	Anti-PD-1 monoclonal antibody	Case report. A patient with metastatic colon cancer and amplification of CD274 (PD-L1) and PDCD1LG2 (PD-L2) showed a durable response to nivolumab, but acquired resistance developed through outgrowth of cells lacking these amplifications, suggesting that combination therapies targeting both amplified and non-amplified cell populations might be more effective.	35135174
GIMR	2025-07-07	FL	4	PDGFRA	D842V	Gastrointestinal stromal tumour	Avapritinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2020-04-23	FL	4	PDGFRA	D842V	Gastrointestinal stromal tumour	Avapritinib; Crenolanib; Midostaurin	Preclinical studies and case reports. Type II c-Kit inhibitors are resistant to KIT D816 and PDGFR842V mutations	29093181
GIMR	2020-05-15	FL	4	PDGFRA	D842V	Gastrointestinal stromal tumour	Ripretinib	Preclinical study. Ripretinib, a switch-control kinase inhibitor, demonstrated efficacy against a broad spectrum of oncogenic and drug-resistant KIT and PDGFRA variants, particularly activation loop mutations, in cancer models.	31085175
GIMR	2022-01-25	FL	4	PDGFRA	FIP1L1-PDGFR fusion, T674I	Chronic eosinophilic leukaemia	Sorafenib	Cell line study. In transformed Ba/F3 cells, sorafenib inhibited cell growth in models that harbour FIPL1-PDGFRA and PDGFRA T674I.	16645167
GIMR	2021-01-25	FL	4	PDGFRA	I843_D846del	Gastrointestinal stromal tumour	Sorafenib	Case report. Durable response to Sorafenib (12.5 years) following progression on both Sunitinib and Nilotinib.	34949997
GIMR	2023-01-18	FL	4	PDGFRA	P567P, I843del, D842del, R560del, V516D, I843_D846del, Exon 12 mutation, Exon 18 deletion	Gastrointestinal stromal tumour	Imatinib	Retrospective study. Responses (5/7) were seen in patients with Non-D842V exon 18 mutations and exon 12 mutations.	26130666
GIMR	2022-01-25	FL	4	PDGFRA	V561D, D842_H845del	Gastrointestinal stromal tumour	Imatinib; Sorafenib; Sunitinib	Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842.	22665524
GIMR	2022-01-25	FL	4	PDGFRA	V561D, N659K, D842Y, D842_I843delinsIM, D842_H845del, I843_H846del, Exon 18 deletion, Exon 12 mutation, Exon 14 mutation	Gastrointestinal stromal tumour	Imatinib	Preclinical study. Various PDGFRA mutations showed different in vitro sensitivity to imatinib, with exon 12 and 14 mutations being imatinib-sensitive, while most exon 18 mutations, particularly D842V, were imatinib-resistant, except for D842Y, D846Y, N848K, Y849K, and HDSN845-848P.	15928335
GIMR	2023-01-18	FL	4	PDGFRA	W559_R560del	Gastrointestinal stromal tumour	Imatinib; Sunitinib	Case report. A patient with gastrointestinal stromal tumor harboring a rare exon 12 PDGFRA mutation showed a dramatic response to sunitinib after relapsing on imatinib, suggesting sunitinib as a potential treatment option for this rare molecular subtype.	26396737
GIMR	2023-07-31	FL	4	PGR	Protein expression	Granulosa cell tumour; Low-grade serous ovarian carcinoma; Endometrioid endometrial cancer	Onapristone	Phase 2. NCT03909152. ONA-XR. in PR+ recurrent GCT (cohort 1), LGSOC (cohort 2), and EEC (cohort 3). No objective responses were observed in cohorts 1-3. In cohort 2 (LGSOC), median PFS was 4.4 months, and CBR was 50%. In cohort 1 (GCT), median PFS was 3.5 months, 6-month PFS rate was 30%, and 12-month PFS rate was 20%. CBR was 36%. ONA-XR was well-tolerated.	10.1200/JCO.2022.40.16_suppl.5521
GIMR	2020-11-15	FL	4	PIK3CA	E542K and E453, E542K and E726K, E542K and M1043, E545K and E453, E545K and E726, E542K and M1043, H1047R and E453, H1047R and E726K, E543Q and H1047R, E726K and H1047R	Breast cancer	Taselisib; Alpelisib; Inavolisib	Double PIK3CA mutations in cis increased sensitivity to PI3K alpha inhibitors.	31699932
GIMR	2024-09-15	FL	4	PIK3CA	H1047R, E453K, E542K	Breast cancer	RLY-2608	Phase 1. NCT05216432. RLY-2608. Objective responses was seen in 2 patients with advanced hormone receptor-positive breast cancer and PIK3CA mutations.	37916956
GIMR	2020-04-16	FL	4	PIK3CA	Kinase domain mutations	Solid tumours	Ipatasertib	Preclinical study. GDC-0068, a selective Akt inhibitor, showed antitumor activity in human cancer cells with markers of Akt activation, including PTEN loss and PIK3CA kinase domain mutations, and enhanced antitumor activity of chemotherapeutic agents.	23287563
GIMR	2020-11-15	FL	4	PIK3CA	Oncogenic mutations	Breast cancer	Buparlisib + Tamoxifen	PIKTAM trial. ORR 40% but stoped prematurely due to toxicity	32352244
GIMR	2020-04-16	FL	4	PIK3CA	Oncogenic mutations	Breast cancer	GDC-0077	Phase 1a dose escalation study. NCT03006172. N=20. GDC-0077, a p110α-selective and mutant-degrading PI3K inhibitor, showed manageable safety profile, linear PK, and preliminary anti-tumor activity with 25% partial response rate and 45% clinical benefit rate in patients with PIK3CA-mutant solid tumors.	10.1158/1538-7445.SABCS19-OT1-08-04
GIMR	2021-03-31	FL	4	PIK3CA	Oncogenic mutations	Breast cancer	Ipatasertib + Paclitaxel	HR-positive disease. IPATunity130 Cohort B. ORR 47% in both ipatasertib and placebo arms but there was no significant difference in median PFS (ipatasertib vs placebo: 9.2 vs 8.5 mo). Ongoing follow-up.	10.1016/j.annonc.2020.08.385
GIMR	2020-04-16	FL	4	PIK3CA	Oncogenic mutations	Solid tumours	Alpelisib	Phase Ia study. NCT01219699. Alpelisib showed preliminary activity in PIK3CA-altered solid tumors with ORR 6%, CBR 58%, and median PFS of 5.5 months in estrogen receptor-positive breast cancer.	29401002
GIMR	2021-06-18	FL	4	PIK3CA	Oncogenic mutations	Solid tumours	Sapanisertib + Metformin		10.1200/JCO.2021.39.15_suppl.3017
GIMR	2022-09-12	FL	4	PIK3CA	Oncogenic mutations, E545A, E545K, E542K	Solid tumours	CYH33		10.1016/j.annonc.2021.01.048
GIMR	2022-09-14	FL	4	PIK3CA	Oncogenic mutations, H1047R	Metaplastic breast carcinoma	Buparlisib	Case report from BELLE-4. Confirmed partial response for 17 months in total. 	30577988
GIMR	2023-06-22	FL	4	PIK3R1	Oncogenic mutations, Deletion	Prostate cancer	Ipatasertib; MK-2206	Cell line study. PIK3R1-mutant and knockdown prostate cancer cells are sensitive to AKT inhibitors, which have shown sensitivity of to the AKT kinase inhibitors.	35670774
GIMR	2021-08-04	FL	4	PMS2	K706Sfs	Glioblastoma	Nivolumab	Case series. Germline PMS2 homozygous mutant. All tumours are hypermutants with ultrahigh TMB. Two cases (paediatric) had significant clinical and radiological responses to single agent Nivolumab.	27001570
SuboKB	2020-04-16	FL	4	PMS2	Loss-of-function mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Check MSI IHC	26895986
GIMR	2020-06-29	FL	4	POLD1	Loss of protein expression	Colorectal adenocarcinoma	Berzosertib	ATR inhibitor. Cell line study	26755646
GIMR	2021-11-22	FL	4	POLD1	Oncogenic mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Retrospective variant registry analysis showing POLE/POLD1 mutants have higher ORR (35%) versus wildtype (20%) when treated with immune checkpoint blockades.	33569431
GIMR	2021-11-22	FL	4	POLE	Oncogenic mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Retrospective variant registry analysis showing POLE/POLD1 mutants have higher ORR (35%) versus wildtype (20%) when treated with immune checkpoint blockades.	33569431
SuboKB	2020-05-31	FL	4	POLE	Oncogenic mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Clinical cohort studies	31415061, 10.1200/JCO.2020.38.15_suppl.3008, 27486176
GIMR	2020-11-15	FL	4	POLE	P286R	Colorectal adenocarcinoma	Pembrolizumab	Case report. A patient with POLE-mutated colorectal cancer and ultra-high tumor mutation burden experienced a complete and sustained response to pembrolizumab.	10.1200/PO.18.00214
GIMR	2020-12-11	FL	4	POLE	P286R, T323A	Uterine carcinosarcoma	Pembrolizumab	Case report. The case also had a high tumour mutational burden.	29386312
GIMR	2025-04-25	FL	4	POU2F3	Protein expression	Small-cell lung cancer	FHD-609; FHD-286	Preclinical study. Mammalian SWI/SNF complex activity in small cell lung cancer, specifically the POU2F3-positive subtype (SCLC-P), represents a targetable dependency. BRD9 degrader (FHD-609) and SMARCA4/2 inhibitor (FHD-286) independently inhibit tumor growth and improve survival in POU2F3-positive SCLC xenograft models, with enhanced efficacy when combined with first-line chemotherapy.	39029464
GIMR	2022-04-04	FL	4	PPM1D	Loss-of-function mutations	Diffuse Intrinsic Pontine Glioma	Olaparib	Preclinical study. PPM1D-mutant DIPG cells showed sensitization to PARP inhibitor Olaparib when targeted with PPM1D inhibitor GSK2830371, impairing homologous recombination-mediated DNA repair.	32229503
GIMR	2021-04-14	FL	4	PRKDC	Oncogenic mutations, Loss-of-function mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	CT26 animal model with PRKDC-KO showed enhanced efficacy to anti-PD-1 monoclonal antibody.	32238472
GIMR	2021-04-14	FL	4	PRKDC	Oncogenic mutations, Loss-of-function mutations	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Retrospective analysis showed that PRKDC mutation is associated with better response to ICI.	32502294
POTTR	2020-04-16	FL	4	PSMA	Protein expression	Prostate cancer	BAY2010112	Preclinical studies. Bispecific antibodies and Fab conjugates targeting PSMA and CD3 demonstrated potent and selective activity against prostate cancer cell lines, with effective T cell redirection and cytotoxicity, and induced regression of human prostate cancer xenografts in mice.	23041545, 29126850
POTTR	2020-04-16	FL	4	PSMA	Protein expression	Prostate cancer	Bispecific PSMA/CD3 antibody	Preclinical study. A PSMA-targeting CD3 bispecific antibody induced antitumor responses that were enhanced by 4-1BB costimulation, leading to durable antitumor responses and T-cell memory in preclinical solid tumor models.	32184296
SuboKB	2020-04-25	ST	4	PTCH1	Loss-of-function mutations	Medulloblastoma	Sonidegib; Vismodegib	Preclinical study. RAS/MAPK activation drives resistance to Smo inhibition and enhances metastatic behavior in Shh pathway-dependent tumors, with evidence of RAS/MAPK-driven tumor evolution in Smo inhibitor-treated BCC patients.	26130651
GIMR	2020-06-30	FL	4	PTCH1	Oncogenic mutations	Medulloblastoma	Vismodegib	Case report. A 26-year-old man with metastatic medulloblastoma refractory to multiple therapies showed rapid, transient tumor regression and symptom reduction after treatment with GDC-0449 with molecular analysis indicating hedgehog pathway activation and PTCH1 mutation.	19726761
SuboKB	2020-04-16	ST	4	PTCH1	Oncogenic mutations	Solid tumours	Sonidegib; Vismodegib	MyPathway; MoST	29320312, NCT02091141
GIMR	2022-03-04	FL	4	PTCH1	Oncogenic mutations, Truncating mutations	Basal cell carcinoma; Medulloblastoma	Itraconazole; Arsenic trioxide	Preclinical study demonstrating in vitro activity of itraconazole 	23291299
GIMR	2020-06-11	FL	4	PTEN	Loss of protein expression	Renal cell carcinoma	Everolimus	Against Sunitinib HR 2.5	29390043
GIMR	2020-05-23	FL	4	PTEN	Loss-of-function mutations	Breast cancer	Everolimus	Exploratory biomarker analysis of BOLERO-1 and BOLERO-3 trials. Everolimus associated with improved PFS in patients with PIK3CA mutations (HR, 0.67), PTEN loss (HR, 0.54), or hyperactive PI3K pathway (HR, 0.67).	27091708
GIMR	2025-03-16	FL	4	PTEN	Loss-of-function mutations	Prostate cancer	Capivasertib + Docetaxel	Preclinical study. Capivasertib combined with docetaxel demonstrated enhanced anti-tumor activity in prostate cancer models by inhibiting AKT-mediated survival mechanisms, particularly in PTEN-null cells.	38396173
GIMR	2020-04-16	FL	4	PTEN	Loss-of-function mutations	Solid tumours	Ipatasertib	Preclinical study. GDC-0068, a selective Akt inhibitor, showed antitumor activity in human cancer cells and xenograft models, with sensitivity correlated to PTEN loss and high-basal phospho-Akt levels.	23287563
GIMR	2021-06-18	FL	4	PTEN	Loss-of-function mutations	Solid tumours	Sapanisertib + Metformin	Phase 1 study. NCT03017833. Sapanisertib + metformin showed anti-tumor activity in patients with advanced solid tumors harbouring PTEN mutations and AKT/mTOR pathway alterations, with 4/30 patients achieving partial response, mostly with PTEN mutations.	10.1200/JCO.2021.39.15_suppl.3017
GIMR	2023-11-22	FL	4	PTEN	Loss-of-function mutations, deletion	Acute myeloid leukaemia	Talazoparib		10.1182/blood-2021-146694
GIMR	2021-03-31	FL	4	PTEN	Oncogenic mutations	Breast cancer	Ipatasertib + Paclitaxel	HR-positive disease. IPATunity130 Cohort B. ORR 47% in both ipatasertib and placebo arms but there was no significant difference in median PFS (ipatasertib vs placebo: 9.2 vs 8.5 mo). Ongoing follow-up.	10.1016/j.annonc.2020.08.385
GIMR	2020-04-16	FL	4	PTEN	Oncogenic mutations	Triple-negative breast cancer	AZD8186	Preclinical data only	10.1158/1538-7445.AM2018-5802
POTTR	2020-04-16	FL	4	PTPN11	Oncogenic mutations	Solid tumours	Ulixertinib; LY3214996; LTT462; Ravoxertinib	ERK inhibitors	29431672, 29247021, 10.1200/JCO.2019.37.15_suppl.3001
GIMR	2020-04-16	FL	4	PTPN11	Oncogenic mutations, E72K	Histiocytosis	Trametinib	Case report. Multifocal histiocytic sarcoma patient showed response to MEK inhibition with trametinib and tyrosine kinase inhibition with imatinib.	29097496
GIMR	2021-07-04	FL	4	RAD21	Oncogenic mutations	Myelodysplastic syndrome; Acute myeloid leukaemia	Talazoparib	Cell line study. Inactivation of SMC3 or RAD21, and STAG2 mutations, increase sensitivity to PARP inhibition.	33351783
GIMR	2021-06-09	FL	4	RAD50	Loss-of-function mutations	Breast cancer	Olaparib	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2020-10-20	FL	4	RAD50	Oncogenic mutations; Deletions	Ovarian cancer	Olaparib; Rucaparib	Preclinical study. RAD50 copy number deletion is associated with BRCAness and improved response to PARP inhibitors in BRCA wild-type ovarian cancer, with decreased RAD50 expression leading to enhanced sensitivity to cisplatin and olaparib.	27016230
GIMR	2025-05-30	FL	4	RAD51	Loss of protein expression	Uterine leiomyosarcoma	Olaparib + Temozolomide	Phase 2 study. NCI Protocol 10250. N=22. Olaparib + temozolomide showed an ORR of 27% and mPFS of 6.9 months in advanced uterine leiomyosarcoma. 50% of tumors were homologous recombination-deficient by RAD51 assay, with prolonged mPFS (11.2 vs 5.4 months) in RAD51-deficient tumors. The RAD51 status is determined using a IHC based foci formation assay.	37467452
GIMR	2022-06-19	FL	4	RAD51	Low protein expression	Triple-negative breast cancer	Olaparib + Ceralasertib	Phase 2 plasmaMatch Cohort E. ATM loss, high CCNE1 expresion, and low RAD51 were associated with higher rate of response and PFS.	10.1200/JCO.2022.40.16_suppl.1024
GIMR	2020-05-05	FL	4	RAD51B	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 1 patient in control arm.	32343890, 32955174
GIMR	2021-06-09	FL	4	RAD51C	Loss-of-function mutations	Breast cancer	Olaparib	Cell line (MCF7) synthetic lethal screening using olaparib and specific PARG inhibitor PDD00017273	28254358
GIMR	2023-01-18	FL	4	RAD51C	Low protein expression; No protein expression	Solid tumours	Olaparib	In cell line models, RAD51C-deficient cells are sensitive to olaparib.	23512992
GIMR	2024-11-13	FL	4	RAD51C	Oncogenic mutations	Ovarian cancer; Prostate cancer; Pancreatic cancer	HRS-1167	Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer).	10.1200/JCO.2024.42.16_suppl.3154
GIMR	2020-04-25	FL	4	RAD51C	Oncogenic mutations	Solid tumours	Olaparib	Preclinical study. RAD51C-deficient cancer cells showed increased sensitivity to olaparib, with enhanced G2-M cell-cycle arrest and apoptosis, and RAD51C deficiency may be considered a biomarker for predicting olaparib's antitumor effects.	23512992
GIMR	2022-07-08	FL	4	RAD51C	Oncogenic mutations	Urothelial carcinoma	Durvalumab + Olaparib	Randomised phase 2. BAYOU. NCT03459846. Untreated platinum-ineligible urothelial carcinoma. Primary endpoint was not met (PFS durvalumab + olaparib 4.2 months v durvalumab + placebo 3.5 months). However, in 20% of patient with mutation in predefined 15-gene of homologous recombination repair mutation (HRRm subset), the PFS was longer in olaparib group (5.6 months v placebo: 1.8 months) (predefined secondary endpoint).	35737919
GIMR	2020-07-02	FL	4	RAD51C	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	FOLFIRINOX	Case report. A patient with metastatic pancreatic adenocarcinoma and a germline RAD51C mutation showed a remarkable response to FOLFIRINOX, a platinum-containing chemotherapy regimen.	30151275
GIMR	2023-06-14	FL	4	RAD51C	Oncogenic mutations, Oncogenic mutations (germline)	Ovarian cancer	Camonsertib	Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations.	37277454
GIMR	2023-01-18	FL	4	RAD51C	Promoter methylation	Ovarian cancer	Rucaparib; Niraparib	Preclinical study. RAD51C promoter methylation loss causes PARP inhibitor resistance in high-grade serous ovarian carcinoma PDX models, where a single unmethylated copy of RAD51C is sufficient to drive resistance.	34321239
GIMR	2024-06-02	FL	4	RAD51D	Oncogenic mutations	Ovarian cancer	KSQ-4279 + Olaparib	Phase 1 trial. NCT05240898. N=64. KSQ-4279, a first-in-class USP1 inhibitor, showed acceptable in combination with olaparib or carboplatin in patients with advanced solid tumours and deleterious HRR mutations; disease control rate at 16 weeks was 28%, 40%, and 29% respectively.	10.1200/JCO.2024.42.16_suppl.3005
GIMR	2024-11-13	FL	4	RAD51D	Oncogenic mutations	Ovarian cancer; Prostate cancer; Pancreatic cancer	HRS-1167	Phase 1. NCT05473624. In 24 patients with HRR mutations for tumor response, ORR was 42% (10/24), including (8 ovarian cancer, 1 prostate cancer, and 1 pancreatic cancer).	10.1200/JCO.2024.42.16_suppl.3154
GIMR	2020-05-05	FL	4	RAD51D	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: 1 patient only.	32343890, 32955174
GIMR	2020-04-16	FL	4	RAD51D	Oncogenic mutations	Solid tumours	Olaparib		28588062, 28646019, 10.1200/PO.18.00253
GIMR	2025-10-19	FL	4	RAD51D	Oncogenic mutations (germline)	Ovarian cancer	SNV1521	Phase 1 trial. NCT06220864. N=32. SNV1521, a CNS-penetrant PARP1-selective inhibitor, showed encouraging anti-tumor activity with 5 responses in canonical tumors (PC/BC/OC/PDAC) and was well-tolerated with minimal hematologic toxicities.	ESMO25.923MO
GIMR	2020-05-05	FL	4	RAD54L	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B: Subgroup not compared.	32343890, 32955174
GIMR	2021-01-12	FL	4	RAF1	Fusion; ANO10-RAF1 fusion	Melanoma	Trametinib	Case report. Significant disease response. Duration of response < 6 months	35135096
GIMR	2021-01-12	FL	4	RAF1	Fusion; ATG7-RAF1 fusion	Anaplastic pleomorphic xanthoastrocytoma	Cobimetinib	Case report. Sustained response with complete cytologic response in CSF.	10.1200/PO.18.00298
GIMR	2021-01-12	FL	4	RAF1	Fusion; GOLGA4-RAF1 fusion	Melanoma	Cobimetinib	Case report. A metastatic melanoma patient with a GOLGA4-RAF1 fusion and resistance to anti-CTLA4/anti-PD1 combination immunotherapy showed a profound response to MEK inhibitor therapy, indicating the potential of thorough molecular characterization to identify therapeutic targets in treatment-resistant cancers harbouring specific mutations.	30835257
GIMR	2021-01-12	FL	4	RAF1	Fusion; NFIA-RAF1 fusion	Pilocytic astrocytoma	Trametinib	Case report. Paediatric low-grade glioma. Case report. Stable disease for 12 months.	27810072
GIMR	2021-01-12	FL	4	RAF1	Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion	Low-grade gliomas	LY3009120	Paediatric low-grade gliomas	28806393
GIMR	2021-01-12	FL	4	RAF1	Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion	Low-grade gliomas	Trametinib	Paediatric low-grade gliomas. Response in cell line model but not in xenograft	28806393
GIMR	2022-03-15	FL	4	RAF1	FYCO1-RAF1 fusion	Melanoma	Trametinib	Case report. Partial response for 40 weeks.	33684875
GIMR	2022-03-15	FL	4	RAF1	NFIA-RAF1 fusion	Pilocytic astrocytoma	Trametinib	Case report. Best response at 6 months is stable disease.	27810072
GIMR	2020-04-16	FL	4	RAF1	Oncogenic mutations	Histiocytosis	Trametinib	Preclinical study and case reports. Whole-exome and transcriptome sequencing identified diverse and targetable kinase alterations, including recurrent kinase fusions and mutations, in BRAF(V600E)-wild-type non-Langerhans cell histiocytosis. Treatment with MEK and RAF inhibitors showed response in patients with MAP2K1- and ARAF-mutated non-LCH.	26566875
GIMR	2022-03-15	FL	4	RAF1	QKI-RAF1 fusion	Spindle cell sarcoma	Trametinib	Case report. Duration of response to trametinib 10 months with complete metabolic response on FDG-PET.	35050712
GIMR	2021-04-28	FL	4	RASA1	Loss-of-function mutations; Oncogenic mutations	Non-small cell lung cancer	Trametinib	Preclinical study. RASA1 and NF1 co-mutations define a distinct subset of NSCLC, associated with sensitivity to MEK inhibition, particularly with concurrent loss-of-function mutations.	29127119
GIMR	2023-09-06	FL	4	RB1	Oncogenic mutations	Triple-negative breast cancer	Volasertib; AZD7762		29386107
GIMR	2020-10-26	FL	4	RB1	Oncogenic mutations, Loss-of-function mutations, loss of protein expression	Solid tumours	LY3295668	Preclinical study. Loss-of-function mutations in RB1 gene are common in several treatment-refractory cancers. AURKA inhibitor LY3295668 showed cytotoxic effects in RB1-deficient cancer cells and led to durable regression of RB1(mut) tumor xenografts.	30373917
GIMR	2023-04-12	FL	4	RET	Exon 10 deletion; V591_607del	Medullary thyroid cancer	Pralsetinib	Case report of significance response to Pralsetinib in a MTC patient harbouring two VUS L1016S and in-frame deletion in exon 10.	36053791
GIMR	2025-05-31	FL	4	RET	Fusion	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed  activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2020-04-27	FL	4	RET	Fusions, KIF5B-RET fusion	Non-small cell lung cancer	Cabozantinib	Case report. Best response is SD for 9 months.	30653139
GIMR	2020-04-27	FL	4	RET	Fusions, TRIM33-RET fusion, KIF5B-RET fusion	Non-small cell lung cancer	Cabozantinib	Case series from a Phase 2 study of XL-184 in RET-positive NSCLC. Two responders. DOR not reported.	23533264
GIMR	2020-11-17	FL	4	RET	G810A	Solid tumours	Ponatinib; Lenvatinib		32083997
GIMR	2020-11-17	FL	4	RET	G810S, G810R	Solid tumours	TPX-0046		10.1093/annonc/mdz244.068, 32083997
GIMR	2020-11-17	FL	4	RET	KIF5B-RET fusion, CCDC6-REF fusion, V804M	Solid tumours	Ponatinib	Preclinical study. RET-rearranged tumors. Potent inhibitors AD80 and ponatinib that bind in the DFG-out conformation of RET selectively kill RET-rearranged tumors, while mechanisms of resistance include CCDC6-RET(I788N) mutation and MAPK pathway reactivation.	28615362
GIMR	2020-11-17	FL	4	RET	M918T	Medullary thyroid cancer	Vandetanib	Phase 3 ZETA trial. Post hoc analysis. Vandetanib showed significant improvement in PFS (HR, 0.43) in patients with progressive and symptomatic medullary thyroid cancer, with ORR of 37% versus 2% in placebo arm.	32584630
GIMR	2020-11-17	FL	4	RET	M918T, Oncogenic mutations	Medullary thyroid cancer	Cabozantinib	Exploratory analysis of EXAM trial, but lack of OS benefit even in patients subsequently received an MKI.	27525386, 29045520
GIMR	2020-11-17	FL	4	RET	RET fusions and NOT KIF5B-RET fusion	Non-small cell lung cancer	Agerafenib		31710864
GIMR	2020-11-17	FL	4	RET	V804L, V804M	Solid tumours	Selpercatinib; Pralsetinib	Gatekeeper mutation	32083997
GIMR	2020-11-17	FL	4	RET	V804L, V804M	Thyroid cancer	Ponatinib	Gatekeeper mutation. Thyroid cancer cell lines	23811235
GIMR	2020-06-25	FL	4	RICTOR	Amplification	Gastric cancer	Vistusertib	Preclinical study. RICTOR amplification identified in 2% of 640 patients with metastatic solid tumors, prevalent in 3.8% of gastric cancer, and a RICTOR-amplified patient-derived cell line showed sensitivity to AZD2014-mediated mTORC1/2 inhibition.	28028034
GIMR	2025-06-25	FL	4	RICTOR	Amplification	Non-small cell lung cancer	Sapanisertib	Case report with translational studies. RICTOR amplification occurs in 8-13% of lung cancer cases and is associated with sensitivity to mTORC1/2 inhibitors; an 18-year-old patient with RICTOR-amplified lung cancer achieved tumor stabilization for over 18 months with dual mTORC1/2 inhibitors.	26370156
GIMR	2021-12-06	FL	4	RNF43	Oncogenic mutations	Colorectal adenocarcinoma	RXC004	Phase 1. EudraCT 2017-000720-98. 2 cases of SD in Wnt ligand dependent group (RNF43 mutation or RSPO1 fusion).	10.1016/j.annonc.2021.08.1039
GIMR	2020-07-21	DT	4	RNF43	Oncogenic mutations	Solid tumours	Wnt-C59	Preclinical study. Porcupine inhibitor C59 strongly inhibited growth of Rnf43;Znrf3-mutant intestinal neoplasia by suppressing paracrine Wnt-driven growth, while sparing adjacent normal crypts.	26023187
GIMR	2021-07-21	FL/DT	4	RNF43	Truncating mutations, Frameshift mutations, C-terminal truncating mutations, Loss-of-function mutations, Oncogenic mutations, Deletion, R371fs, G659fs, P660fs	Pancreatic adenocarcinoma	ETC-159	RNF43 truncating and frameshift mutations, and  are sensitive to PORCN inhibitors in cell line assay.	33067269
GIMR	2021-01-20	FL	4	ROS1	Amplification	Solid tumours	Entrectinib; Brigatinib; Repotrectinib	STARTRK-1 reported only 1 case of amplification. ROS1 amplification included as inclusion criteria for NCT02097810, NCT03868423, NCT04094610.	28183697, NCT02097810, NCT03868423, NCT04094610
GIMR	2024-07-03	FL	4	ROS1	CD74-ROS1 fusion, L2026M	Non-small cell lung cancer	APG-2449	Preclinical study. APG-2449 is a ALK/ROS1/FAK inhibitor	35820889
GIMR	2021-12-12	FL	4	ROS1	EZR-ROS1 fusion	Non-small cell lung cancer	Crizotinib	Case report. Crizotinib resulted in a 6-month clinical benefit in a NSCLC patient harbouring EZR-ROS1 fusion. 	29361925
GIMR	2021-12-12	FL	4	ROS1	EZR-ROS1 fusion	Papillary thyroid cancer	Entrectinib		32913977
GIMR	2025-05-31	FL	4	ROS1	Fusion	Non-small cell lung cancer	Izalontamab brengitecan	Phase Ib study. N=68. iza-bren, an EGFR x HER3 bispecific ADC, showed  activity in NSCLC patients with driver mutations outside of classic ALK/ROS1/RET fusions, with ORR of 35% and mPFS of 4.5 months.	10.1200/JCO.2025.43.16_suppl.3001
GIMR	2022-01-21	FL	4	ROS1	Fusion, CD74-ROS1 fusion, G2032R	Non-small cell lung cancer	Repotrectinib	In both cell line and xenograft models, repotrectinib was active against preclinical models harbouring CD74-ROS1 fusion with or without G2032R subsitution. 	32269053
GIMR	2022-01-21	FL	4	ROS1	Fusion, G2032R, D2033N	Solid tumours	Repotrectinib	Cell line study. Repotrectinib was shown to be active in acquired solvent-front substitutions with ALK, ROS1, NTRK1-3 oncogenic fusions in cell line models.	30093503
GIMR	2021-04-03	FL	4	ROS1	Fusion; GOPC-ROS1 Fusion	Ovarian cancer	Crizotinib	Case report of high-grade serous ovarian cancer	32652753
GIMR	2020-04-25	FL	4	ROS1	Fusions	Non-small cell lung cancer	AZD3463		26372962
GIMR	2020-04-25	FL	4	ROS1	Fusions	Non-small cell lung cancer	Brigatinib	Not TGA approved	10.1200/PO.18.00267, 10.1158/1538-7445.AM2013-5655
GIMR	2020-06-16	FL	4	ROS1	Fusions	Non-small cell lung cancer	Cabozantinib	Case report. Cabozantinib showed effectiveness in treating a CD74-ROS1-positive advanced NSCLC patient for 1.5 years, and subsequent crizotinib therapy remained effective after cabozantinib resistance developed.	32103985
GIMR	2020-04-16	FL	4	ROS1	Fusions	Solid tumours	ROS1 inhibitor		32760015
GIMR	2020-04-25	FL	4	ROS1	Fusions; G2032R	Non-small cell lung cancer	Taletrectinib	Preclinical study. DS-6051b, a selective ROS1/NTRK inhibitor, showed growth inhibition in ROS1-rearranged cancers with crizotinib-resistant G2032R mutation, overcoming resistance to crizotinib, lorlatinib, and entrectinib.	31399568
GIMR	2020-04-25	FL	4	ROS1	G2032R	Non-small cell lung cancer	Cabozantinib	Preclinical study and case report highlighting ROS1-rearranged NSCLC with secondary resistance mutation, where cabozantinib overcomes crizotinib resistance by effectively inhibiting ROS1 wild-type and resistant mutants, including G2032R mutation.	31395437, 25351743
GIMR	2023-04-14	FL	4	ROS1	G2032R	Solid tumour	Taletrectinib; Repotrectinib; NVL-520	Preclinical study. NVL-520 is a selective and brain-penetrant inhibitor of ROS1 fusions and secondary resistance mutations, showing potent targeting of ROS1 and diverse ROS1 resistance mutations with high selectivity for ROS1 G2032R over TRK.	36511802
GIMR	2021-07-09	FL	4	ROS1	SLC12A2-ROS1 fusion	Non-small cell lung cancer	Crizotinib	Case report. Novel SLC12A2-ROS1 fusion identified in NSCLC patient, who showed significant response to crizotinib, highlighting the importance of choosing the appropriate next-generation sequencing assay.	33682977
GIMR	2023-04-14	FL	4	ROS1	SLC34A2-ROS1 fusion, EZR-ROS1 fusion, CD74-ROS1 fusion, GOPC-ROS1 fusion, CEP85L-ROS1 fusion	Solid tumour	Crizotinib; Entrectinib; Loratinib; Taletrectinib; Repotrectinib; NVL-520	Preclinical study. NVL-520 showed potent targeting of ROS1 and diverse ROS1 resistance mutations with high selectivity for ROS1 G2032R over TRK and brain penetration.	36511802
GIMR	2021-01-31	FL	4	ROS1	SLC4A4-ROS1 fusion	Pancreatic adenocarcinoma	Entrectinib	Case series. KRAS wild-type PDAC. Stable disease with duration of treatment of 7 months.	10.1200/PO.18.00039
GIMR	2021-12-06	FL	4	RSPO1	Fusion	Colorectal adenocarcinoma	RXC004	Phase 1. EudraCT 2017-000720-98. 2 cases of SD in Wnt ligand dependent group (RNF43 mutation or RSPO1 fusion).	10.1016/j.annonc.2021.08.1039
GIMR	2023-06-14	FL	4	SETD2	Oncogenic mutations	Ovarian cancer	Camonsertib	Phase 1. TRESR. Responses are seen in solid tumours with BRCA1/2, RAD51C, SETD2, ATM, CDK12 mutations.	37277454
GIMR	2024-06-02	FL	4	SEZ6	Protein expression	Small-cell lung cancer; Neuroendocrine carcinoma; Solid tumour	ABBV-706	Phase 1, first-in-human study of ABBV-706. N=49. ORR was 21% (7 PRs), with 40% in SCLC and 6% in neoruendocrine neoplasms. CBR was 91%. SEZ6 expression is not required for enrollment.	10.1200/JCO.2024.42.16_suppl.3001
GIMR	2024-04-04	FL	4	SF3B1	H662Q, K700E, R625H, R625C, R625L	Pancreatic adenocarcinoma	Talazoparib; Talazoparib + AZD0156	Preclinical study. Synthetic lethal drug screens revealed that SF3B1 mutant cell lines are selectively sensitive to PARP inhibition in cell line models as well as antitumor effects in in vivo models.	37524790
GIMR	2022-02-02	FL	4	SF3B1	Oncogenic mutations	Myelodysplastic syndrome; Chronic myelomonocytic leukaemia; Acute myeloid leukaemia	H3B-8800	Phase 1. N=27. No CR or PR meeting IWG criteria but nine RBC transfusion free intervals were observed, including 5 of 15 transfusion-dependent MDS cases.	34172893
GIMR	2022-02-02	FL	4	SF3B1	Oncogenic mutations	Solid tumours; Liquid cancers	H3B-8800	Preclinical study. H3B-8800, an orally available splicing modulator, preferentially kills spliceosome-mutant cancer cells bearing mutations in SF3B1, U2AF1, and SRSF2 by retaining short, GC-rich introns, with loss of activity observed in drug-resistant cells with mutations in SF3b components.	29457796
GIMR	2020-06-26	FL	4	SLC1A5	Overexpression	Liquid cancers	MEDI7247		10.1200/JCO.2018.36.15_suppl.TPS2603
GIMR	2020-09-03	FL	4	SLC1A5	Overexpression	Solid tumours	MEDI7247		10.1158/1538-7445.AM2018-LB-298
GIMR	2025-06-09	FL	4	SLC39A6	Protein expression	Solid tumours	BRY812	Phase 1 trial. NCT06038058. N=36. BRY812, an ADC targeting LIV-1, demonstrated an ORR of 24% (8/34) in breast cancer, with response rates increasing to 43% (6/14) in patients with high LIV-1 expression (PS2+).	10.1200/JCO.2025.43.16_suppl.3021
GIMR	2021-01-18	FL	4	SLX4	Loss-of-function mutations	Solid tumours	Olaparib	Cell line study showing differential sensitivity to olaparib in SLX4 mutants (vs. wild type).	27084631
GIMR	2020-06-15	FL	4	SMARCA2	Loss-of-function mutations	Ovarian small cell carcinoma	Tazemetostat	Preclinical study. Xenograft and cell line SCCOHT models deficient in SMARCA2 and SMARCA4 showed antiproliferative and antitumour effects when treated with EZH2 inhibitor tazemetostat, exemplifying an additional class of rhabdoid-like tumours dependent on EZH2 activity for survival.	28292935
GIMR	2021-12-15	FL	4	SMARCA2+SMARCA4	SMARCA2:Loss of protein expression and SMARCA4:Loss of protein expression	Ovarian small cell carcinoma	Tazemetostat	Cell lines and xenograft study. Inhibition of EZH2 by Tazemetostat selectively kills small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cells deficient in SMARCA2 and SMARCA4.	28292935
GIMR	2022-06-08	FL	4	SMARCA4	Loss of protein expression	Malignant rhabdoid tumor	Pembrolizumab	Case report. Response seen in thoracic MRT with prolonged clinical benefit and durable response (11+ months). Concomitant SMARCA2 loss of expression was also identified.	31114851
GIMR	2021-12-15	FL	4	SMARCA4	Loss of protein expression	Ovarian small cell carcinoma	Tazemetostat	Preclinical study. Tazemetostat, an EZH2 inhibitor, showed antiproliferative and antitumor effects in SMARCA2- and SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cell lines and xenografts, indicating EZH2 dependence in this subset of tumors with SWI/SNF mutations.	28292935
GIMR	2021-04-14	FL	4	SMARCA4	Loss-of-function mutations	Non-small cell lung cancer	Palbociclib	Preclinical study. SMARCA4 loss is synthetic lethal with CDK4/6 inhibition in NSCLC, due to reduced cyclin D1 expression caused by restricted CCND1 chromatin accessibility and suppressed c-Jun, a transcription activator of CCND1.	30718506
GIMR	2021-04-14	FL	4	SMARCA4	Loss-of-function mutations	Ovarian small cell carcinoma	Palbociclib	Preclinical study. SMARCA4-deficient small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) cells with downregulated cyclin D1 are sensitive to CDK4/6 inhibitors, suggesting a potential therapeutic application for CDK4/6 inhibitors in SCCOHT with SMARCA4 inactivating mutations.	30718512
GIMR	2020-06-15	FL	4	SMARCA4	Loss-of-function mutations	Ovarian small cell carcinoma	Tazemetostat	Xenograft and cell line SCCOHT models. Induces potent antiproliferative and antitumour effects.	24563539
GIMR	2021-01-13	FL	4	SMARCA4	Loss-of-function mutations	Ovarian small cell carcinoma	Tazemetostat	Single case report of SCCOHT. Concurrent loss of SMARCA2 expression. Partial response after four months with clinical benefit of eight months seen in chemo-resistant disease.	32575483
GIMR	2025-08-31	FL	4	SMARCA4	Loss-of-function mutations	Ovarian small cell carcinoma	Tazemetostat	Case report. 32-year-old patient with small-cell carcinoma of ovary hypercalcemic type (SCCOHT) treated with off-label tazemetostat (EZH2 inhibitor) achieved durable response but developed secondary T-cell acute lymphoblastic lymphoma (T-ALL), suggesting dual role of epigenetic therapy in tumor suppression and potential oncogenesis.	39167815
GIMR	2025-08-17	FL	4	SMARCA4	Oncogenic mutations	Ovarian small cell carcinoma	GSK126; Tazemetostat	Preclinical study. SCCOHT tumor samples (N=24). 80% (19/24) showed strong EZH2 expression; re-expression of SMARCA4 suppressed EZH2. SCCOHT cells hypersensitive to EZH2 inhibitors (GSK126, EPZ-6438), inducing cell cycle arrest, apoptosis, differentiation, and improved survival in xenograft models.	28444909
GIMR	2022-02-09	FL	4	SMARCA4	Oncogenic mutations	Pancreatic adenocarcinoma	Pembrolizumab; Durvalumab; Atezolizumab; Nivolumab	Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status.	34375311
GIMR	2023-01-11	FL	4	SMARCA4	Oncogenic mutations	SMARCA4-deficient thoracic sarcoma	Pembrolizumab	Case report. Exceptional response to pembrolizumab observed in a SMARCA4-deficient thoracic sarcoma overexpressing PD-L1, suggesting pembrolizumab as a potential treatment strategy for PD-L1-positive SMARCA4-DTS.	31617320
GIMR	2024-08-29	FL	4	SMARCA4	Oncogenic mutations	Solid tumours	A947	Preclinical study. Synthetic lethality and cell growth inhibition were observed in SMARCA4 mutant cancer through selective SMARCA2 degradation in in vitro models.	36357397
POTTR	2020-04-16	FL	4	SMARCA4	Oncogenic mutations	Solid tumours	BET inhibitor	Preclinical study. Bromodomains are acetyl lysine 'reader' modules with potential anticancer activities, and BET inhibitor programmes provide insights for developing non-BET bromodomain-targeting drugs.	31273347
GIMR	2024-08-29	FL	4	SMARCA4	Oncogenic mutations	Solid tumours	PRT3789	Phase 1. NCT05639751. PRT3789 selectively targets SMARCA4-deficient cells with anti-tumor activity and synergistic effects with therapies.	10.1158/1535-7163.TARG-23-B113
GIMR	2024-09-14	FL	4	SMARCA4	Oncogenic mutations	Solid tumours	PRT3789	Phase 1. NCT05639751. Across dose levels, responses were see in PRT3789 including 3 partial responses and prolonged stable disease in patients with advanced solid tumors with SMARCA4 mutations. 	10.1016/j.annonc.2024.08.670
GIMR	2024-09-02	FL	4	SMARCA4	Oncogenic mutations	Solid tumours	PRT7732	Preclinical study. PRT7732 induces synthetic lethality in SMARCA4-deficient cancers with low nanomolar DC50 values and significant tumor growth inhibition in xenograft models.	10.1158/1538-7445.AM2024-4503
GIMR	2022-02-09	FL	4	SMARCB1	Oncogenic mutations	Pancreatic adenocarcinoma	Pembrolizumab; Durvalumab; Atezolizumab; Nivolumab	Retrospective case series. In PDAC harbouring alterations in the SWI/SNF complex, 8 of 9 patients had response to ICI (including 1 CR) irrespective to MSI, low TMB, PD-L1 expression status, with median PFS and OS of 9 and 15 months, respectively, and 2 patients having ongoing responses at 33+ and 36+ months.	34375311
GIMR	2020-06-15	FL	4	SMARCB1	Oncogenic mutations	Rhabdoid tumors	Tazemetostat	Phase 1. NCT02900664. In children with genetically altered malignant rhabdoid tumors (MRTs) or atypical teratoid rhabdoid tumors (ATRTs), inhibition of EZH2 with a small-molecule inhibitor led to durable tumor regression. The inhibitor induced apoptosis and differentiation specifically in SMARCB1-deleted MRT cells. Treatment in xenograft-bearing mice resulted in dose-dependent regression of MRTs and prevention of tumor regrowth after dosing cessation.	23620515
GIMR	2025-04-25	FL	4	SMARCB1	Oncogenic mutations	Solid tumours	FHD-609	Phase 1. NCT04965753. N=55. FHD-609 demonstrated dose-dependent pharmacokinetic exposure, with a maximum tolerated dose of 40 mg twice weekly or 80 mg once weekly. Preliminary clinical activity included one partial response and eight cases of stable disease.	39660994
GIMR	2021-07-04	FL	4	SMC3	Oncogenic mutations	Myelodysplastic syndrome; Acute myeloid leukaemia	Talazoparib	Cell line study. Inactivation of SMC3 or RAD21, and STAG2 mutations, increase sensitivity to PARP inhibition.	33351783
GIMR	2022-03-04	FL	4	SMO	D477G, E522K, G457S, S391N, D388N, N223D, L225R	Basal cell carcinoma; Medulloblastoma	Itraconazole; Arsenic trioxide	Preclinical study. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation, showing activity against tumors with acquired resistance to Smoothened antagonists, including SMO(D477G) mutant.	23291299
SuboKB	2020-04-16	ST	4	SMO	Oncogenic mutations	Basal cell carcinoma	Posaconazole	Preclinical study. Posaconazole inhibits Hedgehog signaling pathway by antagonizing Smoothened (SMO) with a distinct mechanism, showing robust activity against drug-resistant SMO mutants and inhibiting Hh-dependent basal cell carcinoma growth in vivo.	26823493
GIMR	2020-04-16	ST	4	SMO	Oncogenic mutations	Solid tumours	JQ1	Preclinical study. BET bromodomain inhibition through JQ1 effectively targets Hedgehog-driven tumors, including those with genetic lesions conferring resistance to Smoothened antagonists, by directly regulating GLI transcription.	24973920
SuboKB	2020-04-16	ST	4	SMO	Oncogenic mutations	Solid tumours	Taladegib		10.1158/1078-0432.CCR-17-0723
GIMR	2023-04-11	FLHS	4	SRSF2	P95H	Acute myeloid leukaemia	Olaparib	Cell line study. Mutation in spliceosomes causes accumulation of R-loops in cells, triggering a PARP1 response. PARP inhibition with Olaparib has shown to prolong survival in murine model of myeloid leukaemia harbouring SRSF2 P95H mutation.	10.1158/1538-7445.AM2023-6183
GIMR	2022-02-02	FL	4	SRSF2	P95H	Chronic myelomonocytic leukaemia	H3B-8800		29457796
GIMR	2025-03-02	FL	4	SRSF2	P95H, Oncogenic mutations	Myelodysplastic syndrome	Talazoparib	Preclinical study. Pathogenic SRSF2 activating mutations elevate protein poly-ADP-ribosylation levels, making mutant cells more vulnerable to PARP inhibitors in Srsf2 P95H knock-in murine hematopoietic cell and MLL-AF9 leukemia models.	38806724
GIMR	2025-04-25	FL	4	SS18	SS18-SSX fusion	Synovial sarcoma	BI-7273	Preclinical study. BRD9 inhibition selectively targets and degrades the protein in synovial sarcoma, reversing oncogenic gene expression and demonstrating potent anti-tumor activity.	39660994
GIMR	2025-04-25	FL	4	SS18	SS18-SSX fusion	Synovial sarcoma	FHD-609	Phase 1. NCT04965753. N=55. FHD-609 demonstrated dose-dependent pharmacokinetic exposure, with a maximum tolerated dose of 40 mg twice weekly or 80 mg once weekly. Preliminary clinical activity included one partial response and eight cases of stable disease.	39660994
GIMR	2025-05-31	FL	4	SSTR2	Protein expression	Neuroendocrine tumour	212Pb-VMT-alpha-NET	Phase 1/2a study. NCT05636618. [212Pb]VMT-α-NET. 3/7 patients achieving partial responses at 185 MBq dose level in SSTR2-expressing neuroendocrine tumors. DOTATATE-positive	10.1200/JCO.2025.43.16_suppl.3005
GIMR	2021-07-04	FL	4	STAG2	Oncogenic mutations	Myelodysplastic syndrome; Acute myeloid leukaemia	Talazoparib	Cell line study. STAG2-mutant cells have increased DNA damage and are sensitive to PARP inhibition, suggesting that targeting DNA damage repair pathways may be a potential therapeutic strategy for cohesin-mutant malignancies including MDS/AML.	33351783
GIMR	2025-06-09	FL	4	STEAP1	Protein expression	Prostate cancer	Xaluritamig	Phase 1 study. Xaluritamig, a STEAP1-targeted T-cell engager, showed responses (49% PSA50; 24% ORR) in patients with metastatic castration-resistant prostate cancer, with greater frequency at target doses ≥0.75 mg (59% PSA50; 41% ORR). Note relationship between STEAP1 expression and response was not prospectively assessed in this study.	37861461
GIMR	2021-10-22	FL	4	STK11	Oncogenic mutations	Non-small cell lung cancer	Alrizomadlin + Pembrolizumab	Phase 2 trial (ongoing). NCT03611868. STK11-mutated lung adenocarcinoma N=5. ORR 0% and DCR 25%.	10.1200/JCO.2021.39.15_suppl.2506
GIMR	2024-08-21	FL	4	STK11	Oncogenic mutations	Non-small cell lung cancer	Everolimus		34422335
SuboKB	2020-04-16	ST	4	STK11	Oncogenic mutations	Pancreatic adenocarcinoma	Everolimus	Case reports	21189378
SuboKB	2020-04-16	ST	4	STK11	Oncogenic mutations	Pituitary adenoma	Everolimus	Case reports	27615706
GIMR	2020-11-26	FL	4	SUZ12	Loss-of-function mutations	Solid tumours	JQ1	PRC2 loss sensitizes cancers to bromodomain inhibitors	25119042
GIMR	2025-06-09	FL	4	TACSTD2	Protein expression	Solid tumours	BAT8008	Phase 1 study. NCT05620017. N=170. BAT8008 showed activity in advanced cervical cancer (ORR 36%, PFS 6.8 months) and oesophageal cancer (ORR 23%, PFS 5.3 months).	10.1200/JCO.2025.43.16_suppl.3024
GIMR	2020-05-01	FL	4	TACSTD2	Protein expression	Triple-negative breast cancer	Sacituzumab Govitecan	PFS Trop-2 staining higher in expressors	28291390
GIMR	2022-12-21	FL	4	TACSTD2	Protein expression, Overexpression	Solid tumours	Datopotamab Deruxtecan		34413126
GIMR	2025-06-23	FL	4	TACSTD2	Protein expression, Overexpression	Triple-negative breast cancer	Sacituzumab Govitecan	Phase 2 TROPiCS-03 basket trial. NCT03964727. N = 43. Objective response rate was 16% and clinical benefit rate was 28% in heavily pretreated advanced HNSCC patients receiving Sacituzumab Govitecan, with median duration of response, PFS, and OS being 4.2, 4.1, and 9.0 months. Note Trop 2 expression was assesed as an exploratory endpoint. Patients were enroleld prospectively as Trop2 expression is  highly expressed in HNSCC.	39665770
GIMR	2023-07-11	FL	4	TP53	Oncogenic mutation	Chronic lymphocytic leukaemia	Ceralasertib	Cell line and xenograft study. AZD6738 induce cell death in CLL cell lines and primary cells  with TP53 or ATM defects, where inhibition of ATR signaling led to the accumulation of unrepaired DNA damage and cell death by mitotic catastrophe in TP53- or ATM-defective CLL cells. AZD6738 sensitized TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. 	26563132
GIMR	2023-07-11	FL	4	TP53	Oncogenic mutation	Chronic lymphocytic leukaemia	Ceralasertib + Chlorambucil; Ceralasertib + Fludarabine; Ceralasertib + Bendamustine; Ceralasertib + Ibrutinib	Cell line and xenograft study. AZD6738 sensitises TP53- or ATM-defective CLL cells to chemotherapy and ibrutinib. 	26563132
GIMR	2023-07-11	FL	4	TP53	Oncogenic mutation	Solid tumour	VE-821 + Cisplatin; VE-821	Cell line study. ATR inhibition Is synthetic lethal with the ATM-p53 tumor pathway when cells are exposed to DNA-damaging agents.	21490603
GIMR	2025-02-24	FL	4	TP53	Oncogenic mutation	Solid tumours	Tuvusertib	Preclinical study. NCT04170153. N=55. Molecular responses were associated with mutations in TP53. Complete molecular responses were observed in ARID1A, ATRX, DAXX, and BRCA1/2.	38407317
GIMR	2024-05-14	FL	4	TP53	Oncogenic mutations	Colorectal adenocarcinoma; Pancreatic adenocarcinoma	TAS-102 + Olaparib; TAS-102 + Talazoparib	Cell line study. In vitro study showed that trifluorothymidine and PARP inhibitor demonstrated synergistic activity against p53-mutant colorectal and pancreatic cancers with higher anti-neoplastic activity in p53-mutant models.	38387463
GIMR	2021-06-07	FL	4	TP53	Oncogenic mutations	Solid tumours	AMG-650	Cell line study. Targeting KIF18A in has shown mitotic arrest in MDA-MB-157 cell lines. Ongoing phase 1 trial NCT04293094.	35286090, 10.1200/JCO.2021.39.15_suppl.TPS5600
GIMR	2022-06-04	FL	4	TP53	Oncogenic mutations	Solid tumours	LY3143921	Phase 1. NCT03096054.	10.1200/JCO.2022.40.16_suppl.3103
GIMR	2022-06-04	FL	4	TP53	Overexpression, P151S, Y163C, R175H, L194R, Y220C, R248Q, R248W, R273C, R273H, R273L, R282W	Endometrial cancer; Uterine serous carcinoma	Carboplatin + Paclitaxel + Bevacizumab	Exploratory analysis of GOG-86P. NCT00977574. p53 IHC and/or TP53 gain-of-function mutations determines a subgroup of patient where addition of bevacizumab to chemotherapy in both PFS and OS. Overexpression was defined >= 80% of tumor cell nuclei showing intense staining by IHC.	35658479
GIMR	2022-01-05	FL	4	TP53	Y220C	Solid tumours	PC14586	PYNNACLE trial. NCT04585750. ORR was 8/31 (32%) in the 1150mg BD cohort across tumour types.	10.1158/1538-7445.AM2021-LB006, 10.1200/JCO.2022.40.16_suppl.3003
GIMR	2023-09-15	FL	4	TP53+RB1	TP53:Oncogenic mutations AND RB1:Oncogenic mutations, TP53:Oncogenic mutations AND RB1:Deletion	Prostate cancer	Talazoparib + VX-970	Cell line study. Prostate cancers with TP53 and RB1 loss may be associated with poor outcomes, stem-like properties, and may exhibit loss of AR activity. TP53/RB1 mutants are sensitive to PARP and ATR inhibition in cell-line models.	32460015
GIMR	2023-07-14	FL	4	TP63	Amplification	Lung squamous cell carcinoma	HMBD-001		10.1158/1538-7445.AM2023-2659
GIMR	2022-03-20	FL	4	TSC1	Oncogenic mutations	Perivascular epithelioid cell tumour	Everolimus	Phase 3 EXIST-2 trial. NCT00790400. Everolimus showed significant angiomyolipoma response rate of 42% (50% reduction in total volume) compared to 0% with placebo in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.	23312829
GIMR	2020-04-27	FL	4	TSC1	Oncogenic mutations	Renal cell carcinoma	Everolimus	Mutations in MTOR, TSC1, or TSC2 were more common in responders (28%) than nonresponders (11%) to rapalogs in metastatic renal cell carcinoma, indicating a potential association between mTOR pathway gene mutations and treatment response.	26831717
GIMR	2020-06-11	FL	4	TSC1	Oncogenic mutations	Renal cell carcinoma	Everolimus	No survival benefit vs Sunitinib	29390043
GIMR	2021-06-08	FL	4	TSC1	Oncogenic mutations	Solid tumours	Nab-sirolimus	Case series.	10.1200/JCO.2021.39.15_suppl.3111
GIMR	2021-09-29	FL	4	TSC2	Loss-of-function mutations, Q1178*	Anaplastic thyroid cancer 	Everolimus	Case report. Exceptional responder to everolimus for 18 months.	25295501
GIMR	2022-03-20	FL	4	TSC2	Oncogenic mutations	Perivascular epithelioid cell tumour	Everolimus	Phase 3 EXIST-2 trial. NCT00790400. Everolimus showed significant angiomyolipoma response rate of 42% (50% reduction in total volume) compared to 0% with placebo in patients with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis.	23312829
GIMR	2022-03-20	FL	4	TSC2	Oncogenic mutations	Perivascular epithelioid cell tumour	Sirolimus; Temsirolimus; Everolimus	Case series. Showing activity of mTOR inhibitors in extrarenal PEComas with TSC1/2 mutation or LOH.	22927055, 20048174, 20215136
GIMR	2020-04-27	FL	4	TSC2	Oncogenic mutations	Renal cell carcinoma	Everolimus	Drug is PBS reimbursed, but not biomarker selected	26831717
GIMR	2020-06-11	FL	4	TSC2	Oncogenic mutations	Renal cell carcinoma	Everolimus	Phase 2 RECORD-3 study. NCT00903175. No significant difference in OS between first-line everolimus followed by sunitinib and first-line sunitinib followed by everolimus in metastatic RCC.	29390043
GIMR	2021-06-08	FL	4	TSC2	Oncogenic mutations	Solid tumours	Nab-sirolimus	Case series.	10.1200/JCO.2021.39.15_suppl.3111
GIMR	2021-06-15	FL	4	Tumour microenvironment	Inflamed immune phenotype	Triple-negative breast cancer	Atezolizumab + Nab-paclitaxel	Retrospective analysis from IMpassion130. Inflammed immune phenotype showed both improved PFS and OS in PD-L1 IC-positive subgroup.	10.1200/JCO.2021.39.15_suppl.1006
GIMR	2024-06-18	FL	4	Tumour Mutational Burden	High	Breast cancer; Hepatobiliary cancers; Solid Tumours	Atezolizumab	Phase 2. TAPISTRY trial. NCT04589845. N=150. Atezolizumab showed ORR of 23% (TMB ≥16 mut/Mb) and 20% (TMB ≥13 mut/Mb), with median PFS of 2.8 months and 2.7 months, respectively, in patients with TMB-high solid tumors. TMB was assessed by Foundation One CDx. Tumour types with n>=4 are identifed; no objective responses were seen in breast and hepatobiliary cancers.	10.1200/JCO.2024.42.17_suppl.LBA2509
GIMR	2020-09-25	FL	4	Tumour Mutational Burden	High	Colorectal adenocarcinoma	Pembrolizumab	Phase 2 KEYNOTE-158 study. NCT02628067. Prospective biomarker analysis in 790 patients showed tTMB-high status (>=10 mutations per megabase) was associated with improved ORR to pembrolizumab (29% vs 6% in non-tTMB-high). However, tTMB could be a novel predictive biomarker for response to pembrolizumab in patients with advanced solid tumours, KEYNOTE-158 did not include MSS colorectal cancers.	32919526
GIMR	2020-11-13	FL	4	Tumour Mutational Burden	High	Gastric cancer	Toripalimab	Phase Ib/2 NCT02915432 trial. Toripalimab demonstrated an overall response rate of 12.1% and median overall survival of 4.8 months in chemo-refractory gastric cancer. The TMB-high group exhibited significantly superior overall survival of 14.6 months compared to 4.0 months, with an objective response rate of 33% versus 6% in the low TMB group at the 12 mutations/MB threshold.	31236579
GIMR	2020-11-26	FL	4	Tumour Mutational Burden	High	Non-small cell lung cancer	Nivolumab	Exploratory analysis from Checkmate 026. High TMB was defined as highest third of mutations in the study cohort.	28636851
GIMR	2020-06-08	FL	4	Tumour Mutational Burden	High	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody; immune checkpoint blockade,PD-1 targeting; immune checkpoint blockade,PD-L1 targeting	Pan-cancer analysis of 1,662 patients treated with immune checkpoint inhibitors (ICI) showed higher tumor mutational burden (TMB) associated with improved overall survival across multiple cancer types, although TMB cutpoints varied between cancer types.	30643254
GIMR	2020-11-11	FL	4	Tumour Mutational Burden	High	Solid tumours	Tremelimumab		ACTRN12620000918921
GIMR	2020-04-16	FL	4	Tumour Mutational Burden	High	Solid tumours except Colorectal adenocarcinoma	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	MSS with High TMB Benefit from IO: However this is a retrospective, hypothesis seeking study.	31405947
GIMR	2025-06-29	FL	4	Tumour Mutational Burden	High	Urothelial carcinoma	Pembrolizumab + Cisplatin + Gemcitabine; Pembrolizumab + Carboplatin + Gemcitabine	Phase 3 KEYNOTE-361 trial. NCT02853305. N=993. Primary endpoints of PFS (HR 0.78, P=0.0033) and OS (HR 0.86, P=0.0407) were not met for pembrolizumab plus chemotherapy versus chemotherapy. TMB as a continuous variable was significantly associated with improved ORR, PFS, and OS in pembrolizumab monotherapy (one-sided P<0.001, P<0.001, P=0.007), with highest benefits observed in patients with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 versus chemotherapy alone. Cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1) were prespecified.	39475359
GIMR	2021-10-12	FL	4	Tumour Mutational Burden+Microsatellite	Tumour Mutational Burden:High and Microsatellite:Stable	Colorectal adenocarcinoma	Durvalumab + Tremelimumab	Randomized phase 2 study. CCTG CO.26. Durvalumab and tremelimumab combination was associated with an improved OS over best supportive care (6.6 vs 4.1 months). TMB cut off was determined to be 28 mutations per MB (post hoc). POLE status was not determined.	32379280
GIMR	2021-10-12	FL	4	Tumour Mutational Burden+Mismatch repair	Tumour Mutational Burden:High and Mismatch repair:Proficient	Colorectal adenocarcinoma	Durvalumab + Tremelimumab	Randomized phase 2 study. CCTG CO.26. Durvalumab and tremelimumab combination was associated with an improved OS over best supportive care (6.6 vs 4.1 months). TMB cut off was determined to be 28 mutations per MB (post hoc). POLE status was not determined.	32379280
GIMR	2023-04-11	FLHS	4	U2AF1	S34F	Acute myeloid leukaemia	Olaparib	Cell line study. Mutation in spliceosomes causes accumulation of R-loops in cells, triggering a PARP1 response. PARP inhibition with Olaparib has shown to prolong survival in murine model of myeloid leukaemia harbouring SRSF2 P95H mutation.	10.1158/1538-7445.AM2023-6183
GIMR	2026-03-04	FL	4	VEGFA	High gene expression	Biliary tract cancer	Atezolizumab + Bevacizumab + Cisplatin + Gemcitabine	Phase 2. IMbrave151. NCT04677504. N=162. BTCs respond poorly to PD-1/PD-L1 inhibitors. Atezolizumab (anti-PD-L1) plus bevacizumab plus cisplatin and gemcitabine versus atezolizumab plus placebo plus cisplatin and gemcitabine in untreated advanced BTC. Median PFS 8.3 months versus 7.9 months (HR, 0.67). Median OS 14.9 versus 14.6 months (HR, 0.97). High VEGFA gene expression associated with improved PFS (HR, 0.44).	39423355
GIMR	2022-01-19	FL	4	VHL	Oncogenic mutations	Renal cell carcinoma	Belzutifan	Phase 1. NCT02974738. The dose expansion cohort of this single-arm study with Belzutifan showed an ORR of 25% (14/55). DCR was 80% (44/55). Note VHL mutational status was not reported in this study, although VHL loss is common in RCC. 	33888901
GIMR	2025-06-21	FL	4	WT1	EWSR1-WT1 fusion	Desmoplastic small round cell tumours	Palbociclib	Preclinical study. Comprehensive transcriptomic analysis reveals CDK4/6 inhibitors as potential therapeutic agents for Desmoplastic Small Round Cell Tumors by targeting the cyclin D-CDK4/6-RB axis upregulated by EWSR1-WT1, with palbociclib demonstrating reduced tumor growth in xenograft models.	38588409
GIMR	2021-06-09	FL	4	XRCC2	Loss-of-function mutations	Breast cancer	Olaparib	Preclinical study. Synthetic lethal screening in MCF7 cells identified sensitivity to PARG inhibitor PDD00017273 in DNA damage-response deficient cells with BRCA1, BRCA2, PALB2, FAM175A, and BARD1 deficiencies, suggesting potential for single treatment therapy in HR deficient tumours.	28254358
GIMR	2020-05-21	FL	R1	ABL1	T315I	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Bosutinib; Imatinib; Nilotinib	Acquired resistance	22371878, 14676625
GIMR	2020-05-21	FL	R1	ABL1	T315I	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Dasatinib	Acquired resistance	16775234
GIMR	2020-05-21	FL	R1	ABL1	V299L	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Bosutinib	Acquired resistance	19075254
GIMR	2020-05-21	FL	R1	ABL1	V299L, T315A, F317L, F317V, F317I, F317C	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Dasatinib	Acquired resistance	19075254, 25379619
GIMR	2020-05-21	FL	R1	ABL1	Y253H, E255K, E255V, F359V, F359C, F359I	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Nilotinib	Acquired resistance	19075254, 25379619
GIMR	2020-05-21	FL	R1	ABL1	Y253H, E255K, E255V, T315A, F317L, F317V, F317I, F317C, F359C, F359I, F359V, F486S	Acute lymphoblastic leukaemia; Chronic myelogenous leukaemia	Imatinib	Acquired resistance	19075254
GIMR	2020-05-04	FL	R1	BRAF	V600E	Colorectal adenocarcinoma	Panitumumab; Cetuximab; Cetuximab + Irinotecan; Cetuximab + FOLFIRI; FOLFOX + Panitumumab	Not explicitly excluded by TGA but not recommended by NCCN and ESMO 2016 consensus guidelines.	20619739
GIMR	2020-04-16	FL	R1	EGFR	Exon 20 insertion except A763_Y764insFQEA	Non-small cell lung cancer	Gefitinib; Neratinib; Afatinib; Erlotinib; Dacomitinib		21764376
GIMR	2020-04-16	FL	R1	EGFR	T790M	Non-small cell lung cancer	Gefitinib; Neratinib; Afatinib; Erlotinib; Dacomitinib		18227510
GIMR	2020-04-16	FL	R1	KRAS	Oncogenic mutations	Colorectal adenocarcinoma	Panitumumab; Cetuximab; Cetuximab + Irinotecan; Cetuximab + FOLFIRI; FOLFOX + Panitumumab	RAS mutations, including KRAS and NRAS, were associated with resistance to anti-EGFR therapy, with patients having RAS wild-type tumors showing improved PFS and OS when treated with panitumumab-FOLFOX4 or cetuximab.	24024839, 18946061
GIMR	2020-04-16	FL	R1	NRAS	Oncogenic mutations	Colorectal adenocarcinoma	Panitumumab; Cetuximab; Cetuximab + Irinotecan; Cetuximab + FOLFIRI; FOLFOX + Panitumumab	RAS mutations, including KRAS and NRAS, were associated with resistance to anti-EGFR therapy, with patients having RAS wild-type tumors showing improved PFS and OS when treated with panitumumab-FOLFOX4 or cetuximab.	24024839, 18946061
GIMR	2020-05-15	FL	R1	NTRK1	F589L, A608D, G595R, G667C, G667S	Solid tumours	Larotrectinib	Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.	10.1158/1538-7445.AM2016-LB-118
GIMR	2020-04-30	FL	R1	NTRK1	G595R, G667C	Solid tumours	Entrectinib	Blacklisted by FDA approval. Review discussing NTRK fusion-positive cancers, detection methods, and treatment with TRK inhibitors, highlighting resistance mediated by NTRK kinase domain mutations and potential overcoming by second-generation TRK inhibitors.	30333516
GIMR	2020-05-15	FL	R1	NTRK2	Q596E, Q596P, G623S, F633L	Solid tumours	Larotrectinib	Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.	10.1158/1538-7445.AM2016-LB-118
GIMR	2020-04-30	FL	R1	NTRK3	G623R	Solid tumours	Entrectinib	Blacklisted by FDA approval. Review discussing NTRK fusion-positive cancers, detection methods, and treatment with TRK inhibitors, highlighting resistance mediated by NTRK kinase domain mutations and potential overcoming by second-generation TRK inhibitors.	30333516
GIMR	2020-05-15	FL	R1	NTRK3	G623R, G696A, F617L, F617L, F617C, F617I	Solid tumours	Larotrectinib	Blacklisted by FDA approval. Preclinical study. Identified TRKA and TRKB kinase domain mutations (e.g., TRKA V573M, F589L/C, and TRKB Q596E/P, F617L/C/I) that confer resistance to pan-TRK inhibitor LOXO-101.	10.1158/1538-7445.AM2016-LB-118
GIMR	2020-05-21	FL	R2	ABL1	A337V, P465S	Chronic myelogenous leukaemia	Asciminib	Preclinical and phase 1 studies showed that asciminib, an allosteric ABL1 inhibitor, targets both native and mutated BCR-ABL1, including the gatekeeper T315I mutant, and has distinct resistance mutations, including A337V and P465S, compared to catalytic-site ABL1 kinase inhibitors.	28329763, 31826340
GIMR	2024-10-05	FL	R2	ABL1	BCR-ABL1 Fusion	Acute myeloid leukaemia	Gilteritinib	Secondary FLT3-F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression to Gilteritinib.	31088841
GIMR	2025-06-22	FL	R2	AKT1	E17K	Solid tumours except Breast cancer, Endometrial cancer	Ipatasertib	Phase 2 TAPISTRY trial. NCT04589845. N=50. Ipatasertib showed antitumor activity in patients with AKT1/2/3 mutation-positive tumors (majority AKT1 E17K), with ORR of 31.3% (15/48) and median DOR of 14.6 months, driven by responses in endometrial (100%), breast (33%), and head and neck (50%) cancers.	10.1200/JCO.2024.42.16_suppl.3092
GIMR	2021-12-17	FL	R2	AKT1	Oncogenic mutations	Endometrial cancer	LY3023414	Phase 2 study. NCT02684032. N=28. LY3023414 showed modest activity in patients with advanced endometrial cancer harboring PI3K pathway mutations, with ORR 16%, CBR 28%, median PFS 2.5 months, and median OS 9.2 months.	31880826
GIMR	2020-04-25	FL	R2	ALK	Amplification	Non-small cell lung cancer	Crizotinib	Studies identified multiple mechanisms of resistance to ALK tyrosine kinase inhibitors, including secondary mutations in the ALK TK domain, ALK gene amplification, and aberrant activation of other kinases such as KIT and EGFR.	22323827, 22277784
GIMR	2020-04-25	FL	R2	ALK	C1156Y, Fusion and Amplification, L1196M, S1206Y, G1269A, T1151ins	Non-small cell lung cancer	Crizotinib	Retrospective study. ALK-positive NSCLC. Median PFS on sequential crizotinib and ceritinib was 17.4 months, with ceritinib showing significant antitumor activity even after crizotinib treatment, and no difference in PFS on ceritinib between patients with or without ALK resistance mutations. Updated 2025-06-14	25724526
GIMR	2023-08-24	FL	R2	ALK	EML4-ALK fusion	Colorectal adenocarcinoma	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2023-12-09	FL	R2	ALK	EML4-ALK fusion	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2021-06-25	FL	R2	ALK	EML4-ALK fusion	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2021-03-04	FL	R2	ALK	F1174L, F1174V, Amplification	Neuroblastoma	Crizotinib	Phase 2 study. ADVL0912. Crizotinib showed limited activity in patients with ALK-aberrant relapsed/refractory neuroblastoma, with an ORR of 15%, and resistance was associated with specific ALK mutations such as F1174L and F1174V, and ALK amplification.	33568345
GIMR	2020-06-10	FL	R2	ALK	Fusion	Non-small cell lung cancer	Osimertinib	Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy revealed EGFR T790M mutation (63%), MET amplification (5%), HER2 amplification (13%), and small cell transformation (3%) as resistance mechanisms, including ALK fusion as an off-target resistance mechanism.	23470965
GIMR	2021-03-12	FL	R2	ALK	Fusion	Non-small cell lung cancer	Pembrolizumab; Atezolizumab; Nivolumab; Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	IMMUNOTARGET registry. Retrospective study. N=551. Patients with advanced NSCLC and oncogenic driver alterations treated with ICI monotherapy. Objective response rate (ORR) varied by driver alteration: ALK=0%, EGFR=12%, KRAS=26%, BRAF=24%. Median PFS=2.8 months, OS=13.3 months. Notable lack of response in ALK fusion group.	31125062
GIMR	2020-04-25	FL	R2	ALK	Fusion AND Amplification, L1196M, C1156Y, F1174L, F1174V, G1202R, G1269A, I1171T, I1171S, L1152R, L1152V, T1151R, T1151M, L1198F, S1206F, D1203E	Non-small cell lung cancer	Crizotinib	Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.	31628085
GIMR	2021-03-04	FL	R2	ALK	G1128A, E1129V, L1122V, C1156Y, D1160H, F1174, R1192P, L1196M, L1198F, G1202R, G1269A	Non-small cell lung cancer	Crizotinib	Resistance listed for groups EXP2/EXP3A (crizotinib) only. For EXP(3B-5), exposure to individual drugs was not detailed in the publication.	30892989
GIMR	2024-07-03	FL	R2	ALK	G1202R	Non-small cell lung cancer	APG-2449	Preclinical study. APG-2449 is a ALK/ROS1/FAK inhibitor	35820889
GIMR	2020-06-13	FL	R2	ALK	G1202R, G1202del	Non-small cell lung cancer	Ensartinib		31857951
GIMR	2020-05-27	FL	R2	ALK	G1202R, G1202del	Non-small cell lung cancer	Entrectinib		28122866
GIMR	2020-05-27	FL	R2	ALK	G1202R, G1202del, D1203N, E1210K, E1210K and S1206C, E1210K and D1203N	Non-small cell lung cancer	Brigatinib		28122866, 28435288, 29935304
GIMR	2025-04-30	FL	R2	ALK	G1202R, I1171N, I1171S, I1171T, L1196M, L1196Q, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, I1171N and D1203N, F1174L	Solid tumours; Non-small cell lung cancer	Lorlatinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	R2	ALK	G1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196M, L1196Q, L1196Q, D1203N, S1206F, S1206Y, E1210K, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N, F1174L	Solid tumours; Non-small cell lung cancer	Crizotinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	R2	ALK	G1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196Q, G1202del, D1203N, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, I1171N and D1203N, F1174L	Solid tumours; Non-small cell lung cancer	Ceritinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	R2	ALK	G1202R, T1151insT, C1156Y, I1171N, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N, F1174L	Solid tumours; Non-small cell lung cancer	Brigatinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	R2	ALK	G1202R, T1151insT, I1171N, I1171S, I1171T, V1180L, L1196M, L1196Q, L1196Q, L1198F, G1202del, G1269A, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and L1198F, I1171N and D1203N, F1174L	Solid tumours; Non-small cell lung cancer	Alectinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2025-04-30	FL	R2	ALK	G1202R, T1151insT, I1171S, I1171T, L1196Q, G1202del, E1210K, G1269A, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N	Solid tumours; Non-small cell lung cancer	Ensartinib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2021-04-24	FL*	R2	ALK	G1269S	Non-small cell lung cancer	Crizotinib	Cell line assays comparing Zotizalkib against approved ALK inhibitors	10.1158/1538-7445.AM2020-5226
GIMR	2020-04-27	FL	R2	ALK	I1151ins, L1152R, C1156Y, F1174L, F1174V, L1198F, L1196M, L1198P, G1202R, G1202del, S1206Y, G1269A, D1203N	Non-small cell lung cancer	Crizotinib		21030459, 28050598, 26698910, 28122866, 26568289, 22277784
GIMR	2020-04-27	FL	R2	ALK	I1151ins, L1152R, L1152P, C1156Y, C1156T, F1174C, F1174L, F1174V, G1202R, G1202del	Non-small cell lung cancer	Ceritinib	Targeting ALK TKIs is limited by resistance, with diverse mechanisms identified, informing novel therapeutic strategies, including development of inhibitors like JH-VIII-157-02 that overcome G1202R mutation.	28050598, 28122866, 26568289
GIMR	2025-04-30	FL	R2	ALK	I1171N and D1203N	Solid tumours; Non-small cell lung cancer	Neladalkib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2021-04-24	FL*	R2	ALK	I1171N, G1202R, G1202del	Non-small cell lung cancer	Alectinib	Cell line assays comparing Zotizalkib against approved ALK inhibitors	10.1158/1538-7445.AM2020-5226
GIMR	2020-04-27	FL	R2	ALK	I1171T, I1171ins, I1171N, I1171S, V1180L, G1202R, G1202del	Non-small cell lung cancer	Alectinib		28050598; 28122866; 25228534; 26568289; 29935304
GIMR	2021-04-24	FL*	R2	ALK	L1196M and L1198F, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A	Non-small cell lung cancer	Crizotinib	Cell line assays comparing Zotizalkib against approved ALK inhibitors	10.1158/1538-7445.AM2020-5226
GIMR	2021-04-24	FL*	R2	ALK	L1196M and L1198F, L1198F and C1156Y, C1156Y and G1202R, L1196M and G1202R, L1198F and G1202R, G1202R and G1269A	Non-small cell lung cancer	Alectinib; Brigatinib; Ceritinib; Lorlatinib	Cell line assays comparing Zotizalkib against approved ALK inhibitors	10.1158/1538-7445.AM2020-5226
GIMR	2022-09-19	FL	R2	ALK	L1196M, C1156Y	Solid tumours	Crizotinib	Preclinical study. CH5424802, a selective ALK inhibitor, demonstrated antitumor activity against cancers with ALK gene alterations and inhibited the resistant gatekeeper mutant ALK L1196M.	21575866
GIMR	2020-05-27	FL	R2	ALK	L1198F and C1156Y	Non-small cell lung cancer	Lorlatinib	Targeting ALK in ALK-rearranged malignancies is limited by emergence of drug resistance, with diverse mechanisms of resistance discovered, informing development of novel therapeutic strategies to overcome resistance.	28122866
GIMR	2021-04-24	FL*	R2	ALK	L1198F, G1202R	Non-small cell lung cancer	Ceritinib	Cell line assays comparing Zotizalkib against approved ALK inhibitors	10.1158/1538-7445.AM2020-5226
GIMR	2020-04-27	FL	R2	ALK	NPM-ALK fusion	Anaplastic large cell lymphoma 	Crizotinib	Review articles. ALK-rearranged malignancies and mechanisms of resistance to ALK tyrosine kinase inhibitors..	28050598, 28122866
GIMR	2024-06-09	FL	R2	ALK	Oncogenic mutation	Colorectal adenocarcinoma	Panitumumab + FOLFOX	Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months).	10.1200/JCO.2024.42.16_suppl.3507
GIMR	2025-04-30	FL	R2	ALK	T1151insT, I1171N, I1171S, I1171T, V1180L, D1203N, I1171N and D1203N	Solid tumours; Non-small cell lung cancer	Zotizalkib	Preclinical study. NVL-655 is a brain-penetrant tyrosine kinase inhibitor with broad activity against diverse ALK mutations, including lorlatinib-resistant compound mutations, demonstrating high selectivity for ALK over 96% of the kinome.	39269178
GIMR	2022-03-09	FL	R2	ALK	T1151K	Non-small cell lung cancer	Crizotinib	Case report. Secondary mutation for ALK resistance mutation 	30519133
GIMR	2020-04-25	FL	R2	AR	Amplification	Prostate cancer	Anti-androgen	Clinical cohort studies. Plasma DNA analysis demonstrates that androgen receptor (AR) gene aberrations, including copy number gain and point mutations (T878A, L702H, F876L, H874Y, T877A), are associated with resistance to abiraterone and enzalutamide in castration-resistant prostate cancer patients, predicting poor treatment outcomes and survival.	25712683, 26537258
GIMR	2020-04-16	FL	R2	AR	AR-V7	Prostate cancer	Abiraterone acetate; Enzalutamide; Androgen receptor antagonist; CYP17A1 inhibitor	Phase 2. Detection of AR-V7 circulating tumour cells in metastatic castration resistant prostate cancer patients treated with enzalutamide or abiraterone showed a significant lower PFS, OS, and response rate compared to those without AR-V7.	25184630
GIMR	2020-04-26	FL	R2	AR	F877L	Prostate cancer	Enzalutamide; Apalutamide		23842682, 26563462
GIMR	2020-04-26	FL	R2	AR	H875Y, F877L, T878A, T878S, T878A and S889G, F877L and T878A, H875Y and T878A	Prostate cancer	Apalutamide		26813233
GIMR	2020-04-26	FL	R2	AR	H875Y, F877L, T878A, T878S, T878A and S889G, T878A and D891H, F877L and T878A, H875Y and T878A	Prostate cancer	Enzalutamide		26813233
GIMR	2020-04-26	FL	R2	AR	L702H, V716M, V731M, W742L, W742C, H875Y, H875Q, F877L, T878A, T878S, D880E, L882I, S889G, D891H, E894K, M896V, M896T, E898G, T919S, H875Q and T919S, T878A and S889G, T878A and D891H, H875Y and T878A	Prostate cancer	Flutamide		26813233
GIMR	2020-04-26	FL	R2	AR	L702H, V716M, V731M, W742L, W742C, H875Y, H875Q, T878A, T878S, D880E, L882I, S889G, D891H, E894K, M896V, M896T, T919S, H875Q and T919S, T878A and S889G, T878A and D891H, F877L and T878A, H875Y and T878A	Prostate cancer	Bicalutamide		26813233
GIMR	2020-04-26	FL	R2	AR	L702H, W742C, H875Y, T878A	Prostate cancer	Androgen receptor antagonist; GnRH agonist; CYP17A1 inhibitor		26563462
GIMR	2021-10-12	FL	R2	AR	Overexpression	Salivary gland cancers	Enzalutamide	Phase 2. NCT02749903. N=46. ORR 4% (2/46). At 12 months: OS rate 66%, PFS rate 24%. Median PFS was 5.5 months.	10.1200/JCO.2019.37.15_suppl.6020
GIMR	2021-06-07	FL	R2	ARAF	G377R, G387D, G387R, G387S, P462L, Overexpression	Solid tumours	Belvarafenib	Activating ARAF mutation propagates MAPK signaling through dimer- and a kinase activity-dependent mechanism, bypassing inhibition of RAF dimer inhibition.	33953400
GIMR	2026-03-05	FL	R2	ARAF	R544L	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2022-03-10	FL	R2	ARID1A	Loss-of-function mutations, Truncating mutations	Pancreatic adenocarcinoma	Olaparib	Phase 2 single arm study. NCT02677038 and NCT02511223. 0/ 3 responder in the DDR-GA cohort	33662100
GIMR	2023-10-12	FL	R2	ARID1A	Oncogenic mutation	Ovarian Cancer	PLX2853; PLX2853 + carboplatin	Phase 1b/IIa trial. NCT02794586. N=37. PLX2853 monotherapy and combination therapy with carboplatin demonstrated a best ORR of 1 PR (7%). The trial did not meet the prespecified response criteria.	37797273
GIMR	2025-06-30	FL	R2	ARID1A	Oncogenic mutation	Solid tumours; Leiomyosarcoma 	Berzosertib	Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit.	39453756
SuboKB	2020-06-15	ST/FL	R2	ARID1A	Oncogenic mutations	Breast cancer	Fulvestrant	Preclinical study. ARID1A inactivation determines resistance to ER degrader fulvestrant by promoting a switch from ER-dependent luminal cells to ER-independent basal-like cells, mediated by loss of ARID1A-dependent SWI/SNF complex targeting to luminal lineage-determining transcription factors.	31932695
GIMR	2025-03-02	FL	R2	ARID1A	Oncogenic mutations	Colorectal adenocarcinoma	Cetuximab	Retrospective and correlative studies. ARID1A mutations confer intrinsic and acquired resistance to cetuximab treatment in colorectal cancer. Worse treatment outcome observed in patients with ARID1A mutations treated with cetuximab-containing therapies.	36117191
GIMR	2021-03-16	FL	R2	ARID1A	Oncogenic mutations	Pancreatic adenocarcinoma	Olaparib	Two Phase 2 studies of Olaparib in previously treated pancreatic cancer with BRCAness; DDR-GAs subset (N=24) had higher median PFS (5.7 months) and OS (13.6 months); ARID1A (N=3) was among the DDR-GAs identified.	33662100
GIMR	2021-11-05	FL	R2	ARID1A	Oncogenic mutations AND NOT Loss of protein expression	Solid tumours	Ceralasertib + Olaparib	Phase 2. Interim result from NCT03682289. N=10 in the ARID1A-intact cohort (defined as positive IHC staining for BAF250a). ORR 0% (0/10) with best response of SD in 4/10 patients.	10.1016/j.annonc.2021.08.1034
GIMR	2022-03-10	FL	R2	ATM	Loss-of-function mutations, Truncating mutations, Loss-of-protein expression	Pancreatic adenocarcinoma	Olaparib	Phase 2 single arm study. NCT02677038 and NCT02511223. No responders in 5 patients in the loss-of-protein expression group.	33662100
GIMR	2023-12-05	FL	R2	ATM	Oncogenic mutation	Solid tumour	Ipilimumab + Nivolumab	Phase 2. TAPUR study. NCT02693560. N=29. ORR and PFS for nivolumab + ipilimumab in patients with ATM mutation (ORR 14%, DC rate 24%) did not meet the prespecified endpoints. 	38039429
GIMR	2025-06-30	FL	R2	ATM	Oncogenic mutation	Solid tumours; Synovial sarcoma; Non-small cell lung cancer; Pancreatic adenocarcinoma; Ovarian cancer	Berzosertib	Phase 2 trial. NCT03718091. T2 cohort. N=6. ATM-mutant solid tumors treated with Berzosertib had a median PFS of 62 days. No response was seen with stable disease as best response in some patients.	39453756
GIMR	2020-05-30	FL	R2	ATM	Oncogenic mutations	Breast cancer	Olaparib	Phase 2 TBCRC048 study. Olaparib showed efficacy in metastatic breast cancer with gPALB2 (ORR 82%, median PFS 13.3 months) and sBRCA1/2 (ORR 50%, median PFS 6.3 months) mutations, but not in ATM or CHEK2 mutations alone.	33119476, 10.1200/JCO.2020.38.15_suppl.1002
GIMR	2021-03-16	FL	R2	ATM	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. Phase 2. Talazoparib showed limited efficacy in homologous recombination repair-deficient squamous cell lung cancer with ORR of 4% in primary analysis population and 11% in full eligible population. 	33583720
GIMR	2020-06-08	FL	R2	ATM	Oncogenic mutations	Prostate cancer	Olaparib	Retrospective study. Men with metastatic castration-resistant prostate cancer harboring ATM mutations had inferior outcomes to olaparib treatment compared to those with BRCA1/2 mutations, with 0% PSA response (0/6) versus 76% (13/17) and median PFS 2.4 months versus 12.3 months.	30797618
GIMR	2020-12-11	FL	R2	ATM	Oncogenic mutations	Prostate cancer	Olaparib	Updated: PROFOUND trial: No overall PFS difference in ATM subgroup, although benefits in patients previously treated with a taxane was noted (not sufficiently powered).	32343890, 32955174
GIMR	2020-06-08	FL	R2	ATM	Oncogenic mutations	Prostate cancer	Rucaparib	No radiographic or PSA responses in TITRON2	32086346
GIMR	2026-02-02	FL	R2	ATM	Oncogenic mutations	Solid Tumours	Olaparib	Phase 2. Belgian Precision.  No clinical activity observed in ATM (n=13) or CHEK2 (n=14) cohorts.	37852034
GIMR	2023-11-27	FL	R2	ATM	Oncogenic mutations (germline), Oncogenic mutations	Solid tumour except Breast cancer	Talazoparib	Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.	36253484
GIMR	2021-03-16	FL	R2	ATM	Oncogenic mutations, Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Olaparib	Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. In ATM subgroup, response was seen in 1/14 patients with ATM mutation (somatic)	33662100
GIMR	2023-11-27	FL	R2	ATR	Oncogenic mutation	Solid tumour except Breast cancer	Talazoparib	Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.	36253484
GIMR	2021-03-16	FL	R2	ATR	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. Phase 2. Talazoparib showed limited efficacy in homologous recombination repair-deficient squamous cell lung cancer with ORR of 4% in primary analysis population and 11% in full eligible population. 	33583720
GIMR	2025-06-30	FL	R2	ATRX	Oncogenic mutation	Leiomyosarcoma; Osteosarcoma	Berzosertib	Phase 2 trial. NCT03718091. Cohort T1: ATRX-mutant leiomyosarcoma. N=10. Median PFS was short (62 days) with progressive disease as best response in most patients. Evidence of target engagement by berzosertib was seen, but PFS did not correlate with pCHK1 or other pharmacodynamic biomarkers. Increased SLFN11 expression on-treatment correlated with longer PFS (61 vs 33 days).	39453756
GIMR	2020-04-26	FL	R2	AURKA	Amplification	Prostate cancer	Androgen receptor antagonist; GnRH agonist; CYP17A1 inhibitor; Enzalutamide; Apalutamide		26563462
GIMR	2022-09-02	FL	R2	B2M	Loss-of-function mutations, deletion	Melanoma	Pembrolizumab	Case series. Acquired B2M mutation leads to loss of MHC class I expression.	27433843
GIMR	2020-11-26	FL	R2	BAP1	Loss-of-function mutations	Chronic myelogenous leukaemia	Nilotinib; Dasatinib; Ponatinib	Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance	30442766
GIMR	2020-07-02	FL	R2	BAP1	Loss-of-function mutations	Mesothelioma	Olaparib; Talazoparib	Preclinical study. Mesothelioma cells' sensitivity to PARP inhibitors is not dependent on BAP1 status, but is enhanced by temozolomide in cells with high Schlafen 11 and low O6-methylguanine-DNA methyltransferase expression, indicating a potential beneficial combination therapy for patients with specific tumor expression profiles.	32004714
GIMR	2022-06-04	FL	R2	BAP1	Oncogenic mutations	Solid tumours except Mesothelioma	Niraparib	Phase 2 trial. NCT03207347. Niraparib showed limited activity in patients with BAP1 with ORR of (1/18) 6% but clinical benefit was observed in 78% of patients with confirmed mBAP1 tumor, suggesting potential utility in DDR pathway-deficient neoplasms with confirmed mBAP1.	39626160, 10.1200/JCO.2022.40.16_suppl.3122
GIMR	2022-02-02	FL	R2	BAP1	Oncogenic mutations, Loss-of-function mutations, Deletion	Mesothelioma	Olaparib	Phase 2. NCT03531840. Olaparib has no activity in previously treated mesothelioma harbouring BAP1 mutations, except for a sole responder with concomitant germline MRE11A mutation. MRE11A is not in the inclusion criteria.	34661178
GIMR	2023-03-08	FL	R2	BAP1	Oncogenic mutations; Loss-of-function mutations; Deletion	Cholangiocarcinoma; Uveal melanoma; Mesothelioma; Clear cell renal cell carcinoma	Niraparib	NCT03207347. Phase 2. Cohort A. ORR 6% (1/18) failed to meet the primary endpoint and stopped at the first stage of Simon’s design.	10.1200/JCO.2022.40.16_suppl.3122
GIMR	2020-04-25	FL	R2	BCL2	G101V, D103Y, A113G	Chronic lymphocytic leukaemia	Venetoclax	Retrospective case reports, Novel BCL2 mutations, including G101V, were identified in venetoclax-resistant CLL patients, conferring resistance by reducing the affinity of BCL2 for venetoclax and providing a potential biomarker for impending clinical relapse.	32232486, 30514704, 31004028
SuboKB	2020-04-16	FL	R2	BCL2L1	Amplification	Solid tumours	S63845	Mostly resistant in solid tumours	27760111
GIMR	2020-05-19	FL/SO	R2	BCL2L11	Deletion	Non-small cell lung cancer	Gefitinib; Erlotinib	A common intronic deletion polymorphism in the BIM gene confers intrinsic resistance to tyrosine kinase inhibitors (TKIs) in CML and EGFR NSCLC by expressing BIM isoforms lacking the pro-apoptotic BH3 domain, leading to inferior responses to TKIs, but this resistance can be overcome with BH3-mimetic drugs.	22426421
GIMR	2021-10-19	FL	R2	BRAF	A400V, G464V, Y519F, E375D, G466V, I326V, G464E, N581S, V226M, L597R, K601N, G469A, G469A, N581Y, G569R	Solid tumours	Vemurafenib	Class II mutations. A cell line study demonstrating lack of sensitivty to vemurafenib.	26732095
GIMR	2023-12-09	FL	R2	BRAF	Amplification, V600E	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2023-09-11	FL	R2	BRAF	BRAF-CREB3L2 rearrangement, amplification	Low-grade spindle cell neoplasm; Solid tumour	Larotrectinib	Case report. Off-target resistance mechanism identified in two pediatric patients with NTRK fusion-positive solid tumors treated with larotrectinib.	37666486
GIMR	2020-04-26	FL	R2	BRAF	Class II mutations, K601E, K601N, K601T, L597Q, L597V, G469A, G469V, G469R, G464V, G464E, Fusions	Solid tumours	Vemurafenib; Dabrafenib	Preclinical study. Class 2 mutations shows insensitivity to Type 1 and half BRAF inhibitors.	28783719
GIMR	2020-09-15	FL	R2	BRAF	Class III mutations, D287, D287H, V459, V459L, G466, G466V, G466E, G466A, S467, S467L, N581, N581S, N581I, D594, D594N, D594G, D594A, D594H, F595, F595L, G596, G596D, G596R	Solid tumours	FORE8394	Class III mutation; insensitive to dimer breaker	30559419
GIMR	2020-04-26	FL	R2	BRAF	Class III mutations, D287H, V459L, G466V, G466E, G466A, S467L, N581S, N581I, D594N, D594G, D594A, D594H, F595L, G596D, G596R	Solid tumours	Vemurafenib; Dabrafenib	Class III mutations. Preclinical study. Tumours with class 3 BRAF mutants, characterized by impaired kinase activity or kinase-dead mutants, are sensitive to inhibition of RAS activation, particularly in the presence of coexistent mechanisms for maintaining RAS activation, such as RAS mutations or receptor tyrosine kinase signalling.	28783719
GIMR	2022-08-07	FL	R2	BRAF	D594N, Oncogenic mutations	Lung adenocarcinoma; Medullary thyroid cancer	Selpercatinib	Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers.	35304457
GIMR	2020-05-15	FL	R2	BRAF	Fusion, AGK-BRAF fusion, PJA2-BRAF fusion	Non-small cell lung cancer	Erlotinib; Osimertinib	Preclinical study and genomic analysis of patient samples. BRAF fusions (AGK-BRAF and PJA2-BRAF) were identified as an off-target mechanism of acquired resistance to EGFR TKI therapy in approximately 2% of EGFR-mutant lung cancer patients, and combined inhibition of EGFR and MEK or BRAF inhibition were shown to be potential therapeutic strategies.	30831205
GIMR	2022-09-07	FL	R2	BRAF	Fusions, FKBP15-BRAF fusion, TARDBP-BRAF fusion, AGK-BRAF fusion, SKAP2-BRAF fusion, CUL1-BRAF fusion, KIAA1549-BRAF fusion	Melanoma	Vemurafenib; Dabrafenib; FORE8394	Preclinical study. BRAF fusion-positive melanoma cell lines showed heterogeneous responses to RAF and MEK inhibitors, with higher expression levels and dimerization domains associated with resistance and paradoxical MAPK pathway activation, while next-generation RAF inhibitors and combination with MEK inhibitors showed increased therapeutic activity.	31618628
GIMR	2021-02-10	FL	R2	BRAF	G464V, Class II mutations	Triple-negative breast cancer	SHP099; RMC-4550	Preclinical study. SLLIP trial. NCT03248089. N=185. BRAF alterations detected in 22 patients (12%), with 82% being non-V600 mutations, and showed varied sensitivity to SHP2 inhibition in vitro. In cell line model for Class 2 mutation showed relative resistance to SHP2 inhibitors.	31533235
GIMR	2021-04-07	FL	R2	BRAF	G469A, G469V, L485F, L525R, L597R, T599_V600TinsT, K601E, Class II mutations	Colorectal adenocarcinoma	Cetuximab; Panitumumab	Retrospective study. Class 2 BRAF mutants had lower ORR compared to Class 3 (8% vs 50%) to anti-EGFR therapy, with 0% ORR in third-and-later lines treatment.	31515458
GIMR	2023-08-24	FL	R2	BRAF	G469A, L597Q, L597R, V600E, K601E	Colorectal adenocarcinoma; Solid tumours	Divarasib	Phase 1 trial. GO42144. NCT04449874. Divarasib. Confirmed response observed in 53.4% NSCLC and 29% colorectal cancer patients with KRAS G12C mutation, with median PFS of 13.1 and 5.6 months, respectively; serial ctDNA assessment identified genomic alterations associated with response and potential acquired and treatment-emergent resistance mechanisms.	37611121
GIMR	2025-05-18	FL	R2	BRAF	G469A, L597R, L597V	Solid tumours	Exarafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2025-05-18	FL	R2	BRAF	G469A, L597R, L597V, G466V	Solid tumours	Naporafenib 	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2021-11-15	FL	R2	BRAF	G569R	Non-small cell lung cancer	Sotorasib	Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models.	34759319
GIMR	2020-05-15	FL	R2	BRAF	K601, K601E	Melanoma	Trametinib	Phase 2 NCI-MATCH trial. NCT02465060 (Subprotocol R). N=32. Trametinib showed limited activity with 3% ORR and 34% clinical benefit rate in patients with BRAF non-V600 mutations or fusions, with median PFS of 1.8 months and median OS of 5.7 months.	31924734
GIMR	2021-11-16	FL	R2	BRAF	K601E	Melanoma	Vemurafenib	Case report. Lack of response to vemurafenib in melanoma carrying BRAF K601E mutation.	31182949
GIMR	2021-10-19	FL	R2	BRAF	L485_P490del	Solid tumours	LY3009120	Class II mutations. BRAF in-frame deletion in the alpha-C helix favour dimerization and is sensitive to LY3009120 but resistant to Vemurafenib	26732095
GIMR	2024-07-31	FL	R2	BRAF	L485_P490delinsF, L485_P490delinsY, L485delinsFS	Solid tumours	Encorafenib, Dabrafenib	Preclinical study. BRAFΔβ3-αC in-frame deletion mutants reveals differences in sensitivitywith RAF inhibitors.	37656784
GIMR	2021-02-10	FL	R2	BRAF	L505H	Melanoma	Vemurafenib	Case report. Class 2 BRAF mutation. Secondary BRAF(L505H) mutation acquired following Vemurafenib treatment, contributing to resistance in metastatic BRAF mutant melanoma patients.	25515853
GIMR	2022-02-09	FL	R2	BRAF	N486_P490del	Solid tumours	Vemurafenib	Preclinical study. Activating in-frame deletions in protein kinases BRAF, EGFR, and HER2 drive cancer, with crystal structures revealing a mechanism of activation and resistance to certain inhibitors, such as vemurafenib.	26996308
GIMR	2024-06-09	FL	R2	BRAF	Oncogenic mutation	Colorectal adenocarcinoma	Panitumumab + FOLFOX	Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months).	10.1200/JCO.2024.42.16_suppl.3507
GIMR	2021-10-06	FL	R2	BRAF	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
GIMR	2021-11-10	FL	R2	BRAF	Oncogenic mutations AND NOT V600	Non-small cell lung cancer	Vemurafenib	Phase 2. AcSé. NCT02304809. BRAF(V600) mutated NSCLC patients treated with Vemurafenib showed an ORR of 44.9% and median PFS of 5.2 months, while BRAF(nonV600) mutated patients had an ORR of 0%.	31959346
GIMR	2021-06-08	FL	R2	BRAF	Oncogenic mutations, Amplification, Fusion, Class I mutation, Class II mutation,  Class III mutation, BCAP29-BRAF fusion, SND1-BRAF fusion, D594G, D594N, G466A, G469A, G469R, G469V, G596C, I617V, K601E, N486_P490del, N581I, V487_P492>A, V600E, V600E , V600K	Solid tumours	Regorafenib	Phase 2. TAPUR. NCT02604757. N=28. Regorafenib did not meet prespecified criteria for activity in patients with solid tumors and BRAF alterations. DCR was 21%. ORR was 7%.	10.1200/PO.23.00527
GIMR	2020-06-10	FL	R2	BRAF	Oncogenic mutations, fusion	Non-small cell lung cancer	Osimertinib	Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy identified EGFR T790M mutation as the most common mechanism (63%), followed by less frequent mechanisms including MET amplification (5%), HER2 amplification (13%), small cell transformation (3%), and BRAF mutations.	23470965
GIMR	2023-12-22	FL	R2	BRAF	T599_V600insT	Melanoma	Vemurafenib	Case series. No response was seen in two patients with BRAF T599dup	35319964
GIMR	2025-05-18	FL	R2	BRAF	V487_P492del, G469A, L597R, L597V, G466V	Solid tumours	Tovorafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2025-05-18	FL	R2	BRAF	V487_P492del, L485_P490del, G469A, L597V	Solid tumours	Plixorafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2025-05-18	FL	R2	BRAF	V487_P492del, N486_P490del, G469A, L597R, L597V, G466V	Solid tumours	Belvarafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2025-05-18	FL	R2	BRAF	V487_P492del, N486_P490del, L485_P490del, L597V	Solid tumours	PF-07709933 	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2020-10-01	FL	R2	BRAF	V600	Colorectal adenocarcinoma	Vemurafenib	Phase 2 VE-BASKET trial. NCT01524978. Vemurafenib showed varying response rates across different BRAF V600 mutation-positive nonmelanoma cancers, with anecdotal responses observed in colorectal cancer patients treated with vemurafenib and cetuximab but not as a single-agent.	26287849
GIMR	2025-02-17	FL	R2	BRAF	V600	Gastrointestinal neuroendocrine carcinoma	Carboplatin + Etoposide; Cisplatin + Etoposide	Retrospective analysis. N=229. BRAF alterations were not associated with response to platinum etoposide in gastrointestinal high-grade neuroendocrine neoplasms.	38909137
GIMR	2022-03-26	FL	R2	BRAF	V600	Pancreatic adenocarcinoma; Colorectal adenocarcinoma	Vemurafenib	VE-BASKET. Phase 2. ORR in colorectal and pancreatic cancers were 0%.	32029534
GIMR	2020-05-04	FL	R2	BRAF	V600E	Colorectal adenocarcinoma	Lapatinib + Trastuzumab	Phase 2 HERACLES trial. EudraCT 2012-002128-33. In treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer, dual-targeted therapy with trastuzumab and lapatinib achieved an objective response in 30% of patients. No response in a patient with BRAF V600E co-mutation.	27108243
GIMR	2020-05-04	FL	R2	BRAF	V600E	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	Phase 2a MyPathway study. NCT02091141. N=57. Pertuzumab + Trastuzumab showed an objective response in 32% of patients with HER2-amplified metastatic colorectal cancer, with one patient achieving complete response and 17 partial responses, indicating a potential therapeutic opportunity. A single patient with BRAF V600E co-mutation had no response.	30857956
GIMR	2020-05-27	FL	R2	BRAF	V600E	Gastric cancer	Trastuzumab	Biomarkers study, Resistance mechanism to Trastuzumab in HER2-positive metastatic gastric cancer, including EGFR/MET/KRAS/PI3K/PTEN mutations and amplifications, predicted poor PFS (2.6 vs 5.2 months) and OS (7.6 vs 16.1 months).	29208673
GIMR	2022-04-09	FL	R2	BRAF	V600E	High-grade gliomas	Selumetinib	NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR.	35363510
GIMR	2021-06-12	FL	R2	BRAF	V600E	Low-grade gliomas; High-grade gliomas	Ulixertinib	Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%.	10.1200/JCO.2022.40.16_suppl.3009
GIMR	2026-03-11	FL	R2	BRAF	V600E	Solid tumours	BBO-11818	Preclinical study. BBO-11818. Potent noncovalent pan-KRAS inhibitor targeting ON and OFF states of KRAS G12D, G12V, and G12C. Potently inhibited MAPK signaling and cellular viability in KRAS-driven cell lines. Produced tumor regressions in KRAS-mutant xenograft models. Enhanced efficacy observed in combination with anti-PD-1, anti-EGFR antibodies, and RAS:PI3Kα breaker.	41790032
GIMR	2021-06-06	FL	R2	BRAF	V600E	Solid tumours	Selumetinib	Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed.	10.1200/JCO.2021.39.15_suppl.10008
GIMR	2020-07-20	FL	R2	BRAF	V600E	Solid tumours	Sonidegib; Vismodegib	Preclinical study. RAS/MAPK pathway activation drives resistance to Smo inhibition and enhances metastatic behavior in Shh pathway-dependent tumors, with evidence of RAS/MAPK activation in secondary squamous cell cancers emerging from antecedent BCC tumors treated with Smo inhibitor.	26130651
GIMR	2020-05-31	FL	R2	BRAF	V600E and Amplification	Melanoma	Selumetinib	Preclinical study. BRAF gene amplification promotes acquired resistance to MEK inhibitors in BRAF V600E mutant cancer cells by increasing phosphorylated MEK abundance, and combined MEK and BRAF inhibition overcomes this resistance mechanism.	21098728
GIMR	2021-02-10	FL	R2	BRAF	V600E and L514V	Glioma	BGB3245	Type II AC-IN/DFG-OUT RAF dimer inhibitor BGB3245	29880583
GIMR	2021-02-10	FL	R2	BRAF	V600E and L514V	Glioma	Vemurafenib; Dabrafenib; FORE8394	Secondary mutation acquired following dabrafenib, inducing BRAF Dimerization	29880583
GIMR	2021-06-25	FL	R2	BRAF	V600E, AKAP9-BRAF fusion	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2022-02-04	FL	R2	BRAF	V600E, Class I mutations, Class II mutations, G469A	Solid tumours	RMC-4550	SHP2 inhibition is active in cancers driven by class 3 BRAF mutants, NF1 loss, and certain KRASG12 mutants, which remain dependent on RAS nucleotide cycling, offering a potential therapeutic strategy for these currently intractable tumors.	30104724
GIMR	2026-03-05	FL	R2	BRAF	V600E, Fusion, K601E, E275D, G469A, G596C, L597R, L597Q	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2024-07-19	FL	R2	BRAF	V600E, L525R	Cholangiocarcinoma	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2025-05-18	FL	R2	BRAF	V600K, V487_P492del, G469A, L597V, G466V	Solid tumours	Encorafenib	Phase 1. NCT05355701. PF-07799933, a brain-penetrant BRAF inhibitor, with or without binimetinib was well-tolerated and showed multiple confirmed responses in patients with treatment-refractory BRAF-mutant solid tumors using a novel pharmacokinetics-informed dose escalation design.	38691346
GIMR	2023-01-18	FL	R2	BRAF+KRAS	BRAF:V600E AND KRAS:G12D, BRAF:V600E AND KRAS:Oncogenic mutations	Colorectal adenocarcinoma	Encorafenib + Cetuximab	Case report. BRAF V600E-mutated metastatic colorectal cancer developed secondary resistance to cetuximab, encorafenib, and binimetinib due to MET amplification, and tertiary resistance to capmatinib and encorafenib due to emergence of MET D1228N mutation and KRAS G12D.	34994629
GIMR	2024-10-04	FL	R2	BRAF+KRAS	BRAF:V600E AND KRAS:Oncogenic mutations, BRAF:V600E AND KRAS:G12, BRAF:V600E AND KRAS:G13, BRAF:V600E AND KRAS:Q61, BRAF:V600E AND KRAS:K117, BRAF:V600E AND KRAS:A146	Colorectal adenocarcinoma	Encorafenib + Binimetinib + Cetuximab; Encorafenib + Cetuximab	Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment.	39313594
GIMR	2021-04-06	FL	R2	BRAF+KRAS	BRAF:V600E AND KRAS:Q61R	Non-small cell lung cancer	Dabrafenib + Trametinib	Phase 2 MATCH-R trial. Acquired resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R mutations, and PTEN frameshift mutation, highlighting MAPK pathway involvement.	32388065
GIMR	2021-04-06	FL	R2	BRAF+MAP2K1	BRAF:V600E AND MAP2K1:K57N	Non-small cell lung cancer	Dabrafenib + Trametinib	Phase 2 MATCH-R trial. Acquired resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R mutations, and PTEN frameshift mutation, highlighting MAPK pathway involvement.	32388065
GIMR	2024-10-04	FL	R2	BRAF+MAP2K1	BRAF:V600E AND MAP2K1:Oncogenic mutations, BRAF:V600E AND MAP2K1:F53, BRAF:V600E AND MAP2K1:K57	Colorectal adenocarcinoma	Encorafenib + Binimetinib + Cetuximab; Encorafenib + Cetuximab	Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment.	39313594
GIMR	2021-07-08	FL	R2	BRAF+MET	Amplification	Colorectal adenocarcinoma	Encorafenib + Binimetinib + Cetuximab; Encorafenib + Cetuximab	Case report: MET amplification was identified as the off-target resistance mechanism to Encorafenib + cetuximab and was sensitive to incorporation of type I c-met inhibitor.	10.1200/PO.21.00107
GIMR	2024-10-04	FL	R2	BRAF+MET	BRAF:V600E AND MET:amplification	Colorectal adenocarcinoma	Encorafenib + Binimetinib + Cetuximab; Encorafenib + Cetuximab	Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment.	39313594
GIMR	2023-01-18	FL	R2	BRAF+MET	BRAF:V600E AND MET:amplification	Colorectal adenocarcinoma	Encorafenib + Cetuximab	Case report. BRAF V600E-mutated metastatic colorectal cancer developed secondary resistance to cetuximab, encorafenib, and binimetinib due to MET amplification, and tertiary resistance to capmatinib and encorafenib due to emergence of MET D1228N mutation and KRAS G12D.	34994629
GIMR	2024-10-04	FL	R2	BRAF+NRAS	BRAF:V600E AND NRAS:Oncogenic mutations, BRAF:V600E AND NRAS:G12, BRAF:V600E AND NRAS:G13, BRAF:V600E AND NRAS:Q61	Colorectal adenocarcinoma	Encorafenib + Binimetinib + Cetuximab; Encorafenib + Cetuximab	Biomarker analysis of the Phase 3 BEACON CRC trial. NCT02928224. Biomarker analysis showed RAS, MAP2K1, and MET alterations were commonly acquired with treatment.	39313594
GIMR	2021-04-06	FL	R2	BRAF+NRAS	BRAF:V600E AND NRAS:Q61R	Non-small cell lung cancer	Dabrafenib + Trametinib	Novel resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R, and PTEN frameshift mutations, highlighting the recurring involvement of the MAPK pathway.	32388065
GIMR	2021-04-06	FL	R2	BRAF+PTEN	BRAF:V600E AND PTEN:Oncogenic mutations	Non-small cell lung cancer	Dabrafenib + Trametinib	Novel resistance mechanisms to BRAF/MEK inhibitors in BRAF(V600E) NSCLC identified, including MEK1 K57N, NRAS Q61R, KRAS Q61R, and PTEN frameshift mutations, highlighting the recurring involvement of the MAPK pathway.	32388065
GIMR	2021-03-16	FL	R2	BRCA1	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. ORR primary population 4%	33583720
GIMR	2021-06-10	FL	R2	BRCA1	Oncogenic mutations	Non-small cell lung cancer	Rucaparib	Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. In BRCA1/2 cohort, ORR 13%	10.1200/JCO.2021.39.15_suppl.9024
GIMR	2022-06-07	FL	R2	BRCA1	Oncogenic mutations	Ovarian cancer	Trabectedin	Phase 3. NCT02993705. MITO-203. In heavily pretreated platinum resistant ovarian cancer that harbours a BRCA mutation or has BRCA phenotypes, Trabectedin does not improve PFS (4.9 vs 4.4 months), OS, or objective response rate over standard chemotherapy (18% vs 22%). Exploratory analysis showed that OS was similar to non-platinum arm (median 15.8 v 16.0 months), and inferior to carboplatin arm (median OS 22.0 months).	10.1200/JCO.2022.40.17_suppl.LBA5504
GIMR	2020-09-28	FL	R2	BRCA1	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Veliparib	Single-agent has no confirmed response	31976786
GIMR	2025-06-10	FL	R2	BRCA1	Promoter methylation	Breast cancer	Olaparib	Phase 2 COMETA-Breast study. NCT03205761. Olaparib showed limited antitumor activity in pretreated advanced triple-negative breast cancer patients with BRCA1/2 promoter methylation, with an ORR of 9% and median PFS of 2 months.	10.1200/JCO.2023.41.16_suppl.1093
GIMR	2025-02-05	FL	R2	BRCA1	Reversion mutations	Breast cancer	Olaparib	Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.	38244928
GIMR	2021-04-16	FL	R2	BRCA1	Reversion mutations	Ovarian cancer	Rucaparib	Retrospective cfDNA analysis: platinum-resistant/refractory HGSOC are associated with decreased clinical benefit from rucaparib with significantly reduced mPFS (9.0 vs 1.8 months).	30425037
GIMR	2025-06-11	FL	R2	BRCA1+ERBB2	BRCA1:Oncogenic mutation and NOT ERBB2:Overexpression and NOT ERBB2:Amplification	Breast cancer	Olaparib	Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer.	21862407
GIMR	2025-06-11	FL	R2	BRCA1+ERBB2	BRCA1:Oncogenic mutation and NOT ERBB2:Overexpression and NOT ERBB2:Amplification	Breast cancer	Olaparib	Phase 2 trial. NCT00679783. Single-arm trial. Olaparib showed objective response rate of 41% in BRCA-mutated ovarian cancer and 24% in non-BRCA-mutated ovarian cancer, but no responses in HER2-negative breast cancer.	21862407
GIMR	2025-01-12	FL	R2	BRCA2	Oncogenic mutation	Prostate cancer	Ipilimumab + Nivolumab	Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies.	39293514
GIMR	2021-03-16	FL	R2	BRCA2	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Lung-MAP Substudy S1400G. ORR primary population 4%	33583720
GIMR	2021-06-10	FL	R2	BRCA2	Oncogenic mutations	Non-small cell lung cancer	Rucaparib	Phase 2 Lung-MAP Sub-Study, S1900A. ORR 7%. In BRCA1/2 cohort, ORR 13%	10.1200/JCO.2021.39.15_suppl.9024
GIMR	2022-06-07	FL	R2	BRCA2	Oncogenic mutations	Ovarian cancer	Trabectedin	Phase 3. NCT02993705. MITO-203. In heavily pretreated platinum resistant ovarina cancer that harbour a BRCA mutation or has BRCA phenotypes, Trabectedin does not improve PFS (4.9 vs 4.4 months), OS, or objective response rate over standard chemotherapy (18% vs 22%). Exploratory analysis showed that OS was similar to non-platinum arm (median 15.8 v 16.0 months), inferior to carboplatin arm (median 22.0 months).	10.1200/JCO.2022.40.17_suppl.LBA5504
GIMR	2020-09-28	FL	R2	BRCA2	Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Veliparib	Phase 2 trial. In patients with pancreas adenocarcinoma and germline BRCA/PALB2 mutation, cisplatin and gemcitabine with or without veliparib showed high response rates (74.1% and 65.2% respectively), with no significant difference between the two arms, suggesting resistance to PARP inhibitor veliparib when used in combination with DNA damaging agents.	31976786
GIMR	2025-06-10	FL	R2	BRCA2	Promoter methylation	Breast cancer	Olaparib	Phase 2 COMETA-Breast study. NCT03205761. Olaparib showed limited antitumor activity in pretreated advanced triple-negative breast cancer patients with BRCA1/2 promoter methylation, with an ORR of 9% and median PFS of 2 months.	10.1200/JCO.2023.41.16_suppl.1093
GIMR	2025-02-05	FL	R2	BRCA2	Reversion mutations	Breast cancer	Olaparib	Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.	38244928
GIMR	2021-04-16	FL	R2	BRCA2	Reversion mutations	Ovarian cancer	Rucaparib	Retrospective cfDNA analysis: platinum-resistant/refractory HGSOC are associated with decreased clinical benefit from rucaparib with significantly reduced mPFS (9.0 vs 1.8 months).	30425037
GIMR	2025-02-16	FL	R2	BRCA2	Reversion mutations	Pancreatic adenocarcinoma	Oxaliplatin	Retrospective analysis of the Phase 2 GOZILA trial. N=702. Reversion mutation of BRCA2 gene was identified in two patients.	39198618
GIMR	2025-04-23	FL	R2	BRCA2	Reversion mutations	Prostate cancer	Olaparib	Biomarker analysis. In patient enrolled in TOPARP-B trial, reversion mutations were identified in 79% of BRCA2/PALB2-mutated tumors, correlating with improved radiological progression-free and overall survival.	39577422
GIMR	2023-11-27	FL	R2	BRIP1	Oncogenic mutation	Solid tumour except Breast cancer	Talazoparib	Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.	36253484
GIMR	2022-04-09	FL	R2	CALB1	High mRNA expression	Dedifferentiated liposarcoma	Selinexor	Phase 2/3. SEAL. NCT02606461. Exploratory RNAseq analysis showed lack of CALB1 expression was associated with longer median PFS with selinexor (6.9 months) compared with placebo (2.2 months). 	35394800
GIMR	2021-06-10	FL	R2	CAMTA1	TAZ-CAMTA1 fusion	Epithelioid haemangioendothelioma	Trametinib 	Phase 2 P10015/SARC033: ORR 0% (0/26) in patients with EHE habouring TAZ-CAMTA1 fusion treated with trametinib. However, 40% patient had SD > 6 months.	10.1200/JCO.2021.39.15_suppl.11503
GIMR	2020-11-10	FL	R2	CCND1	Amplification	Lung squamous cell carcinoma	Palbociclib	Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.	31302234, 33125909
GIMR	2023-09-11	FL	R2	CCND1	Amplification	Solid tumour except Breast cancer	Palbociclib	Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months.	36853016
GIMR	2022-06-24	FL	R2	CCND1	Amplification	Solid tumours	Ribociclib	NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months.	10.1200/PO.18.00383
GIMR	2023-07-04	FL	R2	CCND1	Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Palbociclib	Phase 2. NCT01037790. In patients with previously treated gastroesophageal cancers and CCND1 overexpression, palbociclib monotherapy demonstrated minimal clinical activity and no objective responses were seen.	32692450
GIMR	2020-11-10	FL	R2	CCND2	Amplification	Lung squamous cell carcinoma	Palbociclib	Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.	31302234, 33125909
GIMR	2023-09-11	FL	R2	CCND2	Amplification	Solid tumour except Breast cancer	Palbociclib	Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months.	36853016
GIMR	2020-11-10	FL	R2	CCND3	Amplification	Lung squamous cell carcinoma	Palbociclib	Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.	31302234, 33125909
GIMR	2023-09-11	FL	R2	CCND3	Amplification	Solid tumour except Breast cancer	Palbociclib	Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months.	36853016
GIMR	2022-06-24	FL	R2	CCND3	Amplification	Solid tumours	Ribociclib	NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months.	10.1200/PO.18.00383
POTTR	2020-04-16	FL	R2	CCNE1	Amplification	Breast cancer	Palbociclib; Ribociclib; Abemaciclib	Phase 3 PALOMA-3 trial. Gene expression analysis identified that patients with high CCNE1 mRNA expression had lower efficacy with palbociclib compared to those with low CCNE1 expression. High CCNE1 mRNA expression was associated with relative resistance to palbociclib.	30807234
GIMR	2021-06-10	FL	R2	CCNE1	mRNA expression	Breast cancer	Fulvestrant + Palbociclib	Exploratory analysis from Phase 3 PEARL study: high tumour CCNE mRNA expression is correlated to relevance 	10.1200/JCO.2021.39.15_suppl.1014
GIMR	2020-10-20	FL	R2	CD274	Loss of protein expression	Cervical cancer	Pembrolizumab	KEYNOTE-028. ORR 0% in PD-L1 negative population (CPS < 1%).	30943124
SuboKB	2020-04-25	FL	R2	CDK12	Loss-of-function mutations	Prostate cancer	Olaparib	No RECIST/PSA response in TOPARP-B trial subgroup.	31806540
GIMR	2020-12-10	FL	R2	CDK12	Loss-of-function mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B. PFS 5.1 v 2.2 mo NS. No OS benefit (HR 0.97) in both adjusted and unadjusted analyses.	32343890, 32955174
GIMR	2025-01-12	FL	R2	CDK12	Oncogenic mutation	Prostate cancer	Ipilimumab + Nivolumab	Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the BRCA2 and CDK12 subgroups, DCR was 15% and 19%, respectively, with PFS at 3.5 and 1.6 months, not superior compared to unselected mCRPC patients compared to other studies.	39293514
GIMR	2022-05-25	FL	R2	CDK12	Oncogenic mutations, Loss-of-function mutations	Prostate cancer	Olaparib; Rucaparib	Retrospective study. In CDK12 altered metastatic castrate-resistance prostate cancer, no responses were seen in 11 patients receiving PARP inhibitors olaparib or rucaparib. Comutation profile was unknown.	32462107
GIMR	2025-02-16	FL	R2	CDK4	Amplification	Breast cancer	Palbociclib; Ribociclib; Abemaciclib	Retrospective analysis. N=926. Focal CDK4 amplification, identified in ER+/HER2- metastatic breast cancers, represents a candidate acquired resistance mechanism to CDK4/6 inhibitors, with higher prevalence seen in populations pretreated with CDK4/6 inhibitors.	39090361
GIMR	2022-06-24	FL	R2	CDK4	Amplification	Glioblastoma	Palbociclib	Preclinical study. GBM xenograft cells with p16(INK4a) expression and either CDK4 amplification or RB mutation were resistant to PD0332991, a Cdk4/6 inhibitor, indicating that intact p16-Cdk4-Rb axis is a determinant of resistance to Cdk4/6 inhibition.	22711607
GIMR	2020-11-10	FL	R2	CDK4	Amplification	Lung squamous cell carcinoma	Palbociclib	Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.	31302234, 33125909
GIMR	2023-11-14	FL	R2	CDK4	Amplification	Solid tumour	Palbociclib; Ribociclib	Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations.	37424386
GIMR	2025-07-01	FL	R2	CDK4	Amplification	Solid tumours	Palbociclib	Phase 2. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C. N=43. Palbociclib showed limited activity in CDK4/6-amplified tumors with ORR of 4% (1/25) in centrally confirmed cohort, median PFS 2.0 months and OS 8.8 months; partial responses and stable disease observed only in CDK4-amplified tumors, with CNS tumors noted as potential candidates for further investigation.	39437014
GIMR	2022-06-24	FL	R2	CDK4	Amplification, Oncogenic mutations	Solid tumours	Ribociclib	NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months.	10.1200/PO.18.00383
GIMR	2022-06-24	FL	R2	CDK4	Amplification, Overexpression	Rhabdomyosarcoma	Ribociclib	Preclinical study. CDK4 amplification/overexpression confer reduced susceptibility to CDK4/6 inhibitors in fusion-positive rhabdomyosarcoma cell-line models.	25810375
GIMR	2020-11-10	FL	R2	CDK6	Amplification	Lung squamous cell carcinoma	Palbociclib	Phase 2, Lung-MAP S1400C trial, evaluated palbociclib in patients with cell cycle gene alterations, showing an ORR of 6%, with two partial responses observed in patients with CCND1 amplification, indicating limited efficacy as monotherapy in squamous NSCLC.	31302234, 33125909
GIMR	2023-11-14	FL	R2	CDK6	Amplification	Solid tumour	Palbociclib; Ribociclib	Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations.	37424386
GIMR	2025-07-01	FL	R2	CDK6	Amplification	Solid tumours	Palbociclib	Phase 2. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol Z1C. N=43. Palbociclib showed limited activity in CDK4/6-amplified tumors with ORR of 4% (1/25) in centrally confirmed cohort, median PFS 2.0 months and OS 8.8 months; partial responses and stable disease observed only in CDK4-amplified tumors, with CNS tumors noted as potential candidates for further investigation.	39437014
GIMR	2022-06-24	FL	R2	CDK6	Amplification, Oncogenic mutations	Solid tumours	Ribociclib	NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months.	10.1200/PO.18.00383
GIMR	2022-06-24	FL	R2	CDK6	Amplification, Overexpression	Breast cancer	Ribociclib; Abemaciclib	Preclinical study. In breast cancer cell line models, amplification of CDK6 acquired after exposure to CDK4/6 inhibitors leads to drug resistance, loss of ER signaling, and decrease responsiveness to endocrine therapy.	27748766
GIMR	2022-09-28	FL	R2	CDKN2A	Deletion	Gastrointestinal stromal tumour	Palbociclib	Phase 2. NCT01907607. In patients with advanced GIST refractory to imatinib and sunitinib with CDKN2A loss, palbociclib showed no significant clinical activity with 86% of patients having progressive disease at 4 months and ORR 0%.	30979737
GIMR	2023-09-11	FL	R2	CDKN2A	Deletion	Low-grade glioma; Low-grade spindle cell neoplasm; Solid tumour	Larotrectinib	Case reports. Off-target resistance mechanism identified in two pediatric patients with NTRK fusion-positive solid tumors treated with larotrectinib.	37666486
GIMR	2022-02-21	FL	R2	CDKN2A	Deletion, Loss-of-function mutations	Urothelial carcinoma	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody; Anti-CTLA-4 monoclonal antibody; Anti-PD-1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody; Anti-PD-L1 monoclonal antibody + Anti-CTLA-4 monoclonal antibody	Retrospective analysis of 789 DFCI and 1250 MSKCC cohorts. CDKN2A genomic alterations were associated with reduced benefit from immune checkpoint blockades in urothelial carcinoma. However, results were inconsistent in gastroesophageal adenocarcinoma, head and neck squamous cell carcinoma, melanoma; non-small cell lung cancer, or renal cell carcinoma.	34074656
GIMR	2022-10-16	FL	R2	CDKN2A	Deletion, Oncogenic mutations	Non-small cell lung cancer	Palbociclib	N=29. ORR 3% (1 PR). DCR 31%. Median PFS 8 weeks.	35050752
GIMR	2022-10-16	FL	R2	CDKN2A	Deletion, Oncogenic mutations	Pancreatic adenocarcinoma; Biliary tract cancer	Palbociclib	TAPUR study. N=22 (12 pancreatic, 10 biliary cancer). ORR 0%. Median PFS 7.2 and 7.3 weeks, and median OS 12.4 and 11.1 weeks in pancreatic and biliary cohorts respectively, with CDKN2A loss or mutation treated with palbociclib.	35100714
GIMR	2022-06-24	FL	R2	CDKN2A	Loss-of-function mutations, deletion	Solid tumours	Ribociclib	NCT02187783. Phase 2. N=106. ORR 3%. PFS 1.8 months.	10.1200/PO.18.00383
SuboKB	2020-04-25	FL	R2	CDKN2A	Loss-of-function mutations, Oncogenic mutations	Pancreatic adenocarcinoma; Cholangiocarcinoma; Gallbladder cancer	Palbociclib	TAPUR Study. N=20. Palbociclib monotherapy showed no objective response or stable disease at 16 weeks in patients with pancreatic and biliary cancers with CDKN2A loss or mutation, with median PFS of 7.2 and 7.3 weeks, and median OS of 12.4 and 11.1 weeks respectively.	35100714
GIMR	2023-11-14	FL	R2	CDKN2A	Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations	Solid tumour	Palbociclib; Ribociclib	Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations.	37424386
GIMR	2023-11-27	FL	R2	CHEK2	Oncogenic mutation	Solid tumour except Breast cancer	Talazoparib	Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.	36253484
GIMR	2020-05-30	FL	R2	CHEK2	Oncogenic mutations	Breast cancer	Olaparib	Phase 2 TBCRC 048 study. NCT not specified. N=54. Olaparib showed ORR of 33% and 31% in cohorts 1 and 2 respectively, with responses primarily observed in gPALB2 (ORR 82%) and sBRCA1/2 (ORR 50%) mutations, but not in ATM or CHEK2 mutations alone.	33119476, 10.1200/JCO.2020.38.15_suppl.1002
GIMR	2021-09-09	FL	R2	CHEK2	Oncogenic mutations	Prostate cancer	Talazoparib	TALAPRO-1. Phase 2. N=9. ORR 0%.	34388386
GIMR	2026-02-02	FL	R2	CHEK2	Oncogenic mutations	Solid Tumours	Olaparib	Phase 2. Belgian Precision.  No clinical activity observed in ATM (n=13) or CHEK2 (n=14) cohorts.	37852034
GIMR	2022-04-21	FL	R2	Chromosome	3p25.3 copy number gain	Nonseminoma; Seminoma	Cisplatin	Cell line and retrospective observational studies. In laboratory cell line models and a multi-institutional cohort, copy number gain of chromosome cytoband 3p25.3 is associated with resistance to cisplatin.	35442716
GIMR	2024-11-04	FL	R2	CLDN18	Protein expression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Zolbetuximab; Zolbetuximab + Pembrolizumab	Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed  efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma.	37490286
GIMR	2024-11-04	FL	R2	CRKL	Amplification	Non-small cell lung cancer	Gefitinib	Preclinical study. CRKL amplification induces transformation and EGFR inhibitor resistance, activates SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways in NSCLC lines.	22586683
GIMR	2024-11-04	FL	R2	CRKL	Amplification, Overexpression	Hepatocellular carcinoma	Atezolizumab	Preclinical study. CRKL overexpression attenuates anti-PD-1 efficacy by mobilizing tumor-associated neutrophils in HCC. Blocking CRKL/β-catenin/VEGF alpha and CXCL1 axis using bevacizumab or lenvatinib overcomes anti-PD-1 resistance.	38403027
GIMR	2023-10-23	FL	R2	CTNNB1+KIT	CTNNB1:S33C and KIT:L576P	Melanoma	Imatinib	Preclinical study. In a single patient case report, CTNNB1 mutation was identified in paired biopsy samples from a patient who had an initial response and later developed resistance to imatinib. Ba/F3 cell line model showed that the combination of KIT L576P mutation with CTNNB1 S33C mutation conferred acquired resistance to imatinib.	28421416
MoSTLLy	2023-01-12	XT	R2	CXCR4	S338X	Waldenstroms macroglobulinaemia	Ibrutinib	Reduced response rate compared with CXCR4 WT patients	32931398, 31570491
GIMR	2025-03-02	FL	R2	DHFR	Amplification	Acute lymphoblastic leukaemia	Methotrexate	N=67, ALL patients, DHFR gene amplification (31%) correlated with p53 mutations (P < .001) is a mechanism of acquired resistance to methotrexate.	7605998
GIMR	2021-06-25	FL	R2	EGFR	A289V	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2023-12-09	FL	R2	EGFR	Amplification	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-05-27	FL	R2	EGFR	Amplification	Gastric cancer	Trastuzumab	Case-control study. AMNESIA panel alterations, including EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications, were more frequent in HER2-positive metastatic gastric cancer patients resistant to trastuzumab, and absence of these alterations was associated with longer median PFS (5.2 vs 2.6 months) and OS (16.1 vs 7.6 months).	29208673
GIMR	2020-06-25	FL	R2	EGFR	Amplification	Glioblastoma	Cetuximab	Phase 2 trial of cetuximab in recurrent high-grade glioma showed limited activity, with 5.5% partial response rate and median PFS of 1.9 months, and no significant correlation was found between response and EGFR amplification, indicating potential resistance mechanism unrelated to EGFR gene copy number.	19491283
GIMR	2020-06-11	FL	R2	EGFR	Amplification	Glioblastoma	Dacomitinib	Phase 2 trial of dacomitinib in recurrent glioblastoma with EGFR amplification showed limited single-agent activity, with a median PFS of 2.7 months and PFS6 of 10.6%.	28575464
GIMR	2021-05-11	FL	R2	EGFR	Amplification	Glioblastoma	Dacomitinib	Phase 2: Dacomitinib was not effecitive in EGFR-amplified GBM. A subset experienced a durable, clinically meaningful benefit (2/4 G598V with TTP>=6 months)	10.1200/PO.19.00295
GIMR	2021-05-11	FL	R2	EGFR	Amplification	Glioblastoma	Depatuxizumab mafodotin	INTELLANCE 2/EORTC 1410: Randomized Phase 2 trial. No evidence of efficacy in the monotherapy arm was observed (vs. control arm Temozolomide or Lomustine).	31747009
GIMR	2020-06-11	FL	R2	EGFR	Amplification	Glioblastoma	Gefitinib	Phase 2 trial evaluated gefitinib in newly diagnosed glioblastoma patients, showing no significant improvement in OS or PFS, with no correlation between EGFR status and clinical outcome, indicating potential resistance to gefitinib.	20510539
GIMR	2023-09-11	FL	R2	EGFR	Amplification	Low-grade glioma	Larotrectinib	Case reports. Off-target resistance mechanism identified in two pediatric patients with NTRK fusion-positive solid tumors treated with larotrectinib.	37666486
GIMR	2020-05-31	FL	R2	EGFR	Amplification	Non-small cell lung cancer	Capmatinib; Crizotinib	Preclinical and clinical genomic analysis identified on-target MET kinase domain mutations and off-target mechanisms including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF as drivers of resistance to MET TKIs in MET exon 14-mutant NSCLC.	32034073
GIMR	2021-01-03	FL	R2	EGFR	Amplification	Non-small cell lung cancer	Crizotinib	Case series. EGFR Amplification in three cases	31548343
GIMR	2020-06-11	FL	R2	EGFR	Amplification	Non-small cell lung cancer	Osimertinib		32385709, 28625643
GIMR	2020-03-12	FL	R2	EGFR	Amplification	Non-small cell lung cancer	Osimertinib	Cell line data. Wild type EGFR	28202511
GIMR	2020-06-11	FL	R2	EGFR	Amplification	Solid tumours	Afatinib	Phase 2 study. Five patients in the EGFR amplified, FISH-Positive subgroup had ORR 0%.	23775486
GIMR	2020-06-11	FL	R2	EGFR	Amplification	Solid tumours	Gefitinib	Phase 2 study (N=15) with 1 PR in EGFR-amplified glioblastoma multiforme. ORR 7%. 	32107712
GIMR	2020-06-28	FL	R2	EGFR	Amplification	Solid tumours	Serclutamab Talirine	Phase 1 study. NCT03234712. Serclutamab talirine, an anti-EGFR antibody-drug conjugate, showed a tolerable safety profile but minimal antitumor activity in 24 patients with glioblastoma, with 1 partial response lasting ~33 months and 6 stable disease. Updated 2025-05-27.	36814898
GIMR	2023-05-07	FL	R2	EGFR	C797S	Non-small cell lung cancer	Aumolertinib	The most common mechanisms of resistance to Aumolertinib were acquired EGFR C797S mutation and aberration in PIK3CA bypass track.	10.1016/j.jtho.2022.07.739
GIMR	2020-06-02	FL	R2	EGFR	C797S, C797G	Non-small cell lung cancer	Afatinib		32206559
GIMR	2020-04-16	FL	R2	EGFR	C797S, C797G	Non-small cell lung cancer	Osimertinib		25964297; 30073261; 37938348
GIMR	2020-05-31	FL	R2	EGFR	D761Y	Non-small cell lung cancer	Gefitinib	Acquired resistance	17085664, 18981003
GIMR	2021-07-12	FL	R2	EGFR	E709_T710delinsD, L747P, V774M, F784F, K806E, N826Y, N842S, T847I, V851I	Non-small cell lung cancer	Gefitinib; Erlotinib	No responders in patients harbouring certain uncommon mutations in retrospective series.	21531810
GIMR	2020-09-03	FL	R2	EGFR	EGFR-SEPT14 Fusion	Colorectal adenocarcinoma	Erlotinib	Case report. A patient with colorectal adenocarcinoma harboring a rare EGFR-SEPT14 fusion achieved a partial response to erlotinib, but subsequently developed resistance with the emergence of EGFRvIII mutation.	32162810
GIMR	2023-05-24	FL	R2	EGFR	EGFR:exon 19 deletion and BRAF:V600E	Non-small cell lung cancer	Osimertinib	Cell line study. Combining osimertinib with a BRAF V600E inhibitor had a significant inhibitory effect in a patient derived cell line model.	27923714
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and C797S, Exon 19 deletion and T790M and C797S, L718Q, L718Q and T790M, G724S, G724S and T790M, L747P, L747_K754delInsATSPE, A767insASV, S768dupSVD, S768dupSVD and V769M, D770insNPG, H773insNPH, L858R and L718V, L858R and L718Q, L858R and C797S, L858R and T790M and L718Q, L858R and T790M and C797S	Non-small cell lung cancer	Lazertinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and C797S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, L858R and C797S, L858R and T790M and C797S	Non-small cell lung cancer	Nazartinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and G724S, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, L718Q, L718Q and T790M, A767insASV, L858R and L718V, L858R and L718Q, L858R and C797S, L858R and T790M and L718Q, L858R and T790M and C797S	Non-small cell lung cancer	Osimertinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and C797S, Exon 19 deletion and T854I, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, E709K and G719S, E709K, L718Q, L718V, L718Q and T790M, G719S, G724S, G724S and T790M, I740dupIPVAK, L747P, L747S, S768I and T790M, V769L, R776H, L858R and L718V, L858R and L718Q, L858R and C797S, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Mobocertinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and T854I, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, E709_T710delInsD, E709K and G719S, E709A and G719S, L718Q, L718V, L718Q and T790M, G719A, G719A and L861Q, G719A and R776C, G719A and T790M, G719S and T790M, G724S and T790M, I740dupIPVAK, L747P, L747S, L747_K754delInsATSPE, K757R, A767insASV, S768dupSVD, S768dupSVD and V769M, S768I, S768I and V769L, S768I and V774M, S768I and T790M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, V774M, R776C, T790M, L858R and L718V, L858R and L718Q, L858R and L792H, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Gefitinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and G724S, Exon 19 deletion and L792H, Exon 19 deletion and G796S, Exon 19 deletion and T854I, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q, L718V, L718Q and T790M, G719A and T790M, G719S and T790M, G724S, G724S and T790M, L747_K754delInsATSPE, A767insASV, S768dupSVD, S768dupSVD and V769M, S768I and V769L, S768I and T790M, V769L, D770insNPG, N771dupN, N771dupN and G724S, H773insNPH, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Erlotinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and L792H, Exon 19 deletion and C797S, Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G724S and T790M, L747P, L747S, L747_K754delInsATSPE, A767insASV, S768dupSVD and V769M, S768I, D770insNPG, H773insNPH, V774M, L858R and C797S, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Neratinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G719S and T790M, G724S and T790M, L747_K754delInsATSPE, A767insASV, S768dupSVD and V769M, D770insNPG, N771dupN, N771dupN and G724S, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Dacomitinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and T790M, Exon 19 deletion and T790M and G724S, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G724S and T790M, S768I, S768I and T790M, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Poziotinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2021-10-02	FL	R2	EGFR	Exon 19 deletion and T790M, Exon 19 deletion and T790M and L792H, Exon 19 deletion and T790M and C797S, Exon 19 deletion and T790M and L718V, L718Q and T790M, G724S and T790M, A767insASV, S768dupSVD and V769M, D770insNPG, H773insNPH, T790M, L858R and T790M, L858R and T790M and V843I, L858R and T790M and L718Q, L858R and T790M and L718V, L858R and T790M and L792H, L858R and T790M and C797S	Non-small cell lung cancer	Afatinib	Cell line sensitivity data from mutational screening with Ba/F3 cells expressing the EGFR mutations. Mutations with log(mutant/WT) ratios > 0.25 after drug exposure are listed.	34526717
GIMR	2025-04-30	FL	R2	EGFR	Exon 19 deletion, T790M	Non-small cell lung cancer	Zongertinib	Preclinical study & Case series. Zongertinib, a covalent HER2 TKI, exhibits antitumor activity in HER2-dependent NSCLC xenografts and induces objective responses in HER2-driven cancers, including SDC4-NRG1 fusion-positive cholangiocarcinoma and HER2 V777L-mutant breast cancer. 	39248702
GIMR	2021-12-29	FL	R2	EGFR	Exon 20 insertion and T790M and C797S	Non-small cell lung cancer	Afatinib; Poziotinib; Tarloxotinib	Preclinical study. Cell line study. Tarloxotinib-E showed efficacy against Ba/F3 cells with EGFR exon 20 mutations, but acquired resistance was observed through T790M or C797S secondary mutations, depending on the original EGFR exon 20 mutation.	33710795
GIMR	2020-04-16	FL	R2	EGFR	Exon 20 mutation	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Dacomitinib	On-target resistance	24353160
GIMR	2021-12-29	FL	R2	EGFR	Exon 20 mutation	Non-small cell lung cancer	Tarloxotinib	Phase 2. RAIN-701 NCT03805841, Cohort B. ORR was 0% (N=11) for tumours with EGFR exon 20 mutations.	10.1016/j.annonc.2020.08.2294
GIMR	2021-12-29	FL	R2	EGFR	H773insH	Non-small cell lung cancer	Tarloxotinib	Preclinical study. Cell line study. Tarloxotinib-E showed efficacy against Ba/F3 cells with various EGFR exon 20 mutations, and acquired resistance to tarloxotinib-E was associated with secondary T790M or C797S mutations, influenced by the original EGFR exon 20 mutation.	33710795
GIMR	2023-03-28	FL	R2	EGFR	H773L and V774M	Non-small cell lung cancer	Afatinib	Case report. A rare EGFR H773L/V774M compound mutation in NSCLC showed primary resistance to afatinib, suggesting it may be one of the EGFR-TKI-resistant uncommon EGFR mutations.	31007929
GIMR	2021-12-06	FL	R2	EGFR	Kinase domain duplication AND T790M	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Dacomitinib	Cell line study. EGFR-KDDT790M Ba/F3 cell line. T790M-positive Ba/F3 cell lines were resistant to 1st and 2nd generation EGFR TKIs	33940786
GIMR	2021-12-06	FL	R2	EGFR	Kinase domain duplication AND T790M AND C797S	Non-small cell lung cancer	Osimertinib; Lazertinib 	Cell line study. EGFR-KDDT790M Ba/F3 cell line. C797S in kinase domain 2 was found mediating resistance mechanism against 3rd generation EGFR TKIs.	33940786
GIMR	2020-04-16	FL	R2	EGFR	L718V, L718Q	Non-small cell lung cancer	Osimertinib	Case report. Acquired EGFR L718V mutation identified as a resistance mechanism to osimertinib in a T790M-negative NSCLC patient, providing insight into osimertinib resistance.	31301016
GIMR	2020-04-16	FL	R2	EGFR	L718V, L718Q, L792	Non-small cell lung cancer	Osimertinib	Novel secondary EGFR mutations L718 and L792 confer osimertinib resistance in NSCLC patients, with L718Q conferring the greatest resistance, and parallel or downstream oncogene alterations also contributing to resistance.	29506987
GIMR	2021-03-31	FL	R2	EGFR	L747_A750delinsP	Non-small cell lung cancer	Erlotinib; Osimertinib	Cell line and in silico structural study demonstrating increased sensitivity to afatinib over erlotinib and osimertinib.	31182434
GIMR	2021-07-08	FL	R2	EGFR	L747_A750delinsP	Non-small cell lung cancer	Gefitinib	Case report of primary Gefitinib resistance. TP53 co-mutation was present.	32883519
GIMR	2020-06-08	FL	R2	EGFR	L747P	Non-small cell lung cancer	Osimertinib	Case report. A Chinese woman with stage IV lung adenocarcinoma harboring a rare EGFR L747P mutation showed intrinsic resistance to both gefitinib and osimertinib, highlighting the challenges in treating NSCLC with rare EGFR mutations.	29673089
GIMR	2020-06-08	FL	R2	EGFR	L747P, L747S	Non-small cell lung cancer	Gefitinib; Erlotinib	Preclinical and clinical study. Afatinib showed efficacy in treating lung adenocarcinoma with uncommon EGFR p.L747P and p.L747S mutations with 80% ORR and 11.97 months median PFS, and no patients acquired p.T790M resistance after afatinib failure.	31200815
GIMR	2020-06-02	FL	R2	EGFR	L792H	Non-small cell lung cancer	Afatinib		32206559
GIMR	2021-12-29	FL	R2	EGFR	L858R and C797S	Non-small cell lung cancer	Tarloxotinib	Cell line study.	33710795
GIMR	2024-09-30	FL	R2	EGFR	L858R and T790M and C797S	Non-small cell lung cancer	Erlotinib; Gefitinib; Osimertinib; Mobocertinib		33632773
GIMR	2024-06-09	FL	R2	EGFR	Oncogenic mutation	Colorectal adenocarcinoma	Panitumumab + FOLFOX	Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months).	10.1200/JCO.2024.42.16_suppl.3507
GIMR	2020-04-25	FL	R2	EGFR	Oncogenic mutations	Non-small cell lung cancer	Ensartinib	Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.	31628085
GIMR	2022-04-13	FL	R2	EGFR	Oncogenic mutations	Non-small cell lung cancer	Linsitinib + Erlotinib	Phase 2. Adding linsitinib to erlotinib resulted in inferior survival (8.4 versus 12.4 month).	27686971
GIMR	2021-03-12	FL	R2	EGFR	Oncogenic mutations	Non-small cell lung cancer	Pembrolizumab; Atezolizumab; Nivolumab; Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Meta-analysis of five clinical trials suggest that immune check point blockades confers no survival benefit as second-line therapy.	29270615
GIMR	2020-06-13	FL	R2	EGFR	R451C, G465R, S464L, I491M, ectodomain mutation	Non-small cell lung cancer	Panitumumab	Ectodomain mutations	25623215
GIMR	2023-05-10	FL	R2	EGFR	S492R	Colorectal adenocarcinoma	Cetuximab; Panitumumab; Cetuximab + FOLFIRI; Cetuximab + Irinotecan; Cetuximab + FOLFIRI; FOLFOX + Panitumumab; Fluorouracil + Panitumumab	Retrospective analysis of patients with available samples from ASPECCT showed that 16% of patients in the cetuximab and 1% of patients in the panitumumab developed treatment-emergent EGFR S492R mutation.	10.1200/jco.2015.33.3_suppl.740, 33026965
GIMR	2020-05-27	FL	R2	EGFR	S492R, K467T, G465R, S464L, I491M, ectodomain mutation	Non-small cell lung cancer	Cetuximab	Ectodomain mutations	22270724, 27929064, 25623215
GIMR	2020-05-15	FL	R2	EGFR	S768_D770dup	Non-small cell lung cancer	Afatinib		32412152
GIMR	2021-07-08	FL	R2	EGFR	T751_I759delinsS, S752_I759del	Non-small cell lung cancer	Gefitinib; Erlotinib	Retrospective study. EGFR exon 19 deletion with starting codon of T751or S752 have a comparatively shorter median PFS.	32418166
GIMR	2020-06-02	FL	R2	EGFR	T790M and L792H, T790M and G796R	Non-small cell lung cancer	Osimertinib		32206559
GIMR	2020-05-15	FL	R2	EGFR	T790M, C797S	Non-small cell lung cancer	Poziotinib		32412152, 10.1016/j.jtho.2019.08.1801
GIMR	2020-06-02	FL	R2	EGFR	T790M, C797S, C797G	Non-small cell lung cancer	Dacomitinib		29410323, 32206559
GIMR	2024-09-30	FL	R2	EGFR	T790M, Exon 20 insertion, P772_H773insGNP, A767_V769dup, N771_H773dup, S768_D770dup	Non-small cell lung cancer	Afatinib	Intermediate sensitivities for Afatinib: S768I	33632773
GIMR	2024-09-30	FL	R2	EGFR	T790M, G719A, G719S, S768I, Exon 20 insertion, N771_H773dup, S768_D770dup	Non-small cell lung cancer	Osimertinib		33632773
GIMR	2024-09-30	FL	R2	EGFR	T790M, G719A, G719S, S768I, L861R, L861Q, A763_Y764insFQEA, Exon 20 insertion, P772_H773insGNP, A767_V769dup, N771_H773dup, S768_D770dup	Non-small cell lung cancer	Erlotinib; Gefitinib	Intermediate sensitivities for Erlotinib: G719A, L861R, L861Q, A763_Y764insFQEA	33632773
GIMR	2020-05-04	FL	R2	EGFR	V843I	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Dacomitinib		25057940
GIMR	2020-09-03	FL	R2	EGFR	vIII	Colorectal adenocarcinoma	Erlotinib	Case report. Colorectal adenocarcinoma harboring a rare EGFR-SEPT14 fusion achieved a partial response to erlotinib, an EGFR tyrosine kinase inhibitor, before developing resistance with the emergence of EGFRvIII mutation. Updated 2025-05-27	32162810
GIMR	2022-02-23	FL	R2	EGFR	vIII	Glioblastoma	Lapatinib		19499221
GIMR	2020-10-05	FL	R2	EGFR+ALK	EGFR:Oncogenic mutations and ALK:fusion	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Osimertinib		30957057
GIMR	2021-05-28	FL	R2	EGFR+BRAF	EGFR:Oncogenic mutations and BRAF:V600E	Non-small cell lung cancer	Osimertinib	Case report	33580193
GIMR	2023-02-28	FL	R2	EGFR+CD274	CD274:Protein expression and EGFR:Oncogenic mutations	Non-small cell lung cancer	Pembrolizumab	NCT02879994. Phase 2. The ORR was <9% in in EGFR-Mutant, TKI naive patients treated with pembrolizumab. including PD-L1 expression ≥50%.	29874546
GIMR	2020-05-15	FL	R2	EGFR+EGFR	EGFR:T790M and EGFR:C797S and EGFR:T790M-C797S cis-allelic conformation	Non-small cell lung cancer	Osimertinib	On-target resistance	31075545
GIMR	2020-06-29	FL	R2	EGFR+MET	EGFR:Exon 19 deletion and MET:Exon 14 skipping mutation, EGFR:L858R and MET:Exon 14 skipping mutation	Non-small cell lung cancer	Osimertinib + Crizotinib	Preclinical study. Acquired MET exon 14 alteration drives secondary resistance to EGFR tyrosine kinase inhibitor in EGFR-mutated lung cancer.	31157314
GIMR	2024-08-27	FL	R2	EGFR+MET	EGFR:Oncogenic mutation AND MET:amplification AND MET:D1228, EGFR:Oncogenic mutation AND MET:amplification AND MET:D1230	Non-small cell lung cancer	Osimertinib + Tepotinib	Phase 2. INSIGHT-2.  NCT03940703. N=128. Treatment emergent resistance following Tepotinib + Osimertinib treatment.	39089305
GIMR	2024-08-27	FL	R2	EGFR+MET+ALK	EGFR:Oncogenic mutation AND MET:amplification AND EML4-ALK fusion	Non-small cell lung cancer	Osimertinib + Tepotinib	Phase 2. INSIGHT-2.  NCT03940703. N=128. No response was seen in patients with co-mutations in BRAF, KRAS, and ALK fusions.	39089305
GIMR	2024-08-27	FL	R2	EGFR+MET+BRAF	EGFR:Oncogenic mutation AND MET:amplification AND BRAF:Oncogenic mutation	Non-small cell lung cancer	Osimertinib + Tepotinib	Phase 2. INSIGHT-2.  NCT03940703. N=128. No response was seen in patients with co-mutations in BRAF, KRAS, and ALK fusions.	39089305
GIMR	2024-08-27	FL	R2	EGFR+MET+KRAS	EGFR:Oncogenic mutation AND MET:amplification AND KRAS:Oncogenic mutation	Non-small cell lung cancer	Osimertinib + Tepotinib	Phase 2. INSIGHT-2.  NCT03940703. N=128. No response was seen in patients with co-mutations in BRAF, KRAS, and ALK fusions.	39089305
GIMR	2020-10-05	FL	R2	EGFR+RB1	EGFR:Oncogenic mutations and RB1:Oncogenic mutations	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Osimertinib	Small-cell transformation	25758528, 30550363
GIMR	2020-10-05	FL	R2	EGFR+RET	EGFR:Oncogenic mutations and RET:fusion	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Osimertinib	RET fusions mediate acquired resistance to EGFR tyrosine kinase inhibitors in EGFR-mutant NSCLC, and combined EGFR and RET inhibition with osimertinib and BLU-667 shows promise as a well-tolerated and effective treatment strategy.	30257958, 30957057
GIMR	2020-10-05	FL	R2	EGFR+ROS1	EGFR:Oncogenic mutations and ROS1:fusion, GOPC-ROS1 fusion	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Osimertinib	Case report. GOPC-ROS1 rearrangement identified as an acquired resistance mechanism to osimertinib, with subsequent response to crizotinib combined treatments in lung adenocarcinoma patient.	29935846
GIMR	2020-10-05	FL	R2	EGFR+TP53	EGFR:Oncogenic mutations and TP53:Oncogenic mutations	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Osimertinib	Small-cell transformation	30550363
GIMR	2021-03-08	FL	R2	ERBB2	A775_G776insYVMA (Y772_A775dup)	Non-small cell lung cancer	Dacomitinib	No partial response observed in thirteen patients	25899785
GIMR	2020-05-15	FL	R2	ERBB2	A775_G776insYVMA (Y772_A775dup)	Solid tumours	Dacomitinib		31588020
GIMR	2021-03-17	FL	R2	ERBB2	A775_G776insYVMA (Y772_A775dup)	Solid tumours	Osimertinib	High throughput screening of VUS in ERBB2	29967253
GIMR	2020-06-15	FL	R2	ERBB2	A775_G776insYVMA (Y772_A775dup)	Solid tumours; Non-small cell lung cancer	Afatinib; Dacomitinib		31588020
GIMR	2020-05-15	FL	R2	ERBB2	A775_G776insYVMA (Y772_A775dup), L755P, L869R	Solid tumours	Pyrotinib		31588020
GIMR	2020-05-15	FL	R2	ERBB2	A775_G776insYVMA (Y772_A775dup), L755P, P780ins	Solid tumours	Afatinib		31588020
GIMR	2023-08-24	FL	R2	ERBB2	Amplification	Colorectal adenocarcinoma	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2023-12-09	FL	R2	ERBB2	Amplification	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-06-10	FL	R2	ERBB2	Amplification	Non-small cell lung cancer	Erlotinib; Gefitinib	Off-target mechanism	23470965
GIMR	2022-11-01	FL	R2	ERBB2	Amplification and D769Y	Breast cancer	Lapatinib; Trastuzumab	Xenograft model. Trastuzumab and lapatinib did not show activity in a breast cancer PDX model that harbour both ERBB2 amplification and HER2 D769Y mutation	30301790
GIMR	2025-06-09	FL	R2	ERBB2	Amplification and NOT overexpression	Colorectal adenocarcinoma; Bladder cancer	Trastuzumab deruxtecan	Phase 2 basket trial. NCT02675829. N=88. Trastuzumab Emtansine (TDM1) demonstrated variable activity in multiple HER2-amplified tumor types, with ORR in NSCLC (21.1%), endometrial cancer (21.7%), and salivary gland cancer (87.5%), while colorectal cancer had 0% ORR, and other HER2-amplified solid tumors had 8.7% ORR, including biliary (12.5%), ovarian (14.3%).	10.1200/JCO.2025.43.16_suppl.3020
GIMR	2020-07-02	FL	R2	ERBB2	Amplification, Overexpression	Colorectal adenocarcinoma	Cetuximab; Panitumumab; Cetuximab + Irinotecan	Retrospective biomarker study	10.1200/PO.18.00226
GIMR	2021-03-17	FL	R2	ERBB2	Amplification, Overexpression	Colorectal adenocarcinoma	Trastuzumab Emtansine + Pertuzumab	Phase 2. NCT03225937. HERACLES-B. N=31. The combination did not reach the primary endpoint (ORR 9.7%), but DCR 77.4% with median PFS 4.1mo.	32988996
GIMR	2022-08-26	FL	R2	ERBB2	Amplification, Overexpression	Colorectal adenocarcinoma	Tucatinib	Phase 2. Single-arm study. MOUNTAINEER. NCT03043313. N=31. ORR was 3% in tucatinib monotherapy in metastatic CRC after two-lines of systemic treatment (Cohort C).	10.1016/j.annonc.2022.04.440
GIMR	2022-08-26	FL	R2	ERBB2	Amplification, Overexpression	Solid tumours except Breast cancer, Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma 	Trastuzumab Emtansine	Phase 2. NCT02465060. NCI-MATCH trial (EAY131) subprotocol Q. In 36 patient (of 38) included in efficacy analysis, ORR was 6% (2/36, one salivary gland mucoepidermoid carcinoma and one salivary gland squamous cell cancer) and did not meet the prespecified criteria. PFS at 6-month was 23.6%.	31504139
GIMR	2021-12-29	FL	R2	ERBB2	C805S	Non-small cell lung cancer	Tarloxotinib; Afatinib; Poziotinib; Osimertinib; Pyrotinib	Cell line mutagenesis study identified C805S arising in Ba/F3 cells after treatment with Tarloxotinib and other TKIs. C805S is a secondary mutation, homologous to EGFR C797, that interfere with covalent bonding from the irreversible TKIs.	34584864
GIMR	2023-04-20	FL	R2	ERBB2	ERBB2-GRB7 fusion	Colorectal adenocarcinoma	Afatinib; Trastuzumab; Cetuximab; Cetuximab + irinotecan	Case series. Targetable kinase alterations (RTK alterations and MAP2K1 mutations) identified in 8% of colorectal carcinoma, preferentially associated with wild-type RAS/RAF, and may predict poor response to anti-EGFR therapy.	26660078
GIMR	2023-04-20	FL	R2	ERBB2	ERBB2-GRB7 fusion	Colorectal adenocarcinoma	Trastuzumab	Case report. Retrospective series. Acquired ERBB2-GRB7 fusion in the follow-up was identified on liquid biopsy.	36470901
GIMR	2021-03-11	FL	R2	ERBB2	Exon 16 skipping mutation	Non-small cell lung cancer	Osimertinib	In EGFR L858R/T790M-positive lung adenocarcinoma who developed resistance to osimertinib through an Src-independent pathway.	31557536, 33209639
GIMR	2020-06-15	FL	R2	ERBB2	Exon 20 insertion except G778ins, S779ins, P780ins	Solid tumours; Non-small cell lung cancer	Afatinib; Dacomitinib; Neratinib; Pyrotinib	Preclinical study. ERBB2 mutations characterized across 25 tumor types, with poziotinib showing potent activity against HER2 mutants, and enhancing T-DM1 activity in pre-clinical models, and showing 42% confirmed objective response rate in ERBB2 exon 20-mutant NSCLC patients.	31588020
GIMR	2023-11-22	FL	R2	ERBB2	Exon 20 insertion, T798M, A775_G776insYVMA (Y772_A775dup), G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVC	Solid tumour	Tucatinib	Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells.	10.1158/1538-7445.AM2023-4019
GIMR	2022-11-04	FL	R2	ERBB2	G309A, G309E, S310F, D769H, D769Y, L755S, V777L, V842I, E321G, R896C, P780ins, L755_T759del, R678Q	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	Phase 2. NCT02693535. TAPUR. N=28 in Cohort 2. ORR was 0%. DCR 10%.	36315917
GIMR	2021-03-17	FL	R2	ERBB2	L755M, L755S, A775_G776insYVMA (Y772_A775dup), G776delinsLC, G776delinsVC, S779_P780insVGS, V842I, T862A	Solid tumours	Lapatinib	High throughput screening of VUS in ERBB2	29967253
GIMR	2021-06-16	FL	R2	ERBB2	L755S	Breast cancer	Lapatinib; Neratinib; Tucatinib; Trastuzumab	HER2+ BT474 cell model study	10.1158/1538-7445.SABCS20-PD3-09
GIMR	2020-10-05	FL	R2	ERBB2	L755S	Breast cancer	Tucatinib		10.1158/1538-7445.AM2020-1911
GIMR	2020-10-05	FL	R2	ERBB2	L755S, D769Y, V842I, K753E	Breast cancer	Trastuzumab	Somatic HER2 mutations, such as L755S, V842I, K753I, and D769Y, are associated with resistance to certain anti-HER2 therapies, including trastuzumab and lapatinib, while others like S310F, S310Y, R678Q, D769H, or I767M show activities, and specific mutations like L755S or D769Y may have activity from neratinib or afatinib in HER2-positive breast cancer.	32256585
GIMR	2020-05-15	FL	R2	ERBB2	L755S, L755P	Breast cancer	Trastuzumab Emtansine; Lapatinib + Trastuzumab; Trastuzumab; Lapatinib + Capecitabine; Lapatinib + Letrozole; Lapatinib + Paclitaxel; Trastuzumab + Paclitaxel; Trastuzumab + Pertuzumab + Paclitaxel; Trastuzumab + Capecitabine		28487443
GIMR	2020-05-15	FL	R2	ERBB2	L755S, L755P, A775_G776insYVMA (Y772_A775dup), G778ins, P780_Y781insGSP (G778_P780dup), P780ins, V842I, L869R	Solid tumours	Lapatinib	Preclinical study. ERBB2 mutations characterized across 25 tumor types, with poziotinib showing potent activity against HER2 mutants, and enhancing T-DM1 activity in preclinical models, with a 42% confirmed objective response rate in ERBB2 exon 20-mutant NSCLC patients in Phase 2 clinical testing.	31588020
GIMR	2020-05-15	FL	R2	ERBB2	L755S, L755P, V842I, D769H, V777L	Breast cancer	Lapatinib	L755S. Intermediate resistance for others	23220880
GIMR	2020-10-05	FL	R2	ERBB2	L755S, V842I, K753E	Breast cancer	Lapatinib	Somatic HER2 mutations demonstrate varied therapeutic implications: L755S, V842I, K753I, and D769Y confer resistance to trastuzumab and lapatinib; S310F, S310Y, R678Q, D769H, and I767M are associated with favorable treatment outcomes; L755S and D769Y may respond to neratinib or afatinib.	32256585
GIMR	2022-11-25	FL	R2	ERBB2	Low protein expression	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Trastuzumab deruxtecan	DESTINY-Gastric 01. NCT03329690. Exploratory cohort. In IHC 1+ cohort, ORR was 9.5% (2/21) and did not meet the prespecified endpoint. DCR 71%. 	36379002
GIMR	2021-06-08	FL	R2	ERBB2	No protein expression, Low protein expression	Colorectal adenocarcinoma	Trastuzumab deruxtecan	Phase 2 DESTINY-CRC01. No objective responses seen in cohort B (IHC2+ and ISH-negative) or cohort C (IHC1+).	33961795, 10.1200/JCO.2020.38.15_suppl.4000
GIMR	2020-04-25	FL	R2	ERBB2	Oncogenic mutations	Non-small cell lung cancer	Ensartinib	Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.	31628085
GIMR	2020-04-16	FL	R2	ERBB2	Oncogenic mutations, A775_G776insYVMA (Y772_A775dup), exon 20 insertion	Non-small cell lung cancer	Neratinib	Phase 1/2 SUMMIT trial. NCT01953926. Multi-histology, genomically selected basket trial of neratinib. Only 1 (of 26) responder was seen in non-small cell lung cancer.	29420467
GIMR	2020-11-15	FL	R2	ERBB2	Overexpression	Urothelial carcinoma	Lapatinib	Phase 3 trial. N=232. Maintenance lapatinib did not improve PFS (4.5 vs 5.1 months) or OS (12.6 vs 12.0 months) in HER1/HER2-positive metastatic urothelial bladder cancer patients after first-line chemotherapy, including in patients strongly positive for HER1/HER2.	28034079
GIMR	2023-06-20	FL	R2	ERBB2	Overexpression, Protein expression	Pancreatic adenocarcinoma	Trastuzumab deruxtecan	Phase 2. NCT04482309. DESTINY-PanTumor02	37870536, 10.1200/JCO.2023.41.17_suppl.LBA3000
GIMR	2024-12-02	FL	R2	ERBB2	p95 expression	Breast cancer	Trastuzumab	Preclinical study. HER2-overexpressing breast cancer cells expressing p95HER2 were resistant to trastuzumab, but sensitive to lapatinib, with significant growth inhibition and tumor regression in xenograft models	17440164
GIMR	2024-08-29	FL	R2	ERBB2	Protein expression AND Amplification AND NOT Overexpression	Colorectal cancer	Trastuzumab deruxtecan	Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. Trastuzumab deruxtecan demonstrated an overall response rate (ORR) of 34% (42/122) across two dose groups. The ORR was higher in the HER2 IHC 3+ population (47%, 30/64) but lower in the HER2 IHC 2+ with amplified group (5.6%, 1/18).	39116902
GIMR	2021-03-17	FL	R2	ERBB2	R487W, L755P, L755S, D769Y, A775_G776insYVMA (Y772_A775dup), G776S, G776V, G776delinsLC, G776delinsVC, V777L, G778_S779insG, P780_Y781insGSP (G778_P780dup), L841V, V842I, N857S, T862A, D962N, P1199T	Solid tumours	Trastuzumab	High throughput screening of VUS in ERBB2	29967253
GIMR	2023-04-12	FL	R2	ERBB2	T798I	Breast cancer	Neratinib	Case report. ERBB2 T798I gatekeeper mutation was found in a breast cancer patient after sustained partial response to neratinib.	28274957
GIMR	2020-06-13	FL	R2	ERBB2	T798I, L785F, D769Y	Breast cancer	Neratinib; Fulvestrant + Neratinib	Preclinical and clinical study. HER2 mutations define a targetable breast cancer subset. Concurrent activating HER2 or HER3 alterations and acquisition of multiple HER2-activating events, as well as gatekeeper alterations, were associated with de novo and acquired resistance to neratinib.	31806627
GIMR	2023-11-22	FL	R2	ERBB2	T798M	Solid tumour	ELVN-002	Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells.	10.1158/1538-7445.AM2023-4019
GIMR	2021-05-20	FL	R2	ERBB2	ZNF207-ERBB2 fusion	Gastric cancer	Trastuzumab; Trastuzumab Emtansine	Preclinical study. HER2 fusions (ZNF207-HER2 and MDK-HER2) were identified as oncogenic drivers in gastric cancer, with ZNF207-HER2 fusion not responsive to trastuzumab due to impaired binding.	25889497
GIMR	2022-08-30	FL	R2	ERBB2+ERBB3	ERBB2:Oncogenic mutation and ERBB3:E928G, ERBB2:S310F and ERBB3:E928G, ERBB2:L755S and ERBB3:E928G, ERBB2:V777L and ERBB3:E928G, ERBB2:L869R and ERBB3:E928G	Breast cancer	Neratinib; Trastuzumab + Pertuzumab; Trastuzumab	Cell-line study. HER2/HER3 co-mutations activate both ERBB and PI3K signaling pathways in tumour cells, resulting in resistance to HER2 inhibitors.	34171264
GIMR	2020-05-09	FL	R2	ERBB2+KRAS	ERBB2:amplification and KRAS:G12	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	MyPathway subgroup	30857956
GIMR	2021-06-05	FL	R2	ERBB2+KRAS	ERBB2:Amplification AND KRAS:Oncogenic mutations; ERBB2:Oncogenic mutations AND KRAS:Oncogenic mutations; ERBB2:Overexpression AND KRAS:Oncogenic mutations	Solid tumours	Trastuzumab + Pertuzumab	Phase 2 Basket trial. MyPathway. ORR in KRAS-co-mutations: 1 / 26 (4%).	10.1200/JCO.2021.39.15_suppl.3004
GIMR	2024-08-29	FL	R2	ERBB2+KRAS	ERBB2:Overexpression AND KRAS:Oncogenic mutation, ERBB2:Protein expression AND KRAS:Oncogenic mutation	Colorectal cancer	Trastuzumab deruxtecan	Phase 2 DESTINY-CRC02 trial. NCT04744831. N=122. In the post-hoc analysis, RAS mutations identified by ctDNA (either clonal or subclonal) were associated with a lower response rate (13%) compared to RAS wild-type.	39116902
GIMR	2025-02-16	FL	R2	ERBB2+PTEN	ERBB2:Oncogenic mutations and PTEN:Loss of protein expression, ERBB2:Oncogenic mutations and PTEN:Loss-of-function mutations, ERBB2:Oncogenic mutations and PTEN:Oncogenic mutations, ERBB2:Oncogenic mutations and PTEN:Deletion	Extramammary Paget’s disease	Trastuzumab	Preclinical study. In PDX models, trastuzumab-resistant EMPD model showed PTEN loss as a resistance mechanism.	38987365
GIMR	2020-06-09	FL	R2	ERBB3	A232V	Extramammary Paget’s disease	Trastuzumab	Case report. A patient with ERBB2(S310F) mutated metastatic extramammary Paget's disease initially responded to trastuzumab and carboplatin, but developed resistance with additional genomic alterations including ERBB3(A232V) and PIK3CA(G106V) mutations and MET and CDK6 amplification.	31803359
GIMR	2025-07-01	FL	R2	ERBB3	Amplification	Low-grade serous ovarian cancer	Binimetinib	Case series. KRAS-mutated LGSOC patient with MEK inhibitor resistance developed aggressive brain metastases associated with ERBB3 amplification and aberrant ERBB3–MYC signaling, suggesting potential resistance mechanisms and need for combinatorial strategies.	31836588
GIMR	2020-05-31	FL	R2	ERBB3	Amplification	Non-small cell lung cancer	Capmatinib	Preclinical and clinical genomic analysis identified on-target MET kinase domain mutations and off-target mechanisms including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF as drivers of resistance to MET TKIs in MET exon 14-mutant NSCLC.	32034073
GIMR	2021-12-29	FL	R2	ERBB3	Amplification, Overexpression	Non-small cell lung cancer	Tarloxotinib	Cell line study. ER3 overexpression was identified as a mechanism of resistance to tarloxotinib-E.	34584864
GIMR	2020-09-15	FL	R2	ERBB3	F94L, G284R, D297Y, T355I, E1261A	Breast cancer	Lapatinib	Preclinical study. HER3 mutations (e.g., T355I, F94L, G284R, D297Y, E1261A) were found to be activating and confer resistance to lapatinib in ER+ and HER2+ breast cancer cells, with HER3(T355I) inducing cell proliferation via HER4/HER1-dependent ERK1/2 and cyclinD1 mediated pathways.	29963236
GIMR	2024-06-09	FL	R2	ERBB3	Oncogenic mutation	Colorectal adenocarcinoma	Panitumumab + FOLFOX	Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months).	10.1200/JCO.2024.42.16_suppl.3507
GIMR	2022-11-04	FL	R2	ERBB3	Oncogenic mutations	Colorectal adenocarcinoma	Trastuzumab + Pertuzumab	Phase 2. NCT02693535. TAPUR. N=28 in Cohort 2. ORR was 0%. DCR 10%.	36315917
GIMR	2020-04-25	FL	R2	ERBB3	Oncogenic mutations, R103G, V104L, V104M, G284R, D297Y, T355A, E928G	Solid tumours	Neratinib	Phase 1/2 SUMMIT trial. NCT01953926. Multi-histology, genomically selected basket trial. No response to Neratinib were seen in patients with ERBB3 hotspot mutations.	29420467
GIMR	2021-05-17	FL	R2	ERBB3	Overexpression	Prostate cancer	Patritumab	Cell line and DX model studies. Lack of antitumor activity was demonstrated in vitro HER3-positive prostate cancer cell lines and PDX models through inhibition of HER3 alone.	34753775
GIMR	2022-05-18	FL	R2	ERBB3	Q809R	Solid tumours	Pictilisib	Preclinical study. Oncogenic ERBB3 mutations identified in colon and gastric cancers, with mutant ERBB3 oncogenic activity dependent on ERBB2, suggesting potential resistance to ERBB-targeting therapies unless ERBB2 is also inhibited.	23680147
GIMR	2025-02-03	FL	R2	ERBB3	Truncating mutations,  Y789fs	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1. U31402-A-U102 trial. N=102. In EGFR-mutated NSCLC patients who progressed after EGFR TKI and platinum-based chemotherapy, Patritumab deruxtecan showed confirmed ORR of 41% and median OS 16.2 months.	38369013
SuboKB	2020-04-23	ST	R2	ERBB4	Oncogenic mutations	Head and neck squamous cell carcinoma 	Cetuximab	Preclinical study. Afatinib showed antitumor activity against ESCC and HNSCC cell lines with activating oncogenic EGFR and HER4 mutations, suggesting potential for targeted therapy in patients with such mutations, particularly in HNSCC where HER4 mutations are relatively frequent, indicating a possible resistance mechanism.	27207775
GIMR	2024-10-08	FL	R2	ESR1	D351Y, E380Q, S463P, M528I, L536H, L536P, Y537C, Y537S, Y537D, D538G	Breast cancer	Ribociclib + Letrozole; Ribociclib + Anastrozole; Ribociclib + Tamoxifen; Letrozole; Ribociclib + Letrozole + Goserelin; Ribociclib + Anastrozole + Goserelin; Ribociclib + Tamoxifen + Goserelin; Letrozole; Fulvestrant	Combined biomarker analysis of MONALEESA-2, -3, and -7 trials. Higher prevalences of ESR1 gene alterations was seen in D538, Y537, E380, L536 (with potential candidates at D351, M528).	39313156
GIMR	2021-06-07	FL	R2	ESR1	D538G	Breast cancer	H3B-6545	Phase 1/2: ORR 17% (12/72) at RP2D in heavily pretreated patients and visceral metastases, but ORR 0% (0/17) responses seen in D538G.	10.1200/JCO.2021.39.15_suppl.1018
GIMR	2020-04-26	FL	R2	ESR1	E380Q, V392I, S463P, V534E, P535H, L536R, L536Q, Y537S, Y537N, Y537C, D538G	Breast cancer	GnRH agonist; Aromatase Inhibitor; Letrozole; Anastrozole; Exemestane; Tamoxifen	Review article discusses ESR1 mutations as a mechanism for acquired endocrine resistance in ER-positive breast cancer, occurring in approximately 20% of metastatic patients treated with endocrine therapies.	26122181
GIMR	2022-12-07	FL	R2	ESR1	ESR1-YAP1 fusion, ESR1-PCDH11X fusion, ESR1-SOX9 fusion, ESR1-ARNT2 fusion	Breast cancer	Fulvestrant	Preclinical study. Functionally active ESR1 gene fusions and activating ESR1 LBD point mutations drives endocrine treatment failure and resistance in metastatic breast cancer.	34711608
GIMR	2022-06-17	FL	R2	ESR1	F404L, F404I, F404V, D538G and F404L, E380Q and F404L	Breast cancer	Fulvestrant	Novel ESR1 F404 mutations (F404L, F404I, and F404V) were acquired in 4% of patients in the plasmaMATCH Cohort A trial (NCT03182634, N=69). These mutations confer resistance to fulvestrant when combined with preexisting activating ESR1 mutations. In cell line models, F404L demonstrates sensitivity to tamoxifen and select SERDs. These mutations may be potentially targetable by oral ERalpha degraders in clinical development.	37982575, 10.1200/JCO.2022.40.16_suppl.1009
GIMR	2022-12-07	FL	R2	ESR1	Fusion, ESR1-YAP1 fusion, ESR1-PCDH11X fusion	Breast cancer	Tamoxifen; Letrozole; Fulvestrant	Preclinical study. ESR1 gene fusions (e.g., ESR1-e6>YAP1 and ESR1-e6>PCDH11X) confer estrogen-independent growth, anti-estrogen resistance, and metastatic progression in ER-positive breast cancer, although remaining sensitive to CDK4/6 inhibitors.	30089255
GIMR	2022-10-07	FL	R2	ESR1	Oncogenic mutations	Breast cancer	Letrozole + Palbociclib; Anastrozole + Palbociclib; Exemestane + Palbociclib	Phase 3. PADA-1. NCT03079011. Median PFS from randomisation was significantly longer in patients switching to Fulvestrant + Palbociclib from Aromatase Inhibitor + Palbociclib (11.9 vs 5.7 months) in patients after detection of rising ESR1 resistance mutation in the circulating tumour DNA assay.	36183733
GIMR	2021-12-22	FL	R2	ESR1	Protein expression	Breast cancer	Entinostat + Exemestane	Phase 3 E2112 trial. NCT02115282. N=608. Entinostat did not improve PFS over placebo (3.3 versus 3.1 months) or OS (23.4 vs 21.7 months) in combination with exemestane. ORR was 6% (Placebo 6%). 35% in the received CDK4/6 prior inhibitor, and 31% received fulvestrant. The Phase 3 data thus contrasts earlier Phase 2 data where a significance improvement of PFS was observed (median PFS 4.3 months versus 2.3 months). 	34357781, 23650416
GIMR	2021-06-15	FL	R2	ESR1	Protein expression	Breast cancer	Venetoclax + Fulvestrant	Phase 2 VERONICA. N=103. ER-positive, HER2-negative locally advanced or metastatic breast cancer treated with prior CDK4/6i. CBR at 24 weeks: 12 (Venetoclax + Fulvestrant) vs 14% (Fulvestrant alone). ORR 4%.	10.1200/JCO.2021.39.15_suppl.1004
GIMR	2025-04-23	FL	R2	ESR1+MDM2	ESR1:Protein expression AND MDM2:Amplification	Breast cancer	Abemaciclib; Palbociclib; Ribociclib	Preclinical study. In metastatic hormone receptor-positive breast cancer, TP53 loss and MDM2 amplification were associated with lack of long-term disease control . CDK2 inhibition overcomes p53 loss, leading to geroconversion and senescence.	39532066
GIMR	2021-10-29	FL	R2	ESR1+PIK3CA	ESR1:protein expression and PIK3CA:oncogenic mutation	Breast cancer	Capivasertib + Paclitaxel	Randomized phase 2 study. BEECH. In the PIK3CA+ sub-population, no difference between was found PFS (capivasertib vs placebo: 10.9 v 10.8 months)	30860570
GIMR	2025-04-23	FL	R2	ESR1+TP53	ESR1:Protein expression AND TP53:Oncogenic mutations	Breast cancer	Abemaciclib; Palbociclib; Ribociclib	Preclinical study. In metastatic hormone receptor-positive breast cancer, TP53 loss and MDM2 amplification were associated with lack of long-term disease control . CDK2 inhibition overcomes p53 loss, leading to geroconversion and senescence.	39532066
GIMR	2025-08-18	FL/NZ	R2	EZH2	Y646C, Y646F, Y646H, Y646N, Y646S, A682G, A682V, A692V	Solid tumours; Atypical teratoid rhabdoid tumour; Malignant rhabdoid tumor; Ewing sarcoma; Epithelioid sarcoma; Histiocytosis; Renal medullary carcinoma; Hepatocellular carcinoma; Ependymoma; Chordoma; Peripheral T-cell lymphoma	Tazemetostat	Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%)	37228094
GIMR	2025-06-09	FL	R2	EZH2	Y666N	Epithelioid sarcoma; Atypical teratoid rhabdoid tumor	Tazemetostat	Preclinical study. Identified molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors, and developed a combination strategy using AURKB targeting to circumvent resistance.	38315003
GIMR	2021-03-16	FL	R2	FANCD2	Oncogenic mutations, Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Olaparib	Two Phase 2 studies. N=46. Olaparib monotherapy showed limited antitumor activity in patients with pancreatic cancer with DDR-GAs, with a median PFS of 5.7 months and median OS of 13.6 months, suggesting a potential therapeutic opportunity for a subset of patients with PDAC harbouring DDR genetic alterations.	33662100
POTTR	2020-04-16	FL	R2	FAT1	Loss-of-function mutations	Solid tumours	Palbociclib; Ribociclib; Abemaciclib	Preclinical study. Loss-of-function mutations in FAT1 led to increased CDK6 expression, and suppressing CDK6 restored sensitivity to CDK4/6i. The induction of CDK6 was mediated by the Hippo pathway, with YAP and TAZ transcription factors accumulating on the CDK6 promoter. Alterations in other Hippo pathway components also contributed to CDK4/6i resistance.	30537512
GIMR	2020-12-03	FL	R2	FBXW7	Deletion	Non-small cell lung cancer	Gefitinib	Preclinical study. Loss of FBXW7 in NSCLC leads to decreased OS and promotes tumor progression, epithelial-mesenchymal transition, migration, and invasion. Deletion of FBXW7 occurs in a significant proportion of lung adenocarcinomas and squamous cell carcinomas. 	29633504
GIMR	2020-12-03	FL	R2	FBXW7	Loss-of-function mutations, R505	Melanoma	Pembrolizumab	Preclinical studies. Inactivation of Fbxw7 impairs dsRNA sensing and confers resistance to PD-1 blockade through downregulation of viral sensing pathways, including decreased expression of MDA5 and RIG1, and diminished type I IFN and MHC-I expression.	32371478
GIMR	2025-06-30	FL	R2	FBXW7	Oncogenic mutation	Solid tumours; Leiomyosarcoma 	Berzosertib	Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit.	39453756
GIMR	2022-02-21	FL	R2	FBXW7	Oncogenic mutations, S668fs*39, L403fs*34, R505C, R505H, R465C, R479Q, G579W, R658Q 	Colorectal adenocarcinoma	Regorafenib	Cell line study. CRC cells with FBXW7 mutation has reduced Mcl-1 degradation and regorafenib resistance.	27399335
GIMR	2020-11-10	FL	R2	FGFR1	Alteration	Lung squamous cell carcinoma	AZD4547	Phase 2 Lung-MAP S1400D substudy. AZD4547 targeting FGFR alteration showed minimal activity with ORR (1/27) 7% and median PFS of 2.7 months in previously treated FGFR-altered squamous NSCLC.	31195180, 33125909
GIMR	2020-04-15	FL	R2	FGFR1	Amplification	Breast cancer	Fulvestrant + Palbociclib; Fulvestrant + Ribociclib	FGFR1 amplification mediates endocrine resistance in ER+ breast cancer by conferring broad resistance to ER, PI3K, and CDK4/6 inhibitors, but retains sensitivity to mTOR inhibitors, suggesting a potential therapeutic role for mTOR inhibitors in ER+/FGFR1+ MBC.	31371343, 30914635
GIMR	2023-12-27	FL	R2	FGFR1	Amplification	Breast cancer	Tamoxifen	Amplification was determined by CISH, if >50% of cells harbored either >5 copies.	20179196
GIMR	2023-02-05	FL	R2	FGFR1	Amplification	Colorectal cancer	PD173074	Retrospective exploratory and cell line studies. In 764 surgically resected colorectal cancers, FGFR1 amplification was found in 3-7 of CRCs. FGFR1 amplification was mutually exclusive with BRAF mutation, microsatellite instability, and MLH1 methylation, and associated with inferior progression-free survival. PD173074 repressed the proliferation of a CRC cell line overexpressing FGFR1 but not cells with FGFR1 amplification.	31096734
GIMR	2022-08-07	FL	R2	FGFR1	Amplification	Lung adenocarcinoma; Medullary thyroid cancer	Selpercatinib	Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers.	35304457
GIMR	2020-06-11	FL	R2	FGFR1	Amplification	Lung squamous cell carcinoma	AZD4547	Phase 2 Lung-MAP S1400D substudy. AZD4547 targeting FGFR alteration showed minimal activity with ORR (1/27) 7% and median PFS of 2.7 months in previously treated FGFR-altered squamous NSCLC.	31195180
GIMR	2024-04-13	FL	R2	FGFR1	Amplification	Solid tumour except urothelial carcinoma	Erdafitinib	Phase 2 NCI-MATCH. EAY131-K1 trial. NCT03167159. N=35. Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications.	38603651
GIMR	2020-06-11	FL	R2	FGFR1	Amplification	Solid tumours	AZD4547	Phase 2 NCI-MATCH trial. AZD4547 showed limited activity in tumors with FGFR aberrations, with confirmed partial responses in 8% of patients, primarily in those with FGFR1-3 point mutations or fusions.	32463741
GIMR	2020-06-11	FL	R2	FGFR1	Amplification, Oncogenic mutations	Solid tumours	AZD4547	Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.	32463741, 10.1200/JCO.2018.36.15_suppl.2503
GIMR	2024-04-13	FL	R2	FGFR1	Amplification; Oncogenic mutations	Breast cancer	Sunitinib	NCT02693535. TAPUR. Phase 2. Single agent Sunitinib had ORR of 7% in FGFR1 altered group. DCR was 27% did not meet the prespecified threshold.	38354330
GIMR	2024-07-19	FL	R2	FGFR1	N546K, N546D	Breast cancer; Endometrial cancer; Solitary fibrous tumour	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. De novo primary resistance mutations prior to Pemigatinib without response	38710951
GIMR	2020-05-22	FL	R2	FGFR1	N564K	Solid tumours	Ponatinib; Dovitinib; Infigratinib	Preclinical study. Biophysical characterization of drug-resistant mutants of fibroblast growth factor receptor 1 (FGFR1) showed that N546K and V561M mutants had varying affinities for different ATP-competitive inhibitors, with V561M mutant showing reduced affinity for PD173074 and N546K showing increased affinity for AMP-PNP.	27558949
GIMR	2024-07-19	FL	R2	FGFR1	V559L, V559M, N546K	Pancreatic adenocarcinoma	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2020-05-22	FL	R2	FGFR1	V561M	Solid tumours	Infigratinib; AZD4547; Zoligratinib	Preclinical study. Resistance to FGFR inhibitors in FGFR1-driven leukemia/lymphomas is associated with either an activating V561M Gatekeeper mutation in the FGFR1 kinase domain or PTEN inactivation. Combined inhibition of FGFR and PI3K pathways shows additive effect in overcoming resistance.	28646488
GIMR	2020-04-15	FL	R2	FGFR2	Amplification	Breast cancer	Fulvestrant + Ribociclib	Preclinical study. FGFR1 amplification/alteration identified as a resistance mechanism to CDK4/6 inhibitors in ER+ breast cancer, with FGFR tyrosine kinase inhibitors (TKIs) abrogating this resistance and potentially improving treatment outcomes.	30914635
GIMR	2024-04-13	FL	R2	FGFR2	Amplification	Solid tumour except urothelial carcinoma	Erdafitinib	Phase 2 NCI-MATCH. EAY131-K1 trial. NCT03167159. N=35. Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications.	38603651
GIMR	2020-06-11	FL	R2	FGFR2	Amplification	Solid tumours	AZD4547	Phase 2 NCI-MATCH trial. AZD4547 showed limited activity in tumors with FGFR aberrations, with confirmed partial responses in 8% of patients, primarily in those with FGFR1-3 point mutations or fusions.	32463741
GIMR	2024-04-13	FL	R2	FGFR2	Amplification; Oncogenic mutations	Breast cancer	Sunitinib	NCT02693535. TAPUR. Phase 2. Single agent Sunitinib had DCR of 0% in FGFR2 altered group.	38354330
GIMR	2025-01-09	FL	R2	FGFR2	BCR-FGFR2 fusion AND V565F	Cholangiocarcinoma	Pemigatinib; Futibatinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2025-01-09	FL	R2	FGFR2	BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N549K (N550K)	Cholangiocarcinoma	Pemigatinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2020-11-03	FL	R2	FGFR2	E565A, L617M	Cholangiocarcinoma	Infigratinib	Preclinical study. FGFR2 kinase domain E565A and L617M are potential drivers of acquired resistance to infigratinib in FGFR2-fusion cholangiocarcinoma.	31911531
GIMR	2024-07-19	FL	R2	FGFR2	E565A, N549K 	Cancer of unknown primary	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2023-06-23	FL	R2	FGFR2	Fusions, FGFR2-CCDC6 fusion, FGFR2-KIAA1598 fusion, FGFR2-TACC2 fusion	Non-small cell lung cancer	Osimertinib; Gefitinib	FGFR2/3 fusions were identified as an acquired resistance mechanism in lung adenocarcinoma following EGFR TKI treatment. Combination of EGFR TKIs and FGFR TKIs showing clinical benefit.	35566609
GIMR	2025-01-09	FL	R2	FGFR2	K642I	Cholangiocarcinoma	Pemigatinib; Infigratinib; Erdafitinib; Zoligratinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2025-01-09	FL	R2	FGFR2	K660N	Cholangiocarcinoma	Infigratinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-09-28	FL	R2	FGFR2	L618F	Cholangiocarcinoma	Zoligratinib	Preclinical and clinical study. FGFR2 extracellular domain in-frame deletions (EID) in intrahepatic cholangiocarcinoma are present in 2.8% of patients, conferring initial sensitivity to FGFR inhibitors. The L618F FGFR2 kinase domain mutation leads to acquired resistance, which can be overcome by futibatinib.	33926920
GIMR	2023-01-23	FL	R2	FGFR2	N549D (N550D), N549K (N550K), V563I, V565I, V565L, E566A, E566G, K642I, L642R, K660M	Cholangiocarcinoma	Infigratinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2023-01-23	FL	R2	FGFR2	N549D (N550D), N549K (N550K), V565I, V565L, K642I, K660M	Cholangiocarcinoma	Pemigatinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2025-01-09	FL	R2	FGFR2	N549H (N550H), N549K (N550K), E566A, E566G, L618M, L618V	Cholangiocarcinoma	Pemigatinib; Infigratinib; Erdafitinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2022-07-27	FL	R2	FGFR2	N549H (N550H), V565I, V565L, E566G, K660M	Solid tumours	AZD4547; Infigratinib	In cell line studies, futibatinib is active several drug-resistant FGFR2 mutants including V565I gatekeeper mutants.	32973082
GIMR	2023-02-22	FL	R2	FGFR2	N549K	Cholangiocarcinoma	AZD4547; Infigratinib; Erdafitinib; Pemigatinib		34272467
GIMR	2023-02-22	FL	R2	FGFR2	N549K	Cholangiocarcinoma	AZD4547; Infigratinib; Pemigatinib		34272467
GIMR	2025-01-09	FL	R2	FGFR2	N549K (N550K), N549D (N550D), K660M	Cholangiocarcinoma	Pemigatinib;Infigratinib; Erdafitinib; E7090; Zoligratinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2024-07-19	FL	R2	FGFR2	N549K (N550K), N549D (N550D), N549H (N550H), N549F, M537I, V564I, V564F, V564L, L617V, K641R, K569M	Cholangiocarcinoma	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2021-07-06	FL	R2	FGFR2	N549K (N550K), N549H (N550H), E565A, L617V, K641R, K659M	Cholangiocarcinoma	Pemigatinib	Exploratory analysis of on-target secondary mutations from FIGHT-202 trial. No gatekeepter V564 mutations were identified.	33218975
GIMR	2023-01-23	FL	R2	FGFR2	N549K (N550K), V565L, K642I, K660M	Cholangiocarcinoma	Erdafitinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2024-07-19	FL	R2	FGFR2	N549K, V395D, R664W, K505E	Breast cancer; Endometrial cancer; Solitary fibrous tumour	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. De novo primary resistance mutations prior to Pemigatinib without response	38710951
GIMR	2023-02-22	FL	R2	FGFR2	N549S, N549H (N550H)	Cholangiocarcinoma	Dovitinib	Preclinical study. Comprehensive functional evaluation of 160 nonsynonymous FGFR mutations and ten fusion genes revealed varying transforming activity and sensitivity to seven FGFR TKIs, with several hotspot mutants showing relative resistance, and compound mutations affecting TKI-sensitivity.	34272467
GIMR	2025-01-09	FL	R2	FGFR2	N550, L552F, V565, E566A, L618V, N653S	Cholangiocarcinoma	Futibatinib	Phase 1/2 FOENIX study. N=300. Futibatinib biomarker analysis detected treatment-emergent kinase mutation variants within 6 weeks of radiologic progression. CDKN2B alteration associated with reduced PFS in cholangiocarcinoma.	39672383
GIMR	2020-11-03	FL	R2	FGFR2	N550, V565, E565A, C492	Cholangiocarcinoma	Futibatinib		10.1016/S0959-8049(20)31121-7
GIMR	2020-06-11	FL	R2	FGFR2	Oncogenic mutations and NOT Amplification	Solid tumours	AZD4547	Phase 2 NCI-MATCH trial (arm W). Patients with tumors harboring FGFR aberrations treated with AZD4547 showed confirmed partial responses in 8% of patients, limited to those with FGFR1-3 point mutations or fusions, with a higher response rate of 22% in patients with FGFR fusions.	10.1200/JCO.2018.36.15_suppl.2503
GIMR	2025-01-09	FL	R2	FGFR2	V563L, E566A, E566G, K642R	Cholangiocarcinoma	Infigratinib; Zoligratinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2024-07-19	FL	R2	FGFR2	V564F	Gastric cancer	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2023-02-22	FL	R2	FGFR2	V564F, N549H (N550H), N549K (N550K), E565A, L617V, K641R, K659M	Cholangiocarcinoma	Infigratinib	Preclinical study and case series. Polyclonal secondary FGFR2 mutations in the kinase domain were identified in cfDNA and biopsies of FGFR2 fusion-positive cholangiocarcinoma patients, driving acquired resistance to FGFR inhibitor BGJ398, and were surmountable by distinct FGFR inhibitors.	28034880
GIMR	2024-09-25	FL	R2	FGFR2	V564F, V564L	Cholangiocarcinoma	Futibatinib		37270847
GIMR	2024-09-25	FL	R2	FGFR2	V564F, V564L, N549D (N550D), N549H (N550H), N549K (N550K), E565A, V564I, L617V	Cholangiocarcinoma	Infigratinib		37270847
GIMR	2024-09-25	FL	R2	FGFR2	V564F, V564L, N549D (N550D), N549K (N550K), E565A, L617V	Cholangiocarcinoma	Pemigatinib		37270847
GIMR	2024-09-25	FL	R2	FGFR2	V564F, V564L, N549K (N550K), N549D (N550D)	Cholangiocarcinoma	Erdafitinib		37270847
GIMR	2025-01-09	FL	R2	FGFR2	V565I	Cholangiocarcinoma	Pemigatinib; Derazantinib; Zoligratinib; AZD4547; Futibatinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2020-05-22	FL	R2	FGFR2	V565I, N549K (N550K), V564M, V564F	Solid tumours	Infigratinib; AZD4547; Zoligratinib; Dovitinib; Ponatinib	Gatekeeper mutation	26224133, 23908597
GIMR	2023-01-23	FL	R2	FGFR2	V565L	Cholangiocarcinoma	Futibatinib	FOENIX-CCA2. NCT02052778. Cell line sensitivity data from mutational screening with Ba/F3 cells.	36652354
GIMR	2025-01-09	FL	R2	FGFR2	V565L	Cholangiocarcinoma	Pemigatinib; Derazantinib; Zoligratinib; AZD4547; Futibatinib; Erdafitinib	Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified.	39706336
GIMR	2024-04-13	FL	R2	FGFR3	Amplification	Solid tumour except urothelial carcinoma	Erdafitinib	Phase 2 NCI-MATCH. EAY131-K1 trial. NCT03167159. N=35. Erdafitinib did not meet its primary end point of efficacy as determined by ORR in treatment-refractory solid tumors harboring FGFR1-4 amplifications.	38603651
GIMR	2020-06-11	FL	R2	FGFR3	Amplification, Fusion, S249C	Lung squamous cell carcinoma	AZD4547	Phase 2 Lung-MAP S1400D substudy. AZD4547 targeting FGFR alteration showed minimal activity with ORR (1/27) 7% and median PFS of 2.7 months in previously treated FGFR-altered squamous NSCLC.	31195180, 33125909
GIMR	2023-06-23	FL	R2	FGFR3	FGFR3-TACC3 fusion	Non-small cell lung cancer	Osimertinib; Gefitinib	Retrospective observational study. FGFR2/3 fusions, particularly FGFR3-TACC3, were identified as a rare acquired resistance mechanism in advanced NSCLC patients treated with EGFR TKIs, and combining EGFR TKIs with FGFR TKIs showed clinical benefit in patients with FGFR3-TACC3 fusions.	35566609
GIMR	2021-06-25	FL	R2	FGFR3	FGFR3-TACC3 fusion	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2020-06-10	FL	R2	FGFR3	Fusion	Non-small cell lung cancer	Osimertinib	Retrospective observational study. Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy revealed various mechanisms of resistance, with EGFR T790M mutation being the most common (63%), followed by MET amplification (5%), HER2 amplification (13%), and small cell transformation (3%), also including small number of off-target mechanism such as FGFR3 fusion.	23470965
GIMR	2023-02-22	FL	R2	FGFR3	N540K, V555M, L608V	Cholangiocarcinoma	Infigratinib; AZD4547; Zoligratinib	Preclinical study and case series. Polyclonal secondary FGFR2 mutations in the kinase domain were identified in cfDNA and biopsies of FGFR2 fusion-positive cholangiocarcinoma patients, driving acquired resistance to FGFR inhibitor BGJ398, and were surmountable by distinct FGFR inhibitors.	28034880
GIMR	2020-05-22	FL	R2	FGFR3	V443, V555M	Solid tumours	Infigratinib; AZD4547; Zoligratinib	Phase 1/2 trial. BGJ398. N = 67. Patients with metastatic urothelial carcinoma bearing FGFR3 alterations. Overall response rate of 25.4% and disease control rate of 64.2% observed. Preclinical study identified gatekeeper mutation (FGFR3(V555M)) in FGFR3 as a mechanism of acquired resistance to FGFR inhibitors.	22869148, 29848605
GIMR	2025-02-06	FL	R2	FGFR3	V553M, V555L, V555M, M528I, N540S, N540K	Urothelial carcinoma	Pemigatinib	Phase 2. FIGHT-201. NCT02872714. N=260. Secondary acquired on-target resistance mutations detected at end of treatment in 6 patients.	37956738
GIMR	2024-07-19	FL	R2	FGFR3	V555M, V555L	Non-small cell lung cancer	Pemigatinib	Phase2 FIGHT-207 basket trial. NCT03822117. Pemigatinib showed ORR of 26.5% and 9.4% in patients with FGFR fusions/rearrangements and activating non-kinase domain mutations respectively, with TP53 co-mutations associated with lack of response and BAP1 alterations with higher response rates, while FGFR1-FGFR3 gatekeeper and molecular brake mutations led to acquired resistance.	38710951
GIMR	2020-05-22	FL	R2	FGFR4	V550E, V550L	Solid tumours; Hepatocellular carcinoma	Fisogatinib	Preclinical and clinical study. On-target FGFR4 kinase domain mutations were identified as a mechanism of acquired resistance to fisogatinib in HCC patients with aberrant FGF19 expression, validating FGFR4 as an oncogenic driver.	31575540
GIMR	2022-10-16	FL	R2	FLT3	Amplification	Colorectal adenocarcinoma	Sunitinib	Phase 2 TAPUR basket study. NCT02693535. Sunitinib showed no clinical activity in patients with metastatic colorectal cancer with FLT-3 amplification, as no objective responses were observed (ORR 0%) and only two patients had stable disease at 16 weeks, suggesting FLT-3 amplification may not be a sufficient target for sunitinib.	33068284
GIMR	2020-04-16	FL	R2	FLT3	D835	Acute myeloid leukaemia	Sorafenib	Clinical study. Relapsed or refractory FLT3-ITD(+) AML patients treated with sorafenib showed initial response but subsequent resistance was associated with the emergence of D835 mutation in leukemia initiating cells, suggesting selection of more aggressive subclones carrying both FLT3-ITD and D835 mutations.	22368270
GIMR	2024-10-05	FL	R2	FLT3	F691L	Acute myeloid leukaemia	Gilteritinib	Secondary FLT3-F691L gatekeeper mutations or BCR-ABL1 fusions were identified at progression to Gilteritinib.	31088841
GIMR	2025-06-21	FL	R2	FLT3	F691L	Acute myeloid leukaemia	Gilteritinib	Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations.	38231480
GIMR	2025-06-21	FL	R2	FLT3	F691L, D835Y, D835V, Y842C	Acute myeloid leukaemia	Quizartinib	Preclinical study. Foretinib overcomes secondary FLT3 mutations, including F691L, D835Y/D835V, and Y842C, that confer resistance to quizartinib and gilteritinib with potent antileukemia activity in AML cells and primary blasts harboring FLT3-ITD mutations.	38231480
MoSTLLy	2023-01-12	XT	R2	FLT3	Internal tandem duplication	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
GIMR	2021-10-06	FL	R2	FLT3	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
SuboKB	2020-04-16	ST	R2	GLI1	Overexpression	Basal cell carcinoma	Vismodegib	Preclinical study. Genomic analysis of basal cell carcinoma revealed that Smoothened (SMO) inhibitor resistance is associated with Hedgehog pathway reactivation through SMO mutations that impair drug binding, and copy number changes in SUFU and GLI2.	25759019
SuboKB	2020-04-16	ST	R2	GLI2	Overexpression	Basal cell carcinoma	Vismodegib	Preclinical studies. Genomic analysis of basal cell carcinoma tumors and a medulloblastoma patient treated with vismodegib revealed that acquired resistance to Smoothened antagonists occurs through Hedgehog pathway reactivation via SMO mutations that either impair drug binding or constitutively activate SMO.	21771911, 25759019
GIMR	2023-04-19	FL	R2	GNA11	Oncogenic mutations; Q209L	Solid tumour except Uveal melanoma	Trametinib	Phase 2. NCI-MATCH. NCT02465060. EAY131. In GNA11/GNAQ cohort, 1 of 4 responder was seen (melanoma). Overall, however, trametinib did not demonstrate meaningful clinical activity.	37053535
GIMR	2023-04-19	FL	R2	GNAQ	Oncogenic mutations	Solid tumour except Uveal melanoma	Trametinib	Phase 2. NCI-MATCH. NCT02465060. EAY131. In GNA11/GNAQ cohort, 1 of 4 responder was seen (melanoma). Overall, however, trametinib did not demonstrate meaningful clinical activity.	37053535
GIMR	2026-03-05	FL	R2	GNAS	K216N	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2023-12-14	FL/BZ	R2	GNAS	R201C, R201H	Non-small cell lung cancer	Osimertinib	Case report. A NSCLC patient with osimertinib resistance harboring GNAS R201C and R201H mutations showed stable disease after treatment with trametinib, suggesting GNAS R201 mutations confer osimertinib resistance and trametinib as a potential treatment option.	35946511
GIMR	2020-05-15	FL	R2	HGF	Overexpression	Gastric cancer	MEK inhibitor	Preclinical study. Overexpression of HGF induces resistance to c-MET tyrosine kinase inhibitors in gastric cancer cells through an autocrine manner, despite c-MET TKIs inhibiting downstream signaling and cell proliferation.	28314274
GIMR	2022-01-28	FL	R2	HLA-A	A*03	Solid tumours	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody; Anti-CTLA-4 monoclonal antibody; Avelumab; Nivolumab; Avelumab + Axitinib	HLA-A*03 was significantly associated with reduced OS after immune checkpoint inhibitor in the MSK-IMPACT and DFCI studies, JAVELIN solid tumour trials (HR 1.22-1.48), reduced PFS in nivolumab trials (CheckMate 009, 010, 025, HR1.31) and in JAVELIN renal 101 (HR 1.59 per allele) but not the control group. The meta-analysis showed that HLA-A*03 was associated with poor outcomes treated with ICI at genome-wide significance.	34895481
GIMR	2024-02-26	FL	R2	HRAS	G12C	Solid tumour	Adagrasib; GDC6036	Preclinical study. Both adagrasib and GDC6036 are KRAS G12C specific inhibitors.	38236605
GIMR	2020-07-02	FL	R2	HRAS	G12V	Solid tumours	Sonidegib; Vismodegib	Preclinical study. RAS/MAPK pathway activation drives off-target mechanism of resistance to Smo inhibition, with Sufu mutations maintaining Shh pathway activity and emerging RAS/MAPK activation in Smo inhibitor-treated BCC patients.	26130651
GIMR	2022-08-10	FL	R2	HRAS	G13D	Colorectal adenocarcinoma	Panitumumab; Cetuximab; Cetuximab + Irinotecan; Cetuximab + FOLFIRI; FOLFOX + Panitumumab	Case report and cell line study. A single case report of metastatic colorectal cancer harbouring HRAS G13D mutation, showing lack of response to Panitumumab. HRAS mutations constitute 1% of colorectal cancer.	26561417
GIMR	2023-12-09	FL	R2	HRAS	G13V	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2026-03-05	FL	R2	HRAS	G13V	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2023-11-05	FL	R2	HRAS	Oncogenic mutation; Q61R	Salivary gland cancers; Salivary duct carcinoma; Epithelial-myoepithelial carcinoma	Tipifarnib	Phase 2. NCT02459813. N=13. Tipifarnib demonstrated a modest clinical activity in HRAS-mutant, R/M SGC with a DCR of 58%. One objective response was observed. 7 patients had SD as their best response. The median PFSwas 7 months. the median OS was 18 months.	32557577
GIMR	2021-06-06	FL	R2	HRAS	Oncogenic mutations	Solid tumours	Selumetinib	Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed.	10.1200/JCO.2021.39.15_suppl.10008
GIMR	2023-08-23	FL	R2	IDH1	D279N	Cholangiocarcinoma	Ivosidenib	Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib is related to the treatment-emergent D279N mutation, where the double mutant showed impaired binding to ivosidenib despite reduced efficiency in producing 2HG.	36056177
GIMR	2026-02-02	FL	R2	IDH1	Oncogenic mutations	Chondrosarcoma; Solid tumours	Olaparib	Phase 2 study. NCT03212274. N=26. Olaparib did not demonstrate activity in IDH-mutant chondrosarcomas and other solid tumors with ORR 0%, median PFS of 2 months, and median OS of 7.5 months.	10.1200/JCO.2025.43.16_suppl.3087
GIMR	2025-06-09	FL	R2	IDH1	R132	Acute myeloid leukaemia	BAY1436032	Phase 1 study. NCT03127735. N=27. BAY1436032, an IDH1 inhibitor, showed modest clinical activity in IDH1-mutant AML with an overall response rate of 15% (4/27; 1 CRp, 1 PR, 2 MLFS) and median treatment duration of 6 months among responders.	32733012
GIMR	2025-06-09	FL	R2	IDH1	R132	Glioblastoma; Intrahepatic cholangiocarcinoma; Solid tumours except Low-grade glioma	BAY1436032	Phase I trial. NCT02746081. BAY1436032 showed clinical activity in a subset of heavily pretreated subjects with lower grade glioma (LGG), with an ORR of 11% and SD in 43%, and a 3-month PFS rate of 0.31, while no objective responses were observed in glioblastoma, intrahepatic cholangiocarcinoma, or other tumor types.	33622704
GIMR	2021-03-19	FL	R2	IDH1	R132C, R132	Cholangiocarcinoma	Olaparib	Phase 2 Basket trial. Olaparib for IDH mutations. No responders in four cholangiocarcinoma cases (3 cases with R132C).	10.1200/PO.20.00247
GIMR	2023-03-08	FL	R2	IDH1	R132C, R132	Cholangiocarcinoma	Olaparib	OLAPCO. No responses were seen in Cholangiocarcinoma harbouring IDH1/2 mutations treated with Olaparib	34994649
GIMR	2021-10-06	FL	R2	IDH1	S280F	Acute myeloid leukaemia	Ivosidenib	Sequencing of progression sample revealed S280F at dimer interface resulting in steric hinderence of drug binding in structural modelling, restoring 2HG production.	33832922
GIMR	2021-10-06	FL	R2	IDH1	S280F	Acute myeloid leukaemia	Ivosidenib	Phase 1 trial. NCT02074839. N=174. Multiple mechanisms of resistance to ivosidenib were identified in IDH1-mutant relapsed/refractory AML, including RTK pathway mutations associated with primary resistance, and second-site IDH1 mutations and IDH2 mutations restoring 2-HG production associated with acquired resistance.	32380538
MoSTLLy	2023-01-12	XT	R2	IDH1	S280F, R119P, G131A, D279N, G289D, H315D	Acute myeloid leukaemia	Ivosidenib	2-HG restoration as a result of mutations preventing drug/cofactor binding and/or emergence of an IDH2 mutation represents a mechanism of secondary resistance	32380538
GIMR	2026-02-02	FL	R2	IDH2	Oncogenic mutations	Chondrosarcoma; Solid tumours	Olaparib	Phase 2 study. NCT03212274. N=26. Olaparib did not demonstrate activity in IDH-mutant chondrosarcomas and other solid tumors with ORR 0%, median PFS of 2 months, and median OS of 7.5 months.	10.1200/JCO.2025.43.16_suppl.3087
MoSTLLy	2023-01-12	XT	R2	IDH2	R140Q, R172K	Acute myeloid leukaemia	Ivosidenib	2-HG restoration as a result of mutations preventing drug/cofactor binding and/or emergence of an IDH2 mutation represents a mechanism of secondary resistance	32380538
GIMR	2023-08-23	FL	R2	IDH2	R172K	Cholangiocarcinoma	Ivosidenib	Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib is related to the treatment-emergent IDH2 R172 mutation.	36056177
GIMR	2023-03-08	FL	R2	IDH2	R172K, R172	Cholangiocarcinoma	Olaparib	OLAPCO. No responses were seen in Cholangiocarcinoma harbouring IDH1/2 mutations treated with Olaparib	34994649
GIMR	2021-03-31	FL	R2	Intrinsic subtype	Basal-like	Breast cancer	Ribociclib + Tamoxifen; Ribociclib + Fulvestrant; Ribociclib + Letrozole; Ribociclib + Anastrozole	Exploratory analysis from MONALEESA-7, -3, 2 using intrinsic subtype 152 gene expression panel for classification into PAM50-subtypes. No difference in ORR was seen in basal-like molecular subtype (Ribociclib 25 vs Placebo 29%, NS). No difference in was seen in mPFS.	33769862
GIMR	2022-04-13	FL	R2	IRS2+BRAF	IRS2:Amplification AND BRAF:V600E	Colorectal adenocarcinoma	BMS-754807	Cell lines with BRAF V600E or KRAS G13D mutation were resistant to IGF1R inhibition BMS-754807	25527633
GIMR	2022-04-13	FL	R2	IRS2+KRAS	IRS2:Amplification AND KRAS:G13D	Colorectal adenocarcinoma	BMS-754807	Cell lines with BRAF V600E or KRAS G13D mutation were resistant to IGF1R inhibition by BMS-754807	25527633
GIMR	2022-05-17	FL	R2	JAK1	F958V, F958C, P960	Liquid cancers	Ruxolitinib	Preclinical study. Cell line study identified JAK1 and JAK2-activating mutations, specifically those targeting F958 and P960 in JAK1 and Y931 in JAK2, confer resistance to ATP-competitive JAK inhibitors.	21393331
GIMR	2022-09-02	FL	R2	JAK1	Loss-of-function mutations, deletion	Melanoma	Pembrolizumab	Case series. Acquired JAK1/JAK2 loss-of-function mutations resulted in lack of response to IFN-gamma.	27433843
GIMR	2022-09-02	FL	R2	JAK2	Loss-of-function mutations, deletion	Melanoma	Pembrolizumab	Case series. Acquired JAK1/JAK2 loss-of-function mutations resulted in lack of response to IFN-gamma.	27433843
GIMR	2022-05-17	FL	R2	JAK2	Y931C, Y931C and V617F	Liquid cancers	Ruxolitinib	Preclinical study. Cell line study identified JAK1 and JAK2-activating mutations, specifically those targeting F958 and P960 in JAK1 and Y931 in JAK2, confer resistance to ATP-competitive JAK inhibitors.	21393331
GIMR	2025-07-07	FL	R2	KIT	A502_Y503dup, K642E, V654A, T670I, D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P	Gastrointestinal stromal tumour	Imatinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	R2	KIT	A502_Y503dup, K642E, V654A, T670I, D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P	Gastrointestinal stromal tumour	Regorafenib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	R2	KIT	A502_Y503dup, K642E, V654A, T670I, D816A, N822K, A502_Y503dup and N822K, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P	Gastrointestinal stromal tumour	Bezuclastinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2020-05-15	FL	R2	KIT	A502_Y503dup, V560D, K642E, T670I, T670A, T670V	Gastrointestinal stromal tumour	Avapritinib	Primary GIST resistance	19164557,31085175,30792533,31123346,30101284, 31270078
GIMR	2020-05-15	FL	R2	KIT	A502_Y503dup, V560D, T670I, D816F, D816V, D816, D820A	Gastrointestinal stromal tumour	Imatinib	Primary GIST resistance	12901973, 19164557,31085175,30792533,31123346,30101284, 31270078
GIMR	2020-05-15	FL	R2	KIT	A829P, T670I	Melanoma	Imatinib	Preclinical study. Secondary c-Kit mutations (A829P and T670I) confer acquired resistance to RTK inhibitors (imatinib and nilotinib) in c-Kit mutant melanoma cells, but alternative RTK inhibitors (dasatinib and sunitinib) or combined inhibition of MAPK and PI3K pathways may overcome this resistance.	23582185
GIMR	2020-04-23	FL	R2	KIT	Amplification	Melanoma	Imatinib	Phase 2 trial. Imatinib demonstrates efficacy in melanomas with KIT mutations (54% response rate) but shows no response in tumors with KIT amplification only (0% ORR). KIT mutation status serves as a predictor of response, while NRAS mutations and KIT copy number gain are associated with imatinib resistance.	23775962
GIMR	2020-12-31	FL	R2	KIT	Amplification	Melanoma	Nilotinib	Phase 2 UN10-06 trial. Nilotinib in metastatic melanoma with KIT gene aberrations showed durable response in a subset of patients with specific KIT mutations in exons 11 and 17, although the primary endpoint of response rate was not met. In the KIT amplification only subgroup, 1/15 patients responded (ORR 6%) with a duration of response of 5 weeks. Gene co-mutation status was not available.	26424760
GIMR	2025-07-07	FL	R2	KIT	D816A, A502_Y503dup and N822K, V654A and D816A	Gastrointestinal stromal tumour	Nintedanib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	R2	KIT	D816A, D820A, N822K, A829P, A502_Y503dup and N822K, V654A and D816A, V654A and N822K, V654A and A829P	Gastrointestinal stromal tumour	Sunitinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2020-05-15	FL	R2	KIT	D816F, D816G, D816H, D816V, D816	Gastrointestinal stromal tumour	Sorafenib	Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842. (Merged 2025-05-28)	22665524
GIMR	2020-04-23	FL	R2	KIT	D816V	Gastrointestinal stromal tumour	Imatinib; Sunitinib; Regorafenib	Preclinical studies and case reports. Type II c-Kit inhibitors such as BLU-285 inhibit activation loop mutants including KIT D816V and PDGFRA D842V mutations, demonstrating activity in phase 1 studies in patients with KIT/PDGFRA-driven cancers.	29093181
GIMR	2020-06-27	FL	R2	KIT	D816V, D816H, D816	Gastrointestinal stromal tumour	Axitinib	Preclinical study. Axitinib showed potent activity against various cKIT primary and secondary mutations, including imatinib-resistant mutations T670I and V654A, in GIST preclinical models and patient-derived primary cells, but lacked activity in D816.	31205508
GIMR	2025-04-21	FL	R2	KIT	D816V, Y823D	Gastrointestinal stromal tumour	Pazopanib	AccessFDA data. GW786034B: weak activity against V654A mutant (IC50=1.45 uM); inactive against D816V (IC50 >10 uM) and Y823D (IC50 >5 uM) mutations.	https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_PharmR.pdf
GIMR	2024-01-07	FL	R2	KIT	Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation	Gastrointestinal stromal tumour	Ripretinib	Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. Ripretinib showed significantly inferior PFS to Sunitinib (Median PFS 4.0 v 15.0 months) in patients with KIT exon 13/14 co-mutation.	38182785, 10.1200/JCO.2023.41.36_suppl.397784
GIMR	2023-01-25	FL	R2	KIT	Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation	Gastrointestinal stromal tumour	Sunitinib	Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. No response in 25 patients was observed in patients with acquired Exon 13/14 mutations prior imatinib exposure. Median PFS 1.5 months.	38182785, 10.1200/JCO.2023.41.36_suppl.397784
GIMR	2020-12-31	FL	R2	KIT	Exon 13 mutation	Melanoma	Nilotinib	Phase 2 UN10-06 trial. In KIT exon 13 mutation subgroup, 0/15 response. Gene co-mutation status was not available in the case.	26424760
GIMR	2020-05-15	FL	R2	KIT	K642E, D816V, D820A, D816	Gastrointestinal stromal tumour	Sunitinib	Preclinical and biomarker studies. Investigations into KIT mutations and resistance mechanisms revealed that midostaurin and avapritinib exhibit distinct resistance profiles, with T670I gatekeeper mutation conferring avapritinib resistance, and that ripretinib, a switch-control kinase inhibitor, broadly inhibits KIT and PDGFRA mutants, while rapid alternation of sunitinib and regorafenib suppresses growth of polyclonal imatinib-resistant GIST.	19164557, 31085175, 30792533, 31123346, 30101284, 31270078
GIMR	2025-07-07	FL	R2	KIT	K642E, T670I, A502_Y503dup and N822K, V654A and D816A  	Gastrointestinal stromal tumour	Avapritinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2023-06-27	FL	R2	KIT	NOT Oncogenic mutations, V654A, T670I	Gastrointestinal stromal tumour	Bezuclastinib	Phase 1b/2a trial. NCT02401815. In refractory GIST, the combination of Bezuclastinib (type I KIT inhibitor) and sunitinib (type II KIT inhibitor) demonstrated a median PFS of 12.1 months and clinical benefit rate of 80%. KIT wildtype tumors and those harboring V654A or T670I mutations showed lack of sensitivity to this combination therapy.	34236401
GIMR	2021-10-06	FL	R2	KIT	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
GIMR	2020-12-31	FL	R2	KIT	Overexpression	Adenoid cystic carcinoma	Imatinib	Phase 2 consortium-based study. N=15. ORR 0%.	15659505
GIMR	2021-07-01	FL	R2	KIT	Protein expression, Overexpression	Adenoid cystic carcinoma	Imatinib	Phase 2. N=10. In patients with c-Kit advanced adenoid cystic carcinoma of the salivary gland, there was no responder to imatinib. Two patients had stable disease.	16757202
GIMR	2020-05-15	FL	R2	KIT	R796G, C809G, D816F, D816G, D816H, D816V, D816, D820A, D820E, D820G, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N	Gastrointestinal stromal tumour	Sunitinib	Preclinical studies investigated secondary resistance mechanisms in KIT-mutant GIST, identifying distinct resistance profiles for ATP-competitive inhibitors midostaurin and avapritinib, and demonstrating the potential of combining TKIs with complementary activity against resistant mutations to suppress growth of polyclonal imatinib-resistance.	19164557, 22665524, 31085175, 30792533, 31123346, 30101284, 31270078, 10.1200/jco.2013.31.15_suppl.10510
GIMR	2025-07-07	FL	R2	KIT	T670I, V654A and D816A, V654A and D820A	Gastrointestinal stromal tumour	IDRX-42	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	R2	KIT	T670I, V654A and D816A, V654A and D820A, V654A and N822K, V654A and A829P	Gastrointestinal stromal tumour	Ripretinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	R2	KIT	T670I, V654A and D820A, V654A and N822K, V654A and A829P	Gastrointestinal stromal tumour	NB003	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2021-08-13	FL	R2	KIT	V559A, V559D, D816H, D816V	Gastrointestinal stromal tumour	Cabozantinib	Preclinical study. Cabozantinib, a MET and VEGFR2 inhibitor, suppresses metastasis, angiogenesis, and tumor growth by inhibiting MET and VEGFR2 phosphorylation, with potential therapeutic application in cancers with dysregulated MET and VEGFR signaling. Drug sensitivity screen revealed relative insensitivity of KIT V559A, V559D, D816H, D816V to Cabozantinib.	21926191
GIMR	2020-06-18	FL	R2	KIT	V560D, V560D and V654A, V560D and and V670I, T670I, T670V	Solid tumours	Avapritinib	Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation.	31270078
GIMR	2020-05-15	FL	R2	KIT	V654A, D816V, D816	Gastrointestinal stromal tumour	Regorafenib	Preclinical studies. Secondary kinase domain mutations in KIT as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in GIST, with distinct resistance profiles observed for midostaurin and avapritinib, and ripretinib showing broad spectrum inhibition of oncogenic and drug-resistant KIT and PDGFRA variants.	19164557,31085175,30792533,31123346,30101284, 31270078, 10.1200/jco.2013.31.15_suppl.10510
GIMR	2020-06-18	FL	R2	KIT	V654A, N655K, Y627C, D677N, T670I, T670A, T670V	Solid tumours	Midostaurin	Cell line study. Midostaurin and avapritinib, ATP-competitive inhibitors targeting active KIT conformation, exhibit distinct resistance profiles to secondary kinase domain mutations in exon 17-mutant KIT, with avapritinib being selectively vulnerable to the T670I gatekeeper mutation.	31270078
GIMR	2020-05-15	FL	R2	KIT	V654A, N655S, T670I, N680K, F681L, C809G, D816G, D816H, D816V, D816, D820G, D820E, D820N, D820V, D820Y, N822H, N822I, N822K, N822T, N822Y, Y823D, A829P, S840N 	Gastrointestinal stromal tumour	Imatinib	Preclinical studies. Secondary kinase domain mutations in KIT as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in GIST, with distinct resistance profiles observed for midostaurin and avapritinib, and ripretinib showing broad spectrum inhibition of oncogenic and drug-resistant KIT and PDGFRA variants.	19164557,31085175,30792533,31123346,30101284, 31270078
GIMR	2020-05-15	FL	R2	KIT	V654A, N655S, T670I, N822T, S840N	Gastrointestinal stromal tumour	Avapritinib	Preclinical studies. Secondary kinase domain mutations in KIT as a mechanism of resistance to tyrosine kinase inhibitors (TKIs) in GIST, with distinct resistance profiles observed for midostaurin and avapritinib, and ripretinib showing broad spectrum inhibition of oncogenic and drug-resistant KIT and PDGFRA variants.	19164557,31085175,30792533,31123346,30101284, 31270078
GIMR	2022-03-20	FL	R2	KIT	V654A, N822K, N822Y, D820G 	Gastrointestinal stromal tumour	Imatinib + Binimetinib	Phase 2 trial. NCT01991379. Imatinib plus Binimetinib showed a high ORR of 69% in treatment-naive advanced GIST patients, with 29 of 42 evaluable patients achieving confirmed PR, and median PFS of 29.9 months. Emergent secondary KIT mutations and CDKN2A alterations associated with resistance were identified.	35041493
GIMR	2025-06-20	FL	R2	KLHL6	Protein expression	Diffuse large B-cell lymphoma	Polatuzumab vedotin + Bendamustine + Rituximab	Preclinical study. Genome-wide CRISPR-Cas9 screens in DLBCL cell lines revealed that CD79B glycosylation and KLHL6 determine sensitivity to Polatuzumab vedotin (Pola-V) by influencing epitope availability and CD79B protein levels, respectively.	38683128
GIMR	2024-07-19	FL	R2	KRAS	A59T, G13D	Cancer of unknown primary	Pemigatinib	Phase 2 FIGHT-207 basket trial. NCT03822117. Pemigatinib showed ORR of 27% and 9% in cohorts with FGFR fusions/rearrangements and activating non-kinase domain mutations, respectively, with TP53 co-mutations associated with lack of response and BAP1 alterations with higher response rates, and identified FGFR1-FGFR3 gatekeeper and molecular brake mutations as acquired resistance mechanisms. Acquired resistance mutations following Pemigatinib were identified.	38710951
GIMR	2020-11-25	FL	R2	KRAS	Amplification	Colorectal adenocarcinoma	Binimetinib + Encorafenib	Preclinical study and paired pre-post treatment sequencing. Identified alterations in MAPK pathway genes, including KRAS amplification, in resistant BRAF-mutant colorectal cancer tumors post-RAF inhibitor combination treatment.	25673644
GIMR	2026-02-24	FL	R2	KRAS	Amplification	Colorectal adenocarcinoma	Cetuximab	Retrospective analysis. COH cohort and Flatiron cohorts. N=15. Wild-type RAS amplification in mCRC had median TTD 2.5 (COH) and 4.7 (CGDB) months vs 7.6 months in RAS wild-type, similar magnitude to EGFRmAb as RAS mutations. OS 11.4 vs 13.7 months. 	33465286
GIMR	2022-04-19	FL	R2	KRAS	Amplification	Colorectal adenocarcinoma	Cetuximab; Panitumumab	Preclinical study and patient sample analysis. KRAS amplification, detected in 0.67% of 1039 CRC specimens, is associated with primary resistance to EGFR-targeted therapy, with tumors or cell lines harboring this lesion being non-responsive to anti-EGFR inhibitors.	23404247
GIMR	2022-04-19	FL	R2	KRAS	Amplification	Colorectal adenocarcinoma	Cetuximab; Panitumumab	Retrospective study. Multi-institutional cohort showing disease progression on treatment in 8 patients with KRAS amplified CRC receiving anti-EGFR therapies.	32376853
GIMR	2025-12-15	FL	R2	KRAS	Amplification	Colorectal adenocarcinoma	Cetuximab; Panitumumab	Case report	28178681
GIMR	2020-11-25	FL	R2	KRAS	Amplification	Colorectal adenocarcinoma	Dabrafenib + Panitumumab	Preclinical study. Identified alterations in MAPK pathway genes, including KRAS amplification, in paired pretreatment and postprogression tumor biopsies from patients with BRAF-mutant colorectal cancer treated with RAF inhibitor combinations, driving clinical acquired resistance.	25673644
GIMR	2021-01-03	FL	R2	KRAS	Amplification	Non-small cell lung cancer	Crizotinib	Biomarker analysis. Co-occurring RAS-MAPK pathway alterations, notably in KRAS and NF1, were associated with decreased response to MET inhibitor treatment in MET exon 14 skipping mutation-positive lung cancer.	31548343
GIMR	2022-10-11	FL	R2	KRAS	Amplification	Non-small cell lung cancer	Selpercatinib; Pralsetinib	Retrospective study. The study identified acquisition of RET kinase solvent front mutations (G810), as well as genomic amplification of MET and KRAS as potential bypass mechanisms.	33007380
GIMR	2020-09-15	FL	R2	KRAS	Amplification and NOT missense variant	Gastric cancer; Gastroesophageal junction adenocarcinoma; Oesophageal adenocarcinoma	Trametinib	Preclinical study. KRAS amplification in gastroesophageal cancer models results in insensitivity to MEK inhibition due to adaptive increase in KRAS-GTP levels, but combined MEK and SHP2 inhibition shows enhanced sensitivity, revealing a potential therapeutic strategy for KRAS-amplified tumors.	29808010
GIMR	2023-12-09	FL	R2	KRAS	Amplification, A11_G12delinsGD, G12R, G12S, G13D, H95N, Q61H, Q61L, R68S, Y96D	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2023-08-24	FL	R2	KRAS	Amplification, G12A, G12D, G12R, G12V, G13D, R68S, H95R, Y96D, Y96H, Y96N, Q99L, A146T, Oncogenic mutation AND NOT G12C	Non-small cell lung cancer; Colorectal adenocarcinoma; Solid tumours	Divarasib	Phase 1/2 single arm trial. GO42144. NCT04449874. Divarasib showed confirmed response rates of 53% in NSCLC and 29% in colorectal cancer patients. Serial ctDNA assessment identifying genomic alterations associated with response and potential acquired and treatment-emergent mutations.	37611121
GIMR	2020-05-31	FL	R2	KRAS	Amplification, G12D	Non-small cell lung cancer	Crizotinib	Biomarker analysis. Study on MET exon 14-mutant NSCLC. Acquired resistance to MET TKIs driven by on-target secondary MET mutations (35%) and off-target mechanisms including KRAS mutations (45%).	32034073
GIMR	2026-03-05	FL	R2	KRAS	Amplification, G12D, G12V, Q61H, G13D, G12A, G12R, G12S, G12L, G12F, Q61L, V8L, G12W, A146P, A146T, H95R, Y96N, H95Q, Y96H, M72I, M72T, H95D, H95N	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2020-05-27	FL	R2	KRAS	Amplification, G13D, A146V	Gastric cancer	Trastuzumab	Case-control study. AMNESIA. Biomarkers of primary resistance to trastuzumab in HER2-positive metastatic gastric cancer patients, showing significant association between presence of genomic alterations (including KRAS mutations/amplifications) and primary resistance, with median PFS 2.6 months versus 5.2 months.	29208673
GIMR	2021-12-17	FL	R2	KRAS	G12C	Colorectal adenocarcinoma	Sotorasib	Phase 2. CodeBreaK 100. N=62. In heavily previously treated colorectal cancer, single-agent Sotorasib yielded an ORR of 9.7% (6/62, all PR) with lower bound 95% CI not exceeding prespecified benchmark. Median DOR 4.2 months. Median OS 10 months. DCR 51/62 (82.3%).	10.1016/S1470-2045(21)00605-7
GIMR	2021-09-29	FL	R2	KRAS	G12C	Solid tumours	Entrectinib	Cell line study. Bypass mechenism of acquired resistance.	31124056
GIMR	2021-06-25	FL	R2	KRAS	G12C AND Amplification, G12D, G12R, G12V, G12W, G13D, Q61H, R68S, H95D, H95Q, H95R, Y96C	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: on-target acquired resistance identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample.	34161704
GIMR	2025-06-12	FL	R2	KRAS	G12R, Q61L, Q61R, Q61K	Solid tumours	ACBI3	Preclinical study. A single small-molecule degrader, ACBI3, was designed to target 13 of the 17 most prevalent oncogenic KRAS mutants, achieving potent and selective degradation, and inducing tumor regression in KRAS mutant xenograft mouse models.	39298590
GIMR	2025-06-11	FL	R2	KRAS	G12R, Q61L, Q61R, Q61K, A59T	Solid tumours	BI-2493; BI-2865	Preclinical study. A non-covalent pan-KRAS inhibitor was discovered, which binds to the inactive state of KRAS, blocking nucleotide exchange and inhibiting downstream signalling, proliferation, and tumour growth in KRAS mutant cancer cells and mice models.	37258666
GIMR	2026-03-11	FL	R2	KRAS	G12R, Q61R, Q61	Solid tumours	BBO-11818	Preclinical study. BBO-11818. Potent noncovalent pan-KRAS inhibitor targeting ON and OFF states of KRAS G12D, G12V, and G12C. Potently inhibited MAPK signaling and cellular viability in KRAS-driven cell lines. Produced tumor regressions in KRAS-mutant xenograft models. Enhanced efficacy observed in combination with anti-PD-1, anti-EGFR antibodies, and RAS:PI3Kα breaker.	41790032
GIMR	2020-03-12	FL	R2	KRAS	G12S	Non-small cell lung cancer	Osimertinib	Preclinical study and patient biopsy analysis. Heterogeneous mechanisms of resistance to third-generation EGFR inhibitors, including MET or ERBB2 amplification and KRAS(G12S) mutation, suggesting potential combination strategies such as EGFR/MEK dual inhibition to overcome resistance.	27252416
GIMR	2021-11-15	FL	R2	KRAS	G12V	Non-small cell lung cancer	Sotorasib	Phase 1/2 study findings. Multiple treatment-emergent alterations observed in 27 patients treated with sotorasib, including alterations in KRAS, NRAS, BRAF, and other genes, associated with resistance to KRAS(G12C) inhibition.	34759319
GIMR	2021-04-26	FL	R2	KRAS	G13D	Colorectal adenocarcinoma	Cetuximab; Cetuximab + Irinotecan	Phase 2 ICECREAM trial. N=51. Response rate was 0% with cetuximab monotherapy versus 9% with cetuximab plus irinotecan in patients with KRAS G13D mutation-positive metastatic colorectal cancer.	27114605
GIMR	2020-03-12	FL	R2	KRAS	G13D	Non-small cell lung cancer	Osimertinib	Preclinical study. KRAS G13D mutation was found in PC9-AZDR clones, conferring acquired resistance to mutation-selective EGFR tyrosine kinase inhibitors in non-small cell lung cancer cells.	28202511
GIMR	2022-08-12	FL	R2	KRAS	G13D, Q61K, Q61R	Solid tumours	SHP099; SHP099 + Trametinib	Cell line study. RAS G13D and Q61X predict resistance to SHP2 inhibitors	30605687
GIMR	2026-03-05	FL	R2	KRAS	H95L	Solid tumours	Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2026-03-05	FL	R2	KRAS	M72I	Solid tumours	Adagrasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2024-06-09	FL	R2	KRAS	Oncogenic mutation	Colorectal adenocarcinoma	Panitumumab + FOLFOX	Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months).	10.1200/JCO.2024.42.16_suppl.3507
GIMR	2021-10-06	FL	R2	KRAS	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
GIMR	2022-04-04	FL	R2	KRAS	Oncogenic mutations	Colorectal adenocarcinoma	Afatinib	Randomised Phase 2 trial. No activities is seen in Afatinib arm (ORR 0%, of 36) in KRAS mutant group.	25441408
GIMR	2023-12-19	FL	R2	KRAS	Oncogenic mutations	Colorectal cancer	Atezolizumab + Cobimetinib	Phase 3 IMblaze 370 trial. NCT02788279. N=363. Atezolizumab plus cobimetinib did not improve OS compared to regorafenib in patients with MSS colorectal cancer and disease progression on or intolerance to at least two previous chemotherapy regimens. ORR in RAS mutant group was 1/99 (1%).	31003911
GIMR	2020-04-25	FL	R2	KRAS	Oncogenic mutations	Non-small cell lung cancer	Ensartinib	Phase 2 trial. NCT03215693. Ensartinib showed activity in crizotinib-resistant, ALK-positive NSCLC patients with an ORR of 52% and intracranial ORR of 70% in patients with measurable brain metastases. Data updated 2025-06-14.	31628085
GIMR	2020-06-10	FL	R2	KRAS	Oncogenic mutations	Non-small cell lung cancer	Osimertinib	Biomarker analysis. In 155 tumor specimens with acquired EGFR-TKI resistance, mechanisms included EGFR T790M mutation (63%), HER2 amplification (13%), MET amplification (5%), and small cell transformation (3%), among others.	23470965
GIMR	2022-04-09	FL	R2	KRAS	Oncogenic mutations	Rhabdomyosarcoma; High-grade gliomas	Selumetinib	NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR.	35363510
GIMR	2020-04-16	FL	R2	KRAS	Oncogenic mutations	Solid tumours	MEK inhibitor	Intrinsic resistance due to bypass mechanisms, negative feedback, CRAF associations. Also narrow therapeutic index.	24685132, 24746704, 25435214
GIMR	2021-06-06	FL	R2	KRAS	Oncogenic mutations	Solid tumours	Selumetinib	Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed.	10.1200/JCO.2021.39.15_suppl.10008
GIMR	2021-06-12	FL	R2	KRAS	Oncogenic mutations	Solid tumours	Ulixertinib	Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%.	10.1200/JCO.2022.40.16_suppl.3009
GIMR	2022-08-03	FL	R2	KRAS	Q61H	Pancreatic acinar cell carcinoma	SHP099	Preclinical study. The Q61H mutation in KRAS confers resistance to SHP2 inhibitors by decoupling KRAS from upstream regulation, impairing GTP hydrolysis, and retaining high-affinity RAF interaction.	34725361
GIMR	2026-03-05	FL	R2	KRAS	R68S	Solid tumours	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2021-06-25	FL	R2	KRAS	V8L, G13D, V14L, K16T, A59S, Q61R, R68S, G77V, Y96D, Y96C, K117N, D119H, A146P	Solid tumours	Sotorasib	Phase1/2 study. N=38. KRAS(G12C) mutant cancers treated with adagrasib or sotorasib. Putative mechanisms of resistance detected in 45% patients, including acquired KRAS alterations, bypass mechanisms, and histologic transformation to squamous-cell carcinoma. On-target resistance identified by deep mutational scanning and in vitro validated.	34161704
GIMR	2021-06-25	FL	R2	KRAS	V9F, G13D, V14L, K16T, A59S, Q61R, E62D, Y64N, R68S, M72L, G77V, H95D, H95Q, H95R, Y96D, Y96C, Q99K, K117N, D119H, A146P	Solid tumours	Adagrasib	Phase 1/2 study. NCT03785249. N=38. Mechanisms of resistance to Adagrasib include acquired KRAS alterations (G12D/R/V/W, G13D, Q61H, R68S, H95D/Q/R, Y96C, and KRAS(G12C) allele amplification) and bypass mechanisms involving MET amplification, NRAS, BRAF, MAP2K1, RET mutations, ALK, RET, BRAF, RAF1, FGFR3 fusions, and NF1, PTEN loss-of-function mutations. Histologic transformation to squamous-cell carcinoma was observed in 2 lung adenocarcinoma patients.	34161704
GIMR	2026-03-05	FL	R2	KRAS	Y96D	Solid tumours	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2020-05-15	FL	R2	KRAS+MET	MET:exon 14 skipping mutation and KRAS:Oncogenic mutations	Non-small cell lung cancer	Crizotinib	KRAS mutation is identified as a mechanism of primary and secondary resistance to MET tyrosine kinase inhibitors in MET exon 14-mutant non-small cell lung cancer, with dual inhibition of MET or EGFR/ERBB2 and MEK showing potential as a therapeutic approach.	30352902
GIMR	2020-12-11	FL	R2	KRAS+Microsatellite Instability	KRAS:Oncogenic mutations AND Microsatellite Instability:High	Colorectal adenocarcinoma	Pembrolizumab	Phase 3 KEYNOTE-177 trial. NCT02563002. N=307. Pembrolizumab demonstrated superior progression-free survival (16.5 vs 8.2 months, HR 0.60) with reduced treatment-related adverse events (22% vs 66%) in MSI-H/dMMR metastatic colorectal cancer, with 83% of responders maintaining ongoing responses at 24 months. The KRAS subgroup did not show PFS benefit over chemotherapy.	33264544
GIMR	2020-12-11	FL	R2	KRAS+Mismatch repair	KRAS:Oncogenic mutations AND Mismatch repair:deficient	Colorectal adenocarcinoma	Pembrolizumab	Phase 3 KEYNOTE-177 trial. NCT02563002. N=307. Pembrolizumab demonstrated superior progression-free survival (16.5 vs 8.2 months, HR 0.60) with reduced treatment-related adverse events (22% vs 66%) in MSI-H/dMMR metastatic colorectal cancer, with 83% of responders maintaining ongoing responses at 24 months. The KRAS subgroup did not show PFS benefit over chemotherapy.	33264544
GIMR	2021-05-18	FL	R2	KRAS+NRAS	NOT KRAS:exon 2 mutation and NOT KRAS:exon 3 mutation and NOT KRAS:exon 4 mutation and NOT NRAS:exon 2 mutation and NOT NRAS:exon 3 mutation and NOT NRAS:exon 4 mutation	Colorectal adenocarcinoma	Duligotuzumab + FOLFIRI	Phase 2. NCT01652482. In RAS wild-type metastatic colorectal cancer, duligotuzumab plus FOLFIRI showed no improvement in PFS or OS compared with cetuximab and FOLFIRI, with a trend for lower ORR and different toxicity profiles.	29506988
GIMR	2022-10-16	FL	R2	KRAS+NRAS+BRAF	NOT KRAS:Oncogenic mutation and NOT NRAS:Oncogenic mutation and NOT BRAF:Oncogenic mutation	Breast cancer; Non-small cell lung cancer; Ovarian cancer	Cetuximab	Phase 2 TAPUR study. NCT02693535. N=49. Cetuximab showed no objective responses in breast cancer (N=10) and NSCLC (N=10), and no objective responses but 4 patients with stable disease for at least 16 weeks in ovarian cancer (N=29).	33090333
GIMR	2025-06-13	FL	R2	LGALS1	Protein expression	Oesophageal squamous cell carcinoma	Paclitaxel	Preclinical study. Galectin-1 is a key mediator of paclitaxel resistance in esophageal squamous cell carcinoma, acting through the interaction with β-catenin and enhancing MDR1 transcription, thereby increasing resistance to paclitaxel.	39186691
GIMR	2021-06-10	FL	R2	Loss-of-heterozygosity score	High	Non-small cell lung cancer	Rucaparib	Phase 2 Lung-MAP Sub-Study, S1900A. NCT03845296. N=64 (27 squamous; 37 non-squamous). Rucaparib showed limited efficacy in NSCLC patients with high genomic LOH and/or BRCA1/2 mutations, with an ORR of 7% (4% squamous; 9% non-squamous) and median PFS of 3.2 months (non-squamous) and 2.9 months (squamous). Genomic LOH does not predict activity. 	10.1200/JCO.2021.39.15_suppl.9024
GIMR	2025-07-02	FL	R2	LTK	F568C, L592F, G596R, L650F	Non-small cell lung cancer	Brigatinib; Entrectinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	R2	LTK	F568C, L650F	Non-small cell lung cancer	Repotrectinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	R2	LTK	G596R	Non-small cell lung cancer	Gilteritinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	R2	LTK	I565N, F568C, L590M, G596R, D597N, L650F, G663A	Non-small cell lung cancer	Crizotinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	R2	LTK	L590M, L592F, G596R, D597N, L650F	Non-small cell lung cancer	Alectinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	R2	LTK	L592F, L650F	Non-small cell lung cancer	Ceritinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2025-07-02	FL	R2	LTK	L650F	Non-small cell lung cancer	Lorlatinib	Preclinical study. CLIP1-LTK fusion. LTK mutations, particularly L650F, confer resistance to lorlatinib in NSCLC with CLIP1-LTK fusion, with gilteritinib shown to overcome L650F-mediated resistance; in silico analysis indicates L650F reduces lorlatinib-LTK binding affinity.	38575808
GIMR	2020-11-26	FL	R2	LZTR1	Loss-of-function mutations	Chronic myelogenous leukaemia	Imatinib; Ponatinib	Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance	30442766
GIMR	2021-10-22	FL	R2	MAP2K1	C121S	Melanoma	Vemurafenib	Progression biopsy study identified MEK C121S as the downstream mechanism for acquired resistance to Vemurafenib.	21383288
GIMR	2023-12-09	FL	R2	MAP2K1	E203K, K57N, Q56P	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-11-25	FL	R2	MAP2K1	F53L	Colorectal adenocarcinoma	Dabrafenib + Trametinib; Trametinib	Paired pre-post treatment sequencing identified MAPK pathway alterations, including KRAS amplification, BRAF amplification, and MEK1 mutation, driving clinical acquired resistance to RAF inhibitor combinations in BRAF-mutant colorectal cancer.	25673644
GIMR	2021-06-25	FL	R2	MAP2K1	K57T, I99_K104del, E102_I103del	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2023-04-20	FL	R2	MAP2K1	K757E, K57N	Colorectal adenocarcinoma	Cetuximab; Panitumumab	RTK alterations and MAP2K1 mutations occur in approximately 8% of colorectal carcinoma cases, often associated with wild-type RAS/RAF, and confer resistance to anti-EGFR and/or anti-ERBB2 therapy.	26660078
GIMR	2021-11-10	FL	R2	MAP2K1	L98_K104delinsQ	Histiocytosis	Trametinib	Preclinical study. MAP2K1 L98_K104delinsQ identified in Langerhans cell histiocytosis confers resistance to MEK inhibitor trametinib and causes auto-activation of ERK pathway in vitro.	29768711
GIMR	2020-04-16	FL	R2	MAP2K1	P124L, Q56P	Melanoma	Selumetinib	Preclinical study. MEK1 mutations, particularly those affecting the allosteric drug binding pocket, alpha-helix C, and N-terminal negative regulatory helix (helix A), confer resistance to MEK and B-RAF inhibition in BRAF-mutant melanoma.	19915144
GIMR	2023-08-24	FL	R2	MAP2K1	Q56P, K57N, E203K	Non-small cell lung cancer; Colorectal adenocarcinoma; Solid tumours	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2026-03-05	FL	R2	MAP2K1	R47_E62delinsQ, Q56P, K57N, K57T, E102_I103del, E203K	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2020-05-20	FL	R2	MAP2K1+BRAF	MAP2K1:P124 and BRAF:V600	Melanoma	Vemurafenib; Dabrafenib	Retrospective analysis. 123 patients with BRAF V600-mutant metastatic melanoma showed preexisting MEK1 P124 mutations (N=12, 10%) were associated with poorer RECIST response (33% vs 72%) and shorter PFS (3.1 vs 4.8 months), indicating a subset of patients likely to benefit from combination therapies involving MEK or ERK inhibitors due to intrinsic resistance mechanism.	25370473
GIMR	2021-10-22	FL/JG	R2	MAP2K2	C125S, V35M, L46F, N126D 	Melanoma	Dabrafenib; Trametinib; Dabrafenib + Trametinib	Progression biopsy and cell line studies. Acquired C125S (and lesser degree, V35M, L46F, and N126D) confersresistance to both RAF and MEK inhibition.	24265153
GIMR	2020-05-31	FL	R2	MAP2K2	Q60P	Melanoma	Trametinib	Preclinical study. Concurrent MEK2-Q60P mutation and BRAF amplification/V600E were identified in melanoma cells resistant to BRAF and MEK inhibitors, conferring sustained MAPK activation and on-target resistance, which was addressed by a triple combination of dabrafenib, trametinib, and GSK2126458.	24055054
GIMR	2021-04-28	FL	R2	MAPK1	Y131F, A189V, S202P, D321G, E322K	Melanoma	Dabrafenib + Trametinib	Cell line mutagenesis screen following RAF/MEKi exposure	25320010
GIMR	2021-04-28	FL	R2	MAPK1	Y36N, Y36H, P58S, P58L, P58T, Y64N, C65Y	Melanoma	VX11E	Cell line mutagenesis screen following ERKi exposure	25320010
GIMR	2021-04-28	FL	R2	MAPK3	C82Y, R84H, Q90R, Y148H, A206V, S219P	Melanoma	Dabrafenib + Trametinib	Cell line mutagenesis screen following RAF/MEKi exposure	25320010
GIMR	2021-04-28	FL	R2	MAPK3	Y53H, G54A, S74G, P75L, Y81C, C82Y, G186D	Melanoma	VX11E	Cell line mutagenesis screen following ERKi exposure	25320010
GIMR	2020-11-17	FL	R2	MDM2	Amplification	Solid tumours	Cabozantinib	Preclinical study. MDM2 amplification identified as a potential mechanism of primary or acquired resistance to cabozantinib in RET-rearranged lung cancers, with MDM2 inhibitors showing effectiveness in suppressing tumor growth.	10.1200/JCO.2016.34.15_suppl.9068
GIMR	2023-07-04	FL	R2	MET	Amplification	Colorectal adenocarcinoma	Cetuximab; Panitumumab	Preclinical study. Amplification of the MET gene is associated with acquired resistance to EGFR targeted therapy in patients with metastatic colorectal cancer; MET inhibitors could be effective in overcoming this resistance.	23729478
GIMR	2023-07-04	FL	R2	MET	Amplification	Colorectal adenocarcinoma	Cetuximab; Panitumumab	MET amplification is rare in primary colorectal cancer but occurs in a significant number of patients who are refractory to anti-EGFR therapy identified through circulating-free DNA.	27421137
GIMR	2023-12-09	FL	R2	MET	Amplification	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-06-09	FL	R2	MET	Amplification	Extramammary Paget’s disease	Trastuzumab	Case report. A patient with ERBB2(S310F) mutated metastatic extramammary Paget's disease initially responded to trastuzumab and carboplatin, but developed resistance with additional genomic alterations including ERBB3(A232V) and PIK3CA(G106V) mutations and MET and CDK6 amplification.	31803359
GIMR	2022-08-07	FL	R2	MET	Amplification	Lung adenocarcinoma; Medullary thyroid cancer	Selpercatinib	Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers.	35304457
GIMR	2020-05-04	FL	R2	MET	Amplification	Non-small cell lung cancer	Gefitinib; Erlotinib; Afatinib; Dacomitinib; Osimertinib	Preclinical and clinical study. Clonal MET amplification, observed in 3% of treatment-naive EGFR-mutant NSCLC, was associated with suboptimal response to EGFR TKI, highlighting its role as a determinant of TKI resistance.	30676858
GIMR	2020-03-12	FL	R2	MET	Amplification	Non-small cell lung cancer	Osimertinib	Secondary resistance post Osimertinib. MET amplification determined by FISH, liquid biopsy.	27252416, 37938348
GIMR	2022-10-11	FL	R2	MET	Amplification	Non-small cell lung cancer	Selpercatinib; Pralsetinib	Retrospective study. The study identified acquisition of RET kinase solvent front mutations (G810), as well as genomic amplification of MET and KRAS as potential bypass mechanisms.	33007380
GIMR	2021-06-25	FL	R2	MET	Amplification	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2020-05-27	FL	R2	MET	Amplification, N375S	Gastric cancer	Trastuzumab	Case-control study (AMNESIA). Identified biomarkers (EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications) associated with primary resistance to trastuzumab in HER2-positive metastatic gastric cancer patients, with significantly shorter PFS (2.6 vs 5.2 months) and OS (7.6 vs 16.1 months).	29208673
GIMR	2021-01-03	FL	R2	MET	D1228N (D1246N)	Non-small cell lung cancer	Crizotinib	Case report. Acquired D1228N mutation in MET kinase domain identified as a potential resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping using targeted next-generation sequencing.	27343442
GIMR	2020-05-15	FL	R2	MET	D1228N (D1246N)	Triple-negative breast cancer	Crizotinib	Case report. MET D1228N mutation emerged during progression on crizotinib in MET-amplified triple-negative breast cancer, conferring resistance to crizotinib but retaining sensitivity to cabozantinib.	32234363
GIMR	2020-05-31	FL	R2	MET	D1228N (D1246N), D1228 (D1246)	Non-small cell lung cancer	Capmatinib; Tepotinib; Savolitinib	On-target secondary MET kinase domain mutations and off-target mechanisms including KRAS mutations and amplifications in KRAS, EGFR, HER3, and BRAF drive resistance to MET TKIs in MET exon 14-mutant NSCLC.	32034073
GIMR	2025-05-27	FL	R2	MET	D1228N, Y1230H	Non-small cell lung cancer	Elzovantinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2025-05-27	FL	R2	MET	D1228N, Y1230H	Non-small cell lung cancer	Tepotinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2021-01-03	FL	R2	MET	D1246N (D1228N)	Non-small cell lung cancer	Crizotinib	Case report. Emergent variant post exposure to Crizotinib. Possible Acquired resistance	31809977
GIMR	2021-01-03	FL	R2	MET	F1007fs (F1025fs)	Non-small cell lung cancer	Crizotinib	Case report. Novel MET Exon 14 skipping treatment-naive lung adenocarcinoma presented primary resistance to crizotinib.	29935852
GIMR	2021-01-03	FL	R2	MET	G1163R (G1181R), D1228H (D1246N), D1228A (D1246A), Y1230H (Y1248A)	Non-small cell lung cancer	Crizotinib	Case report. Emergent mutations detected on ctDNA at the time progression after treatment with crizotinib.	29110851
GIMR	2020-05-31	FL	R2	MET	H1094Y (H1112Y), L1195V (L1213V)	Non-small cell lung cancer	Glesatinib	Preclinical study. Study analysed tissue or plasma NGS data from 20 MET exon 14-mutant NSCLC patients at the time of MET TKI resistance, identifying on-target (MET kinase domain mutations, MET exon 14-mutant allele amplification) and off-target (KRAS mutations, EGFR, HER3, BRAF amplifications) resistance mechanisms in 75% of patients.	32034073
GIMR	2020-05-15	FL	R2	MET	L1195V (L1213V), Y1230 (Y1248), D1228N (D1246N), D1228 (D1246), D1246 (D1228), Y1248 (Y1230), G1163 (G1181)	Non-small cell lung cancer	Crizotinib	Evidence for Crizotinib and potential sequential use of type II MET inhibitors (cabozantinib, glesatinib, merestinib) in NSCLC patients with MET exon 14 skipping mutations after developing resistance to type I MET inhibitors.	28522754, 27987579, 32306194, 32034073
GIMR	2025-05-27	FL	R2	MET	L1195V, D1228N, Y1230H	Non-small cell lung cancer	Crizotinib 	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2025-05-27	FL	R2	MET	L1195V, F1200I, M1250T	Non-small cell lung cancer	Cabozantinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2021-06-10	FL	R2	MET	No protein expression	Non-small cell lung cancer	Amivantamab + Lazertinib	Phase 1 CHRYSALIS. ORR 10% (1 in 10 patients) with negative IHC (defined as combined EGFR+MET H score < 400)	10.1200/JCO.2021.39.15_suppl.9006
GIMR	2020-05-22	FL	R2	MET	Overexpression	Gastric cancer	Infigratinib; AZD4547; Rogaratinib	Preclinical studies on FGFR1-amplified lung cancer cell lines identified diverse mechanisms of primary and acquired drug resistance to FGFR inhibitors, including NRAS amplification, DUSP6 deletion, and MET upregulation/amplification, which reactivate MAPK pathway and confer resistance, suggesting rational combination therapies to improve FGFR inhibitor treatments.	28630215, 27429073
GIMR	2020-11-10	FL	R2	MET	Overexpression	Lung squamous cell carcinoma	Telisotuzumab Vedotin	Lung-MAP S1400K, Selected based on H-Score (>150). ORR 9%	33125909, 33221175, 10.1200/JCO.2019.37.15_suppl.9075
GIMR	2021-01-03	FL	R2	MET	Y1230C (Y1248C)	Non-small cell lung cancer	Crizotinib	Case report. MET Y1230C mutation (0.3% pre-treatment frequency) emerged as a resistance mechanism to crizotinib in NSCLC with MET exon 14 skipping, co-occurring with METex14 alteration D1010H, and was detected in ctDNA at progression after 13 months of treatment.	27666659
GIMR	2021-01-03	FL	R2	MET	Y1230H (Y1248H)	Non-small cell lung cancer	Crizotinib	Case report. Preexisting MET Y1230C mutation confers acquired resistance to crizotinib in NSCLC with MET exon 14 skipping, detected at low frequency pretreatment and in ctDNA at progression.	28629543
GIMR	2025-05-27	FL	R2	MET	Y1230H, D1228N	Non-small cell lung cancer	Capmatinib	Preclinical study and case reports. Activating MET tyrosine kinase domain point mutations identified in diverse cancers are oncogenic and sensitive to MET inhibitors, with two lung adenocarcinoma patients achieving partial responses to a type I MET inhibitor.	38564707
GIMR	2021-01-03	FL	R2	MET	Y1230S (Y1248S), D1228N (D1246N), D1228H (D1246H), F1200I (F1218I), L1195V (L1213V), S244fs	Non-small cell lung cancer	Crizotinib	Retrospective analysis. Targeted sequencing analysis of 289 patients with METex14-mutated NSCLC revealed co-occurring RAS-MAPK pathway alterations associated with decreased MET TKI treatment response, and preclinical models showed that combining crizotinib with MEK inhibitor trametinib overcame this resistance.	31548343
GIMR	2021-01-03	FL	R2	MET+TP53	MET:Exon 14 skipping mutation and TP53:Oncogenic mutations	Non-small cell lung cancer	Crizotinib	Case series. Co-occurring RAS-MAPK pathway alterations (e.g., KRAS, NF1) are associated with decreased response to MET inhibitors in METex14-mutated NSCLC. Combined inhibition of MET and MEK signaling overcomes this resistance in preclinical models. TP53 mutation was observed in 7 of 12 cases following crizotinib exposure.	31548343
GIMR	2026-03-04	FL	R2	MGMT	Unmethylated	Glioblastoma	Ipilimumab + Nivolumab	Phase II/III. NRG Oncology BN007. NCT04396860. N=159. Ipilimumab and nivolumab did not improve PFS over temozolomide (7.7 versus 8.5 months, HR 1.47) or OS (median approximately 13 months each, HR 0.95) in newly diagnosed MGMT-unmethylated glioblastoma. Accrual closed permanently.	40779733
GIMR	2021-08-15	FL	R2	Microsatellite Instability	Stable	Colorectal adenocarcinoma	Atezolizumab; Atezolizumab + Cobimetinib	Phase 3 IMblaze370 trial. NCT02788279. Atezolizumab with or without cobimetinib did not improve OS versus regorafenib in microsatellite-stable metastatic colorectal cancer, with an ORR of 4/273 (1%) in the atezolizumab groups, highlighting the challenge of expanding immunotherapy benefits to tumours with lower baseline immune inflammation.	31003911
GIMR	2023-07-14	FL	R2	Microsatellite Instability	Stable	Endometrial cancer	Durvalumab	Phase 2 trial. PHAEDRA. NCT03015129. Durvalumab demonstrated an objective tumor response rate of 47% in mismatch repair-deficient (dMMR) endometrial cancer versus 3% (1 of 35) in mismatch repair-proficient (pMMR) tumors, with median progression-free survival of 1.8 months in the pMMR group.	34103352
GIMR	2025-04-23	FL	R2	Microsatellite instability+Mismatch repair	NOT Microsatellite instability:high AND NOT Mismatch repair:deficient	Colorectal adenocarcinoma	FOLFOX + Bevacizumab + Durvalumab + Oleclumab 	Phase 1B/2. COLUMBIA-1. NCT04068610. N=59. Durvalumab + oleclumab added to FOLFOX and bevacizumab did not significantly improve ORR (62% vs 46%) in metastatic microsatellite-stable colorectal cancer.	39048638
GIMR	2023-03-02	FL	R2	Microsatellite instability+Mismatch repair	NOT Microsatellite instability:high AND NOT Mismatch repair:deficient	Colorectal adenocarcinoma	Nivolumab + FLOX	Randomized Phase 2. METIMMOX trial. NCT03388190. N=80. In microsatellite stable disease, alternating FLOX + nivolumab showed no PFS advantage over FLOX alone (9.2 months each).	38664577
GIMR	2022-06-20	FL	R2	Mismatch repair	Deficient	High-grade gliomas	Pembrolizumab	Single-agent pembrolizumab showed a DCR of 31% with no objective responses (ORR 0%) and four patients with stable disease in a prospective study of 13 recurrent high-grade gliomas with MMR protein loss.	32823925
GIMR	2021-08-04	FL	R2	Mismatch repair	Deficient	High-grade gliomas; Anaplastic astrocytoma; Glioblastoma	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	A case-control series showed no response to PD-L1 blockade in 11 HGG patients with hypermutant and mismatch repair-deficient HGG. High TMB is associated with few clonal neoantigens and no immunogenic responses in glioma populations.	32322066
GIMR	2021-06-24	FL	R2	Mismatch repair	Deficient	High-grade gliomas; Anaplastic astrocytoma; Glioblastoma	Pembrolizumab	Phase 2 trial. N=13. Median age 43 years. ORR 0%. DCR 31% (4 stable disease). TMB ranged 6.8-23.4 mutations/megabase. Pembrolizumab showed no apparent benefit in patients with recurrent HGG and MMR loss.	32823925
GIMR	2023-07-14	FL	R2	Mismatch repair	Proficient, NOT Deficient	Endometrial cancer	Durvalumab	Phase 2 trial. NCT03015129. Durvalumab showed  activity in dMMR advanced endometrial carcinoma with ORR of 47% and median PFS of 8.3 months, but limited activity in pMMR advanced endometrial carcinoma with ORR of 3% and median PFS of 1.8 months.	34103352
GIMR	2021-11-15	FL	R2	MRAS	Q71R	Non-small cell lung cancer	Sotorasib	Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models.	34759319
GIMR	2021-09-29	FL	R2	MTOR	F2108L	Anaplastic thyroid cancer 	Everolimus	F2108L confers resistance to allosteric mTOR inhibition	25295501
GIMR	2023-12-09	FL	R2	MYC	Amplification	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2024-02-26	FL	R2	MYC	Amplification	Small-cell lung cancer	Cisplatin + Etoposide; Carboplatin + Etoposide; Olaparib + Temozolomide; Topotecan	Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients.	38386926
GIMR	2025-06-30	FL	R2	MYC	Amplification	Solid tumours; Prostate cancer	Berzosertib	Phase 1/2. NCT03718091. Cohort T3 (solid tumors with RS-associated mutations). Patients did not demonstrate significant PFS improvement (median PFS 4 months) despite observed target engagement (pCHK1 reduction) and no clinical benefit.	39453756
GIMR	2024-02-26	FL	R2	MYCL	Amplification	Small-cell lung cancer	Cisplatin + Etoposide; Carboplatin + Etoposide; Olaparib + Temozolomide; Topotecan	Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients.	38386926
GIMR	2025-06-25	FL	R2	MYCL	Amplification, Overexpression	Small-cell lung cancer	Mivebresib	Preclinical study. SCLC cell lines with MYC or MYCN amplification were sensitive to BET inhibitor mivebresib, while MYCL1 amplified lines were resistant, with silencing of MYC or MYCN partially rescuing cells from mivebresib's antiproliferative effects, and unique enhancer binding preferences identified for MYC, MYCN, and MYCL1.	38747975
POTTR	2020-04-26	FL	R2	MYCN	Amplification	Prostate cancer	Androgen receptor antagonist; GnRH agonist; CYP17A1 inhibitor; Enzalutamide; Apalutamide	Preclinical study. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer, highlighting restored AR signalling, AR bypass signalling, and complete AR independence as potential resistance mechanisms.	26563462
GIMR	2024-02-26	FL	R2	MYCN	Amplification	Small-cell lung cancer	Cisplatin + Etoposide; Carboplatin + Etoposide; Olaparib + Temozolomide; Topotecan	Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients.	38386926
GIMR	2023-12-09	FL	R2	NF1	Deletion	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-11-26	FL	R2	NF1	Loss-of-function mutations	Chronic myelogenous leukaemia	Imatinib; Nilotinib; Dasatinib; Bosutinib; Ponatinib	Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance	30442766
GIMR	2020-07-03	FL	R2	NF1	Loss-of-function mutations	Triple-negative breast cancer	Cetuximab	Case report. A patient with EGFR-amplified heavily pretreated metastatic triple-negative breast cancer experienced a dramatic response to cetuximab as 7th-line treatment, with disease progression occurring 8 months after treatment initiation, and molecular analysis suggested loss of EGFR phosphorylation and acquisition of an NF1 mutation as potential resistance mechanisms.	35100682
GIMR	2021-10-06	FL	R2	NF1	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
GIMR	2022-04-09	FL	R2	NF1	Oncogenic mutations	High-grade gliomas	Selumetinib	NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR.	35363510
GIMR	2021-01-03	FL	R2	NF1	Oncogenic mutations	Non-small cell lung cancer	Crizotinib	Preclinical study and cfDNA analysis of 289 patients showed co-occurring RAS-MAPK pathway alterations limit response to MET inhibitors in MET exon 14 skipping mutation-positive lung cancer, and resistance was overcome by combining crizotinib with MEK inhibitor trametinib.	31548343
GIMR	2023-04-19	FL	R2	NF1	Oncogenic mutations	Solid tumour	Trametinib	Phase 2. NCI-MATCH. NCT02465060. EAY131. In NF1 cohort, ORR was 4% (2 responders in 46 patients). PFS was 1.9 months.	37053535
GIMR	2021-06-12	FL	R2	NF1	Oncogenic mutations	Solid tumours	Ulixertinib	Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%.	10.1200/JCO.2022.40.16_suppl.3009
GIMR	2021-06-25	FL	R2	NF1	R2637*	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2021-12-12	FL	R2	NF1+KIT	NF1:Oncogenic mutations AND NOT KIT:Oncogenic mutations	Gastrointestinal stromal tumour	Imatinib	In a case series of NF1-associated GIST treated with imatinib, primary resistance was shown in three patients. 	18628470
GIMR	2021-06-07	FL	R2	NF2	Loss-of-function mutations	Solid tumours	Defactinib	NCI-MATCH Arm U: ORR 3% (1/31) with the only responder in choroid meningioma. PFS 1.3 months. NCT04439331	10.1200/JCO.2021.39.15_suppl.3087
SuboKB	2020-04-16	FL	R2	NOTCH2	Rearrangements	Triple-negative breast cancer	MRK003	Preclinical study. NOTCH1 mutations and high N1-ICD levels correlated with GSI sensitivity in TNBC and ACC, while NOTCH2 rearrangements were associated with GSI resistance in TNBC cell lines.	25104330
GIMR	2025-12-15	FL	R2	NRAS	Amplification	Colorectal adenocarcinoma	Cetuximab; Panitumumab; FOLFIRI + Cetuximab; Irinotecan + Cetuximab; FOLFOX + Panitumumab	Case report	28178681
GIMR	2020-04-23	FL	R2	NRAS	Amplification	Melanoma	Imatinib	Phase 2 trial of imatinib in metastatic melanoma with KIT amplifications and/or mutations, showing effectiveness in tumors with KIT mutations (54% response rate) but not in those with KIT amplifications only, with potential resistance mechanisms including NRAS mutations and KIT copy number gain.	23775962
GIMR	2023-12-09	FL	R2	NRAS	Amplification, G13R, Q61R	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2026-03-05	FL	R2	NRAS	Amplification, Q61K, Q61R, Q61L, Y96H, G13R, Q61H, A146V	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2021-06-08	FL	R2	NRAS	G12, G13, Q61	Solid tumours except melanoma	Binimetinib	Phase 2 NCI-MATCH trial. NRAS subprotocol. Single-agent binimetinib showed limited efficacy with an ORR of 2%. Notably, a patient with malignant ameloblastoma harboring a codon 61 NRAS mutation achieved a durable partial response, and patients with colorectal cancer bearing a NRAS codon 61 mutation had significantly longer OS and PFS compared to those with codon 12 or 13 mutations.	33637626
GIMR	2024-02-26	FL	R2	NRAS	G12C	Solid tumour	Adagrasib; GDC6036	Preclinical study. Both adagrasib and GDC6036 are KRAS G12C specific inhibitors.	38236605
GIMR	2023-08-24	FL	R2	NRAS	G13R	Colorectal adenocarcinoma	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2024-06-09	FL	R2	NRAS	Oncogenic mutation	Colorectal adenocarcinoma	Panitumumab + FOLFOX	Exploratory analysis of phase 3 PARADIGM study (N=802). Acquired gene alteration was associated with shorter post-progression survival in panitumumab + FOLFOX group, particularly with RTK/RAS alterations (13.2 vs 18.8 months).	10.1200/JCO.2024.42.16_suppl.3507
MoSTLLy	2023-01-12	XT	R2	NRAS	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	Phase 1 trial. NCT02074839. N=174. Multiple mechanisms of resistance to ivosidenib have been identified in IDH1-mutant relapsed/refractory AML. Primary resistance is associated with RTK pathway mutations, while acquired resistance involves second-site IDH1/IDH2 mutations that restore 2-HG production. NRAS mutations are associated with reduced response rates compared to wild-type NRAS.	32380538
GIMR	2021-06-12	FL	R2	NRAS	Oncogenic mutations	Rhabdomyosarcoma	Ulixertinib	Phase 2. Pediatric MATCH Arm J (APEC1621J). NCT03698994. In paediatric population with treatment-refractory tumors (N=20) harbouring activating MAPK alterations, ORR was 0%.	10.1200/JCO.2022.40.16_suppl.3009
GIMR	2022-04-09	FL	R2	NRAS	Oncogenic mutations	Rhabdomyosarcoma; Neuroblastoma	Selumetinib	NCI-COG Pediatric MATCH Trial. Arm E. NCT03213691. N=20 with MAPK pathway gene alterations with no objective responses observed. Three patients achieved stable disease as BOR.	35363510
GIMR	2026-03-11	FL	R2	NRAS	Oncogenic mutations	Solid tumours	BBO-11818	Preclinical study. BBO-11818. Potent noncovalent pan-KRAS inhibitor targeting ON and OFF states of KRAS G12D, G12V, and G12C. Potently inhibited MAPK signaling and cellular viability in KRAS-driven cell lines. Produced tumor regressions in KRAS-mutant xenograft models. Enhanced efficacy observed in combination with anti-PD-1, anti-EGFR antibodies, and RAS:PI3Kα breaker.	41790032
GIMR	2021-06-06	FL	R2	NRAS	Oncogenic mutations	Solid tumours	Selumetinib	Phase 2. NCI-COG arm E. N=21. Pediatric with MAPK pathway alterations. No objective responses was observed.	10.1200/JCO.2021.39.15_suppl.10008
GIMR	2024-07-19	FL	R2	NRAS	Q61H, G13D, G12D	Cancer of unknown primary	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2020-10-30	FL	R2	NRAS	Q61K	Neuroblastoma	SHP099; II-B08; RMC-4550	Cell line study showed that NB cell line is sensitive to SHP2 inhibition (NRAS WT) but resistant to in vivo model with NRAS Q61K. Combining SHP2i with MEKi or ERKi reversed the resistance.	32586982
GIMR	2021-06-25	FL	R2	NRAS	Q61K	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2021-03-24	FL	R2	NRAS	Q61K, G12C	Acute myeloid leukaemia	Gilteritinib	Mutations in MAPK pathway mediate secondary clinical resistance to FLT3-mutated AML	31088841
GIMR	2021-11-15	FL	R2	NRAS	Q61K, G13R	Non-small cell lung cancer	Sotorasib	Treatment-emergent RAS and RAF hotspot mutations were also observed in both clinical samples and patient-derived xenograft models.	34759319
GIMR	2021-10-22	FL	R2	NRAS	Q61R, Q61K	Melanoma	Dabrafenib; Trametinib; Dabrafenib + Trametinib	Progression biopsy study. Acquired NRAS Q61 mutation confers resistance to both RAF and MEK inhibition.	24265153
GIMR	2024-07-19	FL	R2	NRAS	Q61R, Q61K, G13V, G13D, G12S	Cholangiocarcinoma	Pemigatinib	Phase 2. FIGHT-207 basket. NCT03822117. Acquired resistance mutations following Pemigatinib.	38710951
GIMR	2021-06-08	FL	R2	NRG1	Fusions	Non-small cell lung cancer	Pembrolizumab + Carboplatin + Pemetrexed	Retrospective registry-based study. NRG1 fusion-positive lung cancers showed heterogeneity in molecular, pathological, and clinical characteristics, with low ORR to platinum-doublet chemotherapy (13%), taxane-based chemotherapy (14%), chemoimmunotherapy (0%), and single-agent immunotherapy (20%), while afatinib achieved an ORR of 25%.	34077268
GIMR	2020-11-03	FL	R2	NRG1	Overexpression	Non-small cell lung cancer	Seribantumab + Docetaxel	No PFS improvement in EGFR wt NSCLC	10.1200/JCO.2019.37.15_suppl.9036
GIMR	2021-03-24	FL	R2	NTRK1	Alterations AND NOT fusion	Solid tumours	Larotrectinib	Pooled analysis of larotrectinib trials. For non-fusion NTRK1/2/3 alterations, only one response was seen (of 73) with short duration of response.	10.1158/1538-7445.AM2020-CT062
GIMR	2025-02-17	FL	R2	NTRK1	F589L, G595R, G667A, G667C, G667S	Solid tumours	Selitrectinib, Zurletrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	R2	NTRK1	F589L, G595R, G667A, G667C, G667S, V573M	Solid tumours	Larotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	R2	NTRK1	G595R, G667A, G667C, G667S	Solid tumours	Repotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2021-09-15	FL	R2	NTRK1	High mRNA expression	Solid tumours	Larotrectinib	Phase 2 trial. ACTRN12619001147178. Larotrectinib showed limited efficacy in tumors with NTRK overexpression (ORR 0%).	39720993
GIMR	2021-03-24	FL	R2	NTRK2	Alterations AND NOT fusion	Solid tumours	Larotrectinib	Pooled analysis of larotrectinib trials. For non-fusion NTRK1/2/3 alterations, only one response was seen (of 73) with short duration of response.	10.1158/1538-7445.AM2020-CT062
GIMR	2025-02-17	FL	R2	NTRK2	F633L, G639R, G709C	Solid tumours	Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2021-09-15	FL	R2	NTRK2	High mRNA expression	Solid tumours	Larotrectinib	Phase 2 trial. ACTRN12619001147178. Larotrectinib showed limited efficacy in tumors with NTRK overexpression (ORR 0%).	39720993
GIMR	2021-03-24	FL	R2	NTRK3	Alterations AND NOT fusion	Solid tumours	Larotrectinib	Pooled analysis of larotrectinib trials. For non-fusion NTRK1/2/3 alterations, only one response was seen (of 73) with short duration of response.	10.1158/1538-7445.AM2020-CT062
GIMR	2025-02-17	FL	R2	NTRK3	F617L, G623R, G623E, G696A, G696C	Solid tumours	Larotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	R2	NTRK3	F617L, G623R, G696A, G696C	Solid tumours	Selitrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	R2	NTRK3	F617L, G623R, G696C	Solid tumours	Zurletrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2025-02-17	FL	R2	NTRK3	G623R, G623E, G696C	Solid tumours	Repotrectinib	Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models.	38902532
GIMR	2021-09-15	FL	R2	NTRK3	High mRNA expression	Solid tumours	Larotrectinib	Phase 2 trial. ACTRN12619001147178. Larotrectinib showed limited efficacy in tumors with NTRK overexpression (ORR 0%).	39720993
GIMR	2021-03-16	FL	R2	PALB2	Oncogenic mutations	Lung squamous cell carcinoma	Talazoparib	Phase 2 S1400G study. NCT02154490. Talazoparib demonstrated limited activity in homologous recombination repair-deficient squamous cell lung cancer with ORR of 4% in primary analysis population and 11% in full eligible population.	33583720
GIMR	2025-04-23	FL	R2	PALB2	Reversion mutations	Prostate cancer	Olaparib	Biomarker analysis. In patient enrolled in TOPARP-B trial, reversion mutations were identified in 79% of BRCA2/PALB2-mutated tumors, correlating with improved radiological progression-free and overall survival.	39577422
GIMR	2025-02-05	FL	R2	PAXIP1	Oncogenic mutations	Breast cancer	Olaparib	Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.	38244928
GIMR	2021-08-04	FL	R2	PDGFRA	Amplification	Sarcoma; Intimal sarcoma	Imatinib	Single-centre experience of case series in intimal sarcomas. No objective response to imatinib in 4 patients treated with PDGFR amplification.	28501860
GIMR	2022-01-25	FL	R2	PDGFRA	D842V	Gastrointestinal stromal tumour	Imatinib	Preclinical study. Various PDGFRA mutations showed different in vitro sensitivity to imatinib, with exon 12 and 14 mutations being imatinib-sensitive, while most exon 18 mutations, particularly D842V, were imatinib-resistant, except for D842Y, D846Y, N848K, Y849K, and HDSN845-848P. (Entry updated/corrected 2025-05-28.)	15928335
GIMR	2022-01-25	FL	R2	PDGFRA	D842V	Gastrointestinal stromal tumour	Imatinib; Sorafenib; Sunitinib	Preclinical study. Sorafenib inhibits various KIT and PDGFRA kinase mutations associated with imatinib and sunitinib resistance in gastrointestinal stromal tumors, except for substitutions at KIT codon D816 and PDGFRA codon 842.	22665524
GIMR	2020-05-15	FL	R2	PDGFRA	D842V	Gastrointestinal stromal tumour	Imatinib; Sunitinib	Preclinical study. Sorafenib inhibits various KIT and PDGFRA mutant kinases associated with imatinib-resistant or sunitinib-resistant gastrointestinal stromal tumors (GIST), except for substitutions at KIT codon D816 and PDGFRA codon 842.	14645423, 22665524
GIMR	2020-04-23	FL	R2	PDGFRA	D842V	Gastrointestinal stromal tumour	Imatinib; Sunitinib; Regorafenib	Preclinical studies and case reports. Type II c-Kit inhibitors are sensitive to KIT D816 and PDGFR842V mutations	29093181
GIMR	2025-07-07	FL	R2	PDGFRA	D842V and V654A, D842V and T674R  	Gastrointestinal stromal tumour	Avapritinib	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2025-07-07	FL	R2	PDGFRA	D842V, D842V and V654A, D842V and T674R  	Gastrointestinal stromal tumour	Imatinib; Sunitinib; Regorafenib; Ripretinib; Nintedanib; Bezuclastinib; IDRX-42; NB003	Retrospective analysis. KIT ATP-binding pocket (AP)/activation loop (AL) mutations in cis identified in 50% of ripretinib-resistant GISTs, conferring resistance despite prior efficacy of ripretinib in imatinib-resistant GISTs, with no effective inhibitors against AP/AL mutations except limited activity of nintedanib and PDGFRA inhibitors.	38408285
GIMR	2022-01-25	FL	R2	PDGFRA	FIP1L1-PDGFRA fusion and T674I	Chronic eosinophilic leukaemia	Imatinib; Nilotinib; Sorafenib	Case report. A patient with FIP1L1-PDGFRA-positive chronic eosinophilic leukemia developed imatinib resistance due to T674I mutation, and showed limited clinical activity to subsequent nilotinib and sorafenib treatments.	21818111
GIMR	2020-05-15	FL	R2	PDGFRA	FIP1L1-PDGFRA fusion and T674I	Mastocytosis	Imatinib	FIP1L1-PDGFRA fusion tyrosine kinase is identified as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome, with relapse correlating with the appearance of a T674I mutation in PDGFRA that confers resistance to imatinib.	12660384
GIMR	2020-06-30	FL	R2	PDGFRA	Overexpression	Soft tissue sarcomas	Olaratumab + Doxorubicin	ANNOUNCE trial. Negative Phase 3. No benefit over doxorubicin in PDGFRA overexpression subgroup.	32259228
POTTR	2020-04-16	FL	R2	PDGFRA	Protein expression	Soft tissue sarcomas	Olaratumab	Preclinical study. Olaratumab, a PDGFRA antibody, showed no significant antitumor effects as a single agent or in combination with doxorubicin in a panel of patient-derived soft tissue sarcoma xenografts.	31331295
GIMR	2021-06-02	FL	R2	PIK3CA	Amplification, Oncogenic mutations	Solid tumours	Everolimus	Phase 2 Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.	28330462
GIMR	2023-08-24	FL	R2	PIK3CA	E545K	Colorectal adenocarcinoma	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2023-12-09	FL	R2	PIK3CA	E545K	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-03-12	FL	R2	PIK3CA	G118D	Non-small cell lung cancer	Osimertinib	Preclinical study. Amplification of EGFR wild-type alleles was found to confer acquired resistance to mutation-selective EGFR tyrosine kinase inhibitors, with the Src-AKT pathway also contributing to resistance.	28202511
GIMR	2021-06-25	FL	R2	PIK3CA	H1047R	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2022-06-20	FL	R2	PIK3CA	H1047R	Solid tumours	LOXO-783; LOXO-783 + Fulvestrant; LOXO-783 + Letrozole; LOXO-783 + Anaztrozole; LOXO-783 + Paclitaxel	Phase 1a/b PIKASSO-01 trial. NCT05307705. LOXO-783, a PI3Kα H1047R inhibitor, demonstrated mutant selectivity and reduced hyperglycemia, with objective response rates (ORR) and clinical benefit rates (CBR) of 3%/17% in monotherapy, 5%/19% with endocrine therapy, and 19%/25% when combined with paclitaxel, though limited by high rates of diarrhea.	10.1158/1557-3265.SABCS24-PS7-03
GIMR	2020-05-27	FL	R2	PIK3CA	N345T, H1047R, H1047L	Gastric cancer	Trastuzumab	Case-control study. AMNESIA. Patients with HER2-positive metastatic gastric cancer and no alterations in the AMNESIA panel (EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications) had significantly longer median PFS (5.2 vs 2.6 months) and OS (16.1 vs 7.6 months). 	29208673
GIMR	2023-11-21	FL	R2	PIK3CA	Oncogenic mutation	Glioblastoma	Buparlisib	Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months.	30715997
GIMR	2020-11-15	FL	R2	PIK3CA	Oncogenic mutations	Breast cancer	Pictilisib + Fulvestrant	Phase 2 FERGI trial. NCT01437566. Pictilisib + fulvestrant did not improve PFS over placebo + fulvestrant in oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer patients with or without PIK3CA mutations.	27155741
GIMR	2020-11-15	FL	R2	PIK3CA	Oncogenic mutations	Breast cancer	Pictilisib + Paclitaxel	Phase 2 PEGGY trial. NCT01740336. N=183. Pictilisib did not improve PFS over placebo (8.2 vs 7.8 months) or response rate in combination with paclitaxel for hormone receptor-positive, HER2-negative breast cancer.	27573562
GIMR	2020-07-30	FL	R2	PIK3CA	Oncogenic mutations	Colorectal adenocarcinoma	MK2206	Phase 2 trial. NCT01802320. Biomarker-enriched, previously treated metastatic colorectal cancer patients received MK2206, an oral AKT inhibitor, with no radiographic responses, median PFS of 1.8 months, and median OS of 6.8 months. ORR was 0% in patients with PIK3CA mutations (0/2).	10.1200/JCO.2016.34.15_suppl.3563
GIMR	2021-12-17	FL	R2	PIK3CA	Oncogenic mutations	Endometrial cancer	LY3023414	N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months	31880826
GIMR	2020-11-10	FL	R2	PIK3CA	Oncogenic mutations	Lung squamous cell carcinoma	Taselisib	Phase 2 Lung-MAP S1400B trial. NCT02785913. Taselisib showed limited efficacy with 5% response rate (1/21) in patients with PIK3CA-altered squamous NSCLC, with median PFS 2.9 months and OS 5.9 months.	31158500, 33125909
GIMR	2023-05-07	FL	R2	PIK3CA	Oncogenic mutations	Non-small cell lung cancer	Aumolertinib	The most common mechanisms of resistance to Aumolertinib were acquired EGFR C797S mutation and aberration in PIK3CA bypass track.	10.1016/j.jtho.2022.07.739
GIMR	2020-06-10	FL	R2	PIK3CA	Oncogenic mutations	Non-small cell lung cancer	Osimertinib	Biomarker analysis. Analysis of 155 EGFR-mutant lung cancer patients with acquired resistance to EGFR-TKI therapy, including off-target mechanism.	23470965
GIMR	2022-10-16	FL	R2	PIK3CA	Oncogenic mutations	Solid tumours except Breast cancer, Gastric cancer, Lung squamous cell carcinoma	Taselisib	NCT02465060. NCI-MATCH (EAY131) Subprotocol I. N=61. ORR 0%. PFS rate at 6 months was 20%.	35138919
GIMR	2021-08-06	FL	R2	PIK3CA	Oncogenic mutations, E542K, E545K, E545, H1074R, Q546X	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Ipatasertib + FOLFOX	Randomised phase 2 trial. JAGUAR. No significant PFS benefit was observed in the addition of ipatasertib to FOLFOX or in subgroups with PI3KCA/AKT-alteration.	30592991
GIMR	2021-09-30	FL	R2	PIK3CA	Oncogenic mutations; Amplification	Solid tumours	Buparlisib	Phase 2. NCT01833169. Single-agent Buparlisib has limited clinical activity (ORR 1.4%) in PI3K pathway altered solid tumours.	31741715
GIMR	2023-11-21	FL	R2	PIK3R1	Oncogenic mutation	Glioblastoma	Buparlisib	Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months.	30715997
GIMR	2021-12-17	FL	R2	PIK3R1	Oncogenic mutations	Endometrial cancer	LY3023414	N=28 with 25 Evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months	31880826
GIMR	2021-09-30	FL	R2	PIK3R1	Oncogenic mutations	Solid tumours	Buparlisib	Phase 2. NCT01833169. Single-agent Buparlisib has limited clinical activity (ORR 1.4%) in PI3K pathway altered solid tumours.	31741715
GIMR	2021-06-25	FL	R2	PIK3R1	S361fs	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2023-12-09	FL	R2	PIK3R2	G373R	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-12-11	FL	R2	PPP2R2A	Oncogenic mutations	Prostate cancer	Olaparib	PROFOUND trial; Cohort B. No OS benefit or cell line data to suggest PPP2R2A Is synthetically lethal with Olaparib.	32343890, 32955174
GIMR	2021-06-12	FL	R2	PTCH1	Oncogenic mutations	Solid tumours	Vismodegib	Phase 2. NCT02465060. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol T. N=34. In 22 of 31 evaluable and MATCH confirmed patient, ORR was 9.1% with 6 month PFS of 22%. In all 31 evaluable patients, ORR was 7% (2/31).	10.1200/JCO.2022.40.16_suppl.3010
GIMR	2023-08-24	FL	R2	PTEN	Deletion	Solid tumours	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2024-04-30	FL	R2	PTEN	Deletion, Loss of protein expression	Glioblastoma	Everolimus	Preclinical study. Glioblastoma orthotopic xenograft test panel. PTEN loss did not predict response to everolimus with only 1 of 7 PTEN-disrupted lines showing sensitivity.	18559622
GIMR	2020-07-30	FL	R2	PTEN	Loss of protein expression	Colorectal adenocarcinoma	MK2206	Phase 2 trial. NCT01802320. Biomarker-enriched, previously treated metastatic colorectal cancer patients received MK2206, an oral AKT inhibitor, with no radiographic responses, median PFS of 1.8 months, and median OS of 6.8 months. ORR was 0% in PTEN loss patients (0/9).	10.1200/JCO.2016.34.15_suppl.3563
GIMR	2022-02-23	FL	R2	PTEN	Loss of protein expression	Glioblastoma	Lapatinib	Phase 1/2 trial of lapatinib in recurrent glioblastoma multiforme; PTEN loss was seen in 6 out of 16 patients, but no correlation was observed with outcome and PTEN status. ORR 0%. 	19499221
GIMR	2021-06-02	FL	R2	PTEN	Loss of protein expression, Loss-of-function mutations	Solid tumours	Everolimus	Phase 2 Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.	28330462
GIMR	2021-12-17	FL	R2	PTEN	Loss-of-function mutations	Endometrial cancer	LY3023414	"Phase 2 study. N=28 with 25 evaluable patients. ORR 16%. CBR 28%. Median PFS 2.5 months. Median OS 9.2 months. LY3023414, a dual PI3K/mTOR inhibitor, showed modest activity in heavily pretreated advanced endometrial cancer with PI3K pathway mutations, but no correlation between molecular alterations and response was observed.	31880826
GIMR	2023-11-22	FL	R2	PTEN	Loss-of-function mutations, deletion	Breast cancer	Trastuzumab	Preclinical study. Trastuzumab treatment increased the phosphatase activity of PTEN via Src inhibition. Patients with PTEN deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. 	15324695
GIMR	2023-11-27	FL	R2	PTEN	Loss-of-function mutations, deletion	Solid tumour	Talazoparib	Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.	36253484
GIMR	2021-09-30	FL	R2	PTEN	Loss-of-function mutations, loss of protein expression	Solid tumours	Buparlisib	Phase 2. NCT01833169. Single-agent Buparlisib has limited clinical activity (ORR 1.4%) in PI3K pathway altered solid tumours.	31741715
GIMR	2020-04-16	FL	R2	PTEN	Loss-of-function mutations, loss of protein expression	Solid tumours	GSK2636771	Phase 2 NCI-MATCH trial. NCT02465060. Modest activity observed with GSK2636771 in patients with PTEN mutation/deletion or protein loss, with 1 partial response (4.5%) and 9 stable diseases (32% and 37.5% in Arms N and P respectively) in 56 treated patients.	10.1093/annonc/mdy279.406
GIMR	2021-06-25	FL	R2	PTEN	N48K, G209V	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2021-03-16	FL	R2	PTEN	Oncogenic mutations	Pancreatic adenocarcinoma	Olaparib	Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. PTEN (N=2)	33662100
GIMR	2023-12-09	FL	R2	PTEN	Oncogenic mutations, Deletion	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2021-08-06	FL	R2	PTEN	Oncogenic mutations, Loss-of-function mutations, Loss of protein expression	Gastroesophageal junction adenocarcinoma; Gastric Cancer	Ipatasertib + FOLFOX	Randomised phase 2 trial. JAGUAR. No significant PFS benefit was observed in the addition of ipatasertib to FOLFOX or in subgroups with PI3KCA/AKT-alteration.	30592991
GIMR	2023-11-21	FL	R2	PTEN	Oncogenic mutations; Deletions; Loss of protein expression	Glioblastoma	Buparlisib	Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months.	30715997
GIMR	2022-02-04	FL	R2	PTPN11	E76K	Solid tumours	RMC-4550	Preclinical study. RMC-4550, a potent SHP2 allosteric inhibitor, showed efficacy in cancer models with PTPN11 mutation-associated drivers, including class 3 BRAF mutants, NF1 loss, and KRASG12C, by disrupting SOS1-mediated RAS-GTP loading, resulting in tumour growth inhibition and regressions in vivo.	30104724
GIMR	2020-11-26	FL	R2	PTPN11	Loss-of-function mutations	Chronic myelogenous leukaemia	Imatinib; Nilotinib; Dasatinib; Ponatinib	Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance	30442766
GIMR	2021-10-06	FL	R2	PTPN11	Oncogenic mutations	Acute myeloid leukaemia	Ivosidenib	RTK pathway mutations are associated with primary resistance to ivosidenib	32380538
GIMR	2020-10-30	FL	R2	PTPN11	P491Q	Solid tumours	SHP099	Preclinical study. SHP2 inhibition by SHP099 prevents adaptive resistance to MEK inhibitors in multiple cancer models by impeding SOS/RAS/MEK/ERK1/2 reactivation and blocking ERK1/2-dependent transcriptional programs.	30045908
GIMR	2022-02-04	FL	R2	RAC1	P29S	Solid tumours	RMC-4550	Preclinical study. Cell line study SHP2 phosphatase inhibition by RMC-4550 disrupts SOS1-mediated RAS-GTP loading, decreasing oncogenic RAS/RAF/MEK/ERK signalling in cancers driven by RAS-GTP-dependent oncogenic BRAF, NF1 loss, and nucleotide-cycling oncogenic KRAS." 	30104724
GIMR	2023-11-27	FL	R2	RAD50	Oncogenic mutation	Solid tumour except Breast cancer	Talazoparib	Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.	36253484
GIMR	2023-01-18	FL	R2	RAD51C	Loss of promoter methylation	Ovarian cancer	Rucaparib; Niraparib	Preclinical study. In high-grade ovarian cancer, homozygous RAD51C promoter methylation predicts sensitivity to PARP inhibitors. Single unmethylated gene copy confers resistance to PARP inhibitors. 	34321239
GIMR	2021-03-16	FL	R2	RAD51C	Oncogenic mutations, Oncogenic mutations (germline)	Pancreatic adenocarcinoma	Olaparib	Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.	33662100
GIMR	2021-01-12	FL	R2	RAF1	Fusion; GATM-RAF1 fusion	Pancreatic acinar cell carcinoma	Trametinib	Case report. Pancreatic acinar cell carcinoma with RAF1 fusion demonstrated inferior response to MEK inhibitor therapy with no objective response. Concomitant CDKN2A loss was reported.	35100731
GIMR	2021-01-12	FL	R2	RAF1	Fusion; QKI-RAF1 fusion; SRGAP3-RAF1 fusion	Low-grade gliomas	Vemurafenib; FORE8394	Preclinical study. CRAF gene fusions in pediatric low-grade gliomas are unresponsive to RAF inhibitors due to robust protein-protein interactions mediated by the N-terminal non-kinase fusion partner, but are sensitive to pan-RAF dimer inhibitor LY3009120 and combinatorial inhibition of MAPK/mTOR pathway.	28806393
GIMR	2026-03-05	FL	R2	RAF1	K53T	Non-small cell lung cancer; Colorectal adenocarcinoma	Sotorasib; Adagrasib; Divarasib	Retrospective genomic analysis and preclinical study. N=143. KRASG12C mutated NSCLC and CRC treated with KRASG12C inhibitors. 46% developed RAS/MAPK alterations post-progression (CRC 69% vs NSCLC 26%). Preclinical efficacy demonstrated RM-018 activity against switch-II pocket mutations, Pan KRAS-IN-1 targeting KRAS-activating mutations, and RMC-7797 high potency across all RAS alterations.	39914665
GIMR	2022-02-04	FL	R2	RAF1	P261L	Solid tumours	RMC-4550	Cell line study. Preclinical study. SHP2 phosphatase inhibition with RMC-4550 disrupts SOS1-mediated RAS-GTP loading, decreasing oncogenic RAS/RAF/MEK/ERK signalling and cancer growth in human cancer models with RAS-GTP-dependent oncogenic BRAF, NF1 loss, or nucleotide-cycling oncogenic KRAS.	30104724
GIMR	2021-06-25	FL	R2	RAF1	RAF1-CCDC176 fusion, RAF1-TRAK1 fusion, Fusions	Solid tumours	Adagrasib	Phase 1/2. KRYSTAL-1. Off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of Adagrasib exposure, detected via tissue or ctDNA from blood samples. Acquired resistance to KRAS(G12C) inhibitors occurs through diverse genomic and histologic mechanisms, including acquired KRAS alterations, bypass mechanisms such as MET amplification and oncogenic fusions, and histologic transformation.	34161704
GIMR	2022-01-15	FL	R2	RAF1	S257P, P261T, G356E, G361A, S427T, D447N, M469I, E478K, R554K	Solid tumours	PLX4720	Cell line study. Random mutagenesis screen identified CRAF mutations confering resistance to RAF inhibitors.	23737487
GIMR	2021-06-08	FL	R2	RASA1	Loss-of-function mutations	Langerhans cell sarcoma	Vemurafenib + Cobimetinib	Case report. RASA1 loss identified as a mechanism of resistance to BRAF inhibitor in a BRAF V600-mutated Langerhans cell sarcoma patient.	30977771
GIMR	2023-08-24	FL	R2	RB1	Deletion	Solid tumours	Divarasib	Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations	37611121
GIMR	2025-06-09	FL	R2	RB1	Deletion, Oncogenic mutations	Epithelioid sarcoma; Atypical teratoid rhabdoid tumor	Tazemetostat	Preclinical study. Identified molecular mechanisms of tazemetostat resistance in SMARCB1-deficient tumors, and developed a combination strategy using AURKB targeting to circumvent resistance.	38315003
GIMR	2025-06-24	FL	R2	RB1	Deletion, Oncogenic mutations, Loss of protein expression	Head and neck squamous cell carcinoma	Alisertib + Pembrolizumab 	Phase 1/2 trial. Alisertib + Pembrolizumab demonstrated no objective responses but achieved prolonged stable disease in several patients. Among 15 HPV-positive patients, 4 experienced stable disease ≥6 months. Median overall survival was 16.8 months and median progression-free survival was 1.4 months.	39589337
GIMR	2022-06-17	FL	R2	RB1	Heterozygous deletion, Copy number loss, Loss-of-function mutation	Breast cancer	Ribociclib; Palbociclib; Abemaciclib	Heterozygous loss of RB1 is associated with decreased PFS on CDK4/6 inhibitor and endocrine therapy.	10.1200/JCO.2022.40.16_suppl.1010
GIMR	2020-05-15	FL	R2	RB1	Loss-of-function mutations	Breast cancer; Solid Tumours	Palbociclib; Ribociclib; Abemaciclib	Phase 3 PALOMA-3 trial analysis. Acquired mutations in ESR1 (notably Y537S) and PIK3CA emerged as resistance mechanisms to palbociclib plus fulvestrant, with RB1 mutations also emerging in a minority of patients (4.7%) on the palbociclib arm.	30206110
GIMR	2024-10-08	FL	R2	RB1	Oncogenic mutation	Breast cancer	Ribociclib	Pooled analysis of the MONALEESA study. Significantly more alterations in the RB1 and SPEN genes at the point of progression compared to baseline in patients from the ribociclib arm.	39313156
GIMR	2023-03-31	FL	R2	RB1	Oncogenic mutations	Non-small cell lung cancer	Trastuzumab deruxtecan	Case series. The emergence of acquired resistance to trastuzumab deruxtecan in TP53-/HER2-mutated non-small-cell lung cancer may be correlated with the loss of Rb1.	36809053
POTTR	2020-04-26	FL	R2	RB1	Oncogenic mutations	Prostate cancer	Androgen receptor antagonist; GnRH agonist; CYP17A1 inhibitor; Enzalutamide; Apalutamide	Review. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer were discussed, including restored AR signalling, AR bypass signalling, and complete AR independence, presenting new challenges for long-term disease control.	26563462
GIMR	2023-04-05	FL	R2	RBM10	Loss-of-function mutations	Non-small cell lung cancer	Osimertinib	Preclinical and retrospective observational study. RBM10 loss is associated with reduced response to Osimretinib in EGFR-mutant non-small cell lung cancer models and cohort.	35579943
GIMR	2023-12-09	FL	R2	RET	CCDC6-RET fusion	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2021-06-25	FL	R2	RET	CCDC6-RET fusion	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2020-06-10	FL	R2	RET	Fusion	Non-small cell lung cancer	Osimertinib	Biomarker analysis. 155 EGFR-mutant lung cancer patients revealed EGFR T790M mutation (63%) as the most common mechanism of acquired resistance to EGFR-TKI therapy, followed by MET amplification (5%), HER2 amplification (13%), small cell transformation (3%), and other off-target mechanism including RET fusion.	23470965
GIMR	2020-11-17	FL	R2	RET	G810A	Solid tumours	Vandetanib	Preclinical study. KIF5B-RET fusion lung adenocarcinoma modeled in transgenic mice and cell lines, showing ponatinib as the most effective inhibitor against KIF5B-RET and its drug-resistant mutants, and identifying novel vandetanib-resistant RET(G810A) mutation.	27496134, 32083997
GIMR	2022-01-07	FL	R2	RET	G810A, G810S, G810C, G810R	Non-small cell lung cancer	Selpercatinib	Preclinical study and Case report. RET G810 solvent front mutations mediate acquired resistance to selpercatinib in RET-driven malignancies through steric hindrance of drug binding.	31988000
GIMR	2022-10-11	FL	R2	RET	G810S, G810R	Non-small cell lung cancer	Selpercatinib; Pralsetinib	Retrospective study. The study identified acquisition of RET kinase solvent front mutations (G810), as well as genomic amplification of MET and KRAS as potential bypass mechanisms.	33007380
GIMR	2020-11-17	FL	R2	RET	G810S, G810R	Solid tumours	Selpercatinib; Pralsetinib		10.1093/annonc/mdz244.068, 32083997
GIMR	2020-11-17	FL	R2	RET	I788N	Solid tumours	Ponatinib; Vandetanib; Cabozantinib; Ceritinib; Crizotinib; Regorafenib; Sorafenib; Alectinib	Preclinical study. RET-rearranged tumors. Potent inhibitors AD80 and ponatinib that bind in the DFG-out conformation of RET selectively kill RET-rearranged tumors, while mechanisms of resistance include CCDC6-RET(I788N) mutation and MAPK pathway reactivation.	28615362
GIMR	2020-11-17	FL	R2	RET	KIF5B-RET fusion	Non-small cell lung cancer	Agerafenib		31710864
GIMR	2021-06-25	FL	R2	RET	M918T	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2020-11-17	FL	R2	RET	S904F	Solid tumours	Vandetanib	Preclinical and clinical studies. Resistance mechanisms to RET inhibitors in RET-dependent cancers, including a secondary RET mutation S904F in the activation loop conferring resistance to vandetanib, and highlighted the need for next-generation RET inhibitors to overcome resistance.	29434222, 32083997
GIMR	2020-11-17	FL	R2	RET	V804L, V804M	Solid tumours	Vandetanib; Cabozantinib	Preclinical study. RET(V804L) and RET(G810A) gatekeeper mutations confer resistance to RET inhibitors, but can be overcome by next-generation inhibitors such as ponatinib and lenvatinib	15184865, 27496134, 32083997
GIMR	2020-11-17	FL	R2	RET	V804M	Solid tumours	Vandetanib; Cabozantinib; Ceritinib; Crizotinib; Regorafenib; Sorafenib; Alectinib	Preclinical study. RET-rearranged tumors. Potent inhibitors AD80 and ponatinib that bind in the DFG-out conformation of RET selectively kill RET-rearranged tumors, while mechanisms of resistance include CCDC6-RET(I788N) mutation and MAPK pathway reactivation.	28615362
GIMR	2022-08-07	FL	R2	RET	Y806C, G810C, G801S	Lung adenocarcinoma; Medullary thyroid cancer	Selpercatinib	Preclinical study. Selpercatinib resistance in RET-driven lung and thyroid cancers is driven by MAPK pathway reactivation via secondary RET solvent front mutations, MET amplifications, or selection of RET-wildtype tumor cell populations with alternative mitogenic drivers.	35304457
GIMR	2021-02-02	FL	R2	RET	Y806C, Y806N, G810C, G810S, V738A	Medullary thyroid cancer	Selpercatinib; Pralsetinib	Case report. Acquired resistance after treatment with Selpercatinib habouring KIF5B-RET fusion detected by cfDNA. Cell line cross-profiling of additional resistant mutations.	33161056
GIMR	2025-02-05	FL	R2	RIF1	Oncogenic mutations	Breast cancer	Olaparib	Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.	38244928
GIMR	2021-06-25	FL	R2	RIT1	P128L	Solid tumours	Adagrasib	Phase 1/2 KRYSTAL-1: off-target acquired resistance mechanism identified by treatment-emergent mutations after 12 weeks of exposure to Agagrasib, identified on tissue or ctDNA from blood sample. 	34161704
GIMR	2020-04-25	FL	R2	ROS1	E1395G, L1947R, G1971E, S1986Y, S1986F, L2026M, G2032R, D2033N, S2060G, V2098U, L2155S	Non-small cell lung cancer	Crizotinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2020-04-25	FL	R2	ROS1	F2004C, F2075V, D2113G	Non-small cell lung cancer	Cabozantinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437, 25351743
GIMR	2020-04-25	FL	R2	ROS1	G2032R	Non-small cell lung cancer	Lorlatinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2023-04-14	FL	R2	ROS1	G2032R	Solid tumours	Crizotinib; Entrectinib; Loratinib	Preclinical study. ROS1 fusions and secondary resistance mutationsof earlier-generation TKIs.	36511802
GIMR	2020-04-25	FL	R2	ROS1	G2032R, D2033N	Non-small cell lung cancer	Ensartinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2024-06-02	FL	R2	ROS1	G2101A, G2032R, L2026M, S1986F	Non-small cell lung cancer	Crizotinib	Phase 2. TRUST-I study. NCT04395677. N=173. Taletrectinib showed high ORR (91% in TKI-naive, 52% in crizotinib-pretreated). PFS was NR (TKI-naive) and 7.6 months (crizotinib-pretreated.)	38822758, 10.1200/JCO.2024.42.16_suppl.8520
GIMR	2023-12-09	FL	R2	ROS1	GOPC-ROS1 fusion	Colorectal adenocarcinoma	Divarasib; Divarasib + Cetuximab	Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC.	38052910
GIMR	2020-04-25	FL	R2	ROS1	L1951R, G2032R, D2033N, G2101A, L2155S	Non-small cell lung cancer	Ceritinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2020-04-25	FL	R2	ROS1	L1951R, L2026M, G2032R, D2033N	Non-small cell lung cancer	Brigatinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2020-04-25	FL	R2	ROS1	L2026M, G2032R	Non-small cell lung cancer	AZD3463	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2020-04-25	FL	R2	ROS1	L2026M, G2032R, D2033N	Non-small cell lung cancer	Entrectinib	Preclinical studies. Secondary resistance mutation in ROS1-rearranged NSCLC was observed, and profiling studies revealed structural features distinguishing ROS1 kinase domains.	26372962, 31395437
GIMR	2021-03-08	FL	R2	ROS1+MET	ROS1:fusion AND MET:D1228N	Non-small cell lung cancer	Crizotinib	Case report. A patient with metastatic lung adenocarcinoma with CD74-ROS1 fusion developed resistance to crizotinib through an acquired MET D1228N mutation and showed short-term disease control with cabozantinib.	33000474
GIMR	2025-06-30	FL	R2	SDHA	Oncogenic mutation	Gastrointestinal stromal tumour	Berzosertib	Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response.	39453756
GIMR	2025-06-30	FL	R2	SDHB	Oncogenic mutation	Gastrointestinal stromal tumour	Berzosertib	Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response.	39453756
GIMR	2025-06-30	FL	R2	SDHC	Oncogenic mutation	Gastrointestinal stromal tumour	Berzosertib	Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response.	39453756
GIMR	2025-06-30	FL	R2	SDHD	Oncogenic mutation	Gastrointestinal stromal tumour	Berzosertib	Phase 1/2 Translational study of berzosertib in four cohorts. NCT03718091. N=29. In Cohort T4, SDH-deficient GIST showed longest median PFS (229 days) with stable disease as best response.	39453756
GIMR	2022-07-27	FL	R2	SETD2	Truncating mutations	Non-clear cell renal cell carcinoma	Cabozantinib + Nivolumab	NCT03635892. Single arm in Non-clear cell renal cell carcinomas. In non-chromophobe group, the overall ORR was 48%. In exploratory biomarker analysis, SETD2 truncating mutation was associated with reduced response with Cabozantinib and Nivolumab (0 of 5 cases).	35298296
GIMR	2021-12-15	FL	R2	SMARCA4	Oncogenic mutations	Solid tumours	Cisplatin	SMARCA4/2 loss reduces apoptosis induced by chemotherapy through disrupting intracellular organelle calcium ion release via IP3R3-mediated mechanism.	34518526
GIMR	2025-08-18	FL/NZ	R2	SMARCA4	Oncogenic mutations, Loss of protein expression	Solid tumours; Atypical teratoid rhabdoid tumour; Malignant rhabdoid tumor; Ewing sarcoma; Epithelioid sarcoma; Histiocytosis; Renal medullary carcinoma; Hepatocellular carcinoma; Ependymoma; Chordoma; Peripheral T-cell lymphoma	Tazemetostat	Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%)	37228094
GIMR	2022-06-08	FL	R2	SMARCB1	Oncogenic mutations	Solid tumours	Tazemetostat	Phase 2 NCI-COG Pediatric MATCH trial Arm C. NCT03213665. N=20. Tazemetostat showed limited objective response (ORR 5%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but achieved prolonged stable disease in 33% of patients, suggesting potential disease stabilization.	10.1200/JCO.2022.40.16_suppl.10009
GIMR	2025-08-18	FL/NZ	R2	SMARCB1	Oncogenic mutations, Loss of protein expression	Solid tumours; Atypical teratoid rhabdoid tumour; Malignant rhabdoid tumor; Ewing sarcoma; Epithelioid sarcoma; Histiocytosis; Renal medullary carcinoma; Hepatocellular carcinoma; Ependymoma; Chordoma; Peripheral T-cell lymphoma	Tazemetostat	Phase 2. NCI-COG Pediatric MATCH APEC1621C. NCT03213665. N=20. Tazemetostat did not meet primary endpoint of ORR (5%, 90% CI 1%-20%) in pediatric patients with tumors harboring EZH2 mutations or SMARCB1/SMARCA4 loss, but 25% had prolonged stable disease (6+ months), with 6-month PFS 35% (95% CI 15.7-55.2%) and OS 45% (95% CI 23.1-64.7%)	37228094
GIMR	2021-02-28	FL	R2	SMO	D473, E518	Medulloblastoma	Vismodegib	Preclinical study. GDC-0449-resistant SMO mutants identified with D473H and E518 mutations	21123452
SuboKB	2020-04-25	ST	R2	SMO	D473G, D473Y, D473H, G497W, V321M, W281L, Q477E, A327P, C390R, D506N, E181K, E481G, G453D, K519R, K564E, L221P, L353F, N476K, P513L, P698T, P739L, P739S, R168H, R199Q, T336I, T349I, T349P, T534I, T548I, T640A, V386A, V404M, V414A, A459V, D384N, E518K, I408V, N219D, S387N, T241M, V281C	Basal cell carcinoma; Solid tumours	Vismodegib; Sonidegib	Preclinical and clinical studies demonstrated hedgehog signaling inhibitors' activity in various solid and hematological cancers, including pancreatic cancer, medulloblastoma, and leukemia, with SMO mutations identified as a key resistance mechanism in basal cell carcinoma.	21771911, 25759019, 25759020, 31125907
SuboKB	2020-04-25	ST	R2	SMO	D473H	Medulloblastoma	Vismodegib	Preclinical study. Genomic analysis of basal cell carcinoma tumor biopsies revealed On-target resistance to vismodegib associated with Hedgehog pathway reactivation through SMO mutation and SUFU and GLI2 copy number changes.	19726788, 21771911
GIMR	2022-03-04	FL	R2	SMO	D477G, E522K, G457S, S391N, D388N, N223D, L225R	Basal cell carcinoma; Medulloblastoma	Vismodegib; Sonidegib	Preclinical study. Itraconazole and arsenic trioxide inhibit Hedgehog pathway activation, showing activity against tumors with acquired resistance to Smoothened antagonists, including SMO(D477G) mutant.	23291299
GIMR	2021-06-12	FL	R2	SMO	P641A, W535L, L412F	Solid tumours	Vismodegib	Phase 2. NCT02465060. NCI-MATCH ECOG-ACRIN Trial (EAY131) Subprotocol T. N=34. In 22 of 31 evaluable and MATCH confirmed patient, ORR was 9.1% with 6 month PFS of 22%. In all 31 evaluable patients, ORR was 7% (2/31).	10.1200/JCO.2022.40.16_suppl.3010
GIMR	2024-10-08	FL	R2	SPEN	Oncogenic mutations	Breast cancer	Ribociclib	Pooled analysis of the MONALEESA study. Significantly more alterations in the RB1 and SPEN genes at the point of progression compared to baseline in patients from the ribociclib arm.	39313156
GIMR	2020-04-16	ST/FL	R2	STK11+KRAS	STK11:Oncogenic mutations AND KRAS:Oncogenic mutations	Non-small cell lung cancer	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	Preclinical study and retrospective observational analysis. STK11/LKB1 mutations in KRAS-mutant lung adenocarcinoma are associated with resistance to PD-1 inhibitors, resulting in lower ORR (7.4% vs 35.7% and 28.6%) and diminished PFS and OS 	29773717
GIMR	2021-02-28	FL	R2	SUFU	Loss-of-function mutations	Basal cell carcinoma	Vismodegib	Preclinical study. Genomic analysis of basal cell carcinoma tumor biopsies revealed vismodegib resistance associated with Hedgehog pathway reactivation through SMO mutation and SUFU and GLI2 copy number changes, suggesting combination therapies targeting multiple levels of the Hedgehog pathway may overcome resistance.	25759019
GIMR	2025-04-13	FL	R2	TACSTD2	T256R	Breast cancer	Sacituzumab Govitecan	Sacituzumab govitecan resistance mechanisms identified through RNA and whole-exome sequencing of pre-treatment and post-progression specimens, including TROP2T256R missense mutation and TOP1 E418K resistance mutation.	34404686
GIMR	2025-04-13	FL	R2	TOP1	E418K	Breast cancer	Sacituzumab Govitecan	Sacituzumab govitecan resistance mechanisms identified through RNA and whole-exome sequencing of pre-treatment and post-progression specimens, including TROP2T256R missense mutation and TOP1 E418K resistance mutation.	34404686
GIMR	2025-02-03	FL	R2	TOP1	L721R	Non-small cell lung cancer	Patritumab deruxtecan	Phase 1 U31402-A-U102 trial. N=102/78 (safety/efficacy). Patritumab deruxtecan (HER3-DXd) showed cORR of 41% and median OS of 16.2 months in EGFR-mutated NSCLC after EGFR TKI and platinum-based chemotherapy, with acquired mutations in ERBB3 and TOP1 potentially conferring resistance to HER3-Dxd.	38369013
GIMR	2023-08-30	FL	R2	TP53	Oncogenic mutations	Diffuse Midline Glioma	ONC201	Drug screening. Reduced sensitivity to ONC201 was found in DIPG cell lines harbouring TP53 mutantion.	37145169
GIMR	2023-07-11	FL	R2	TP53	Oncogenic mutations	Gastric cancer; Gastroesophageal junction adenocarcinoma	Berzosertib + Irinotecan	Phase 2 . NCT03641313. In patients with TP53-mutated gastric and gastro-esophageal junction adenocarcinoma, irinotecan and berzosertib did not meet the primary endpoint of ORR of 6% (1/16). Median PFS 4.0 months. Median overall OS 6.2 months.	10.1200/JCO.2023.41.16_suppl.4044
POTTR	2020-04-26	FL	R2	TP53	Oncogenic mutations	Prostate cancer	Androgen receptor antagonist; GnRH agonist; CYP17A1 inhibitor; Enzalutamide; Apalutamide	Preclinical study. Emerging mechanisms of resistance to androgen receptor inhibitors in prostate cancer were reviewed, including restored AR signalling, AR bypass signalling, and complete AR independence, presenting new challenges for long-term disease control.	26563462
GIMR	2020-07-03	FL	R2	TP53	Oncogenic mutations	Solid tumours; Liquid cancers	MDM2 inhibitor; SAR405838	Preclinical and clinical studies. Emergence of TP53 mutations is a resistance mechanism to HDM2 inhibition.	31310659, 27576846
GIMR	2025-02-05	FL	R2	TP53BP1	Oncogenic mutations	Breast cancer	Olaparib	Case series. Longitudinal profiling of ctDNA from 47 metastatic BRCA1/2-mutant breast cancer patients treated with HRD-targeted therapy identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1, and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.	38244928
GIMR	2020-11-15	FL	R2	TSC1	Oncogenic mutations	Urothelial carcinoma	Buparlisib	Phase 2. N=19. Buparlisib had modest activity in patients with metastatic UC whose tumors harbored TSC1 loss of function alterations (6 SD and one PR at 8 weeks on therapy).	32767682
GIMR	2021-08-04	FL	R2	Tumour Mutational Burden	High	High-grade gliomas; Anaplastic astrocytoma; Glioblastoma	Anti-PD-1 monoclonal antibody; Anti-PD-L1 monoclonal antibody	A case-control series showed no response to PD-L1 blockade in 11 HGG patients with hypermutant and mismatch repair-deficient HGG. High TMB is associated with few clonal neoantigens and no immunogenic responses in glioma populations.	32322066
GIMR	2025-01-12	FL	R2	Tumour Mutational Burden+Microsatellite Instability	Tumour Mutational Burden:High and NOT Microsatellite instability:high	Prostate cancer	Ipilimumab + Nivolumab	Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB.	39293514
GIMR	2025-01-12	FL	R2	Tumour Mutational Burden+Mismatch repair	Tumour Mutational Burden:High and NOT Mismatch repair:deficient	Prostate cancer	Ipilimumab + Nivolumab	Phase 2 INSPIRE trial. NCT04717154. N=69. Ipilimumab + nivolumab showed DCR 6 months of 38% in molecularly selected mCRPC patients. In the high TMB group without MSI-H/dMMR, the ORR was 0 (0/8), with DCS at 25%. PFS was 3.8 months. The TMB cutoff was 7.1 mut/MB.	39293514
GIMR	2025-06-21	FL	R2	U2AF1	S34F, Q157R 	Acute myeloid leukaemia	Idarubicin + Cytarabine	Preclinical study. U2AF1 mutations in AML confer resistance to idarubicin and cytarabine by mis-splicing mRNA translation genes and activating the integrated stress response (ISR). Targeting this pathway with ISRIB resensitizes U2AF1 mutant cells to chemotherapy.	38417135
GIMR	2020-11-26	FL	R2	WT1	Loss-of-function mutations	Chronic myelogenous leukaemia	Imatinib; Nilotinib; Dasatinib; Bosutinib; Ponatinib	Haploid genetic screens of gene knockouts that promoting BCR-ABL inhibitor resistance	30442766
GIMR	2021-06-08	FL	R2	XPO1	C528S	Chronic myelogenous leukaemia; Acute lymphoblastic leukaemia; Acute promyelocytic leukaemia	Selinexor	Preclinical study. Heterozygous C528S mutation in XPO1 confers similar resistance to selinexor as homozygous substitution, demonstrating a single dominant mutation is sufficient for SINE resistance.	27634897
GIMR	2026-04-02	FL	4	KRAS	G12D, G12C, G12V, G12S, G12A, G13D, V14I, L19F, Q22K, D33E, Q61H, K117N, A146V	Solid tumours	MCB-294; MCB-36	Preclinical study. MCB-294 dual-state pan-KRAS inhibitor and MCB-36 VHL-recruiting degrader demonstrated superior activity versus Bl-2865 and MRTX1133. Inhibited growth of KRAS-dependent cancer cells and patient-derived organoids. Reduced tumor progression in multiple preclinical models. Suppressed KRAS(G12C) inhibitor-resistant cancer cells.	40780213
GIMR	2026-04-02	FL	R2	KRAS	G10L, T58A, R68S	Solid tumours	MCB-294; MCB-36	Preclinical study. MCB-294 dual-state pan-KRAS inhibitor and MCB-36 VHL-recruiting degrader demonstrated superior activity versus Bl-2865 and MRTX1133. Inhibited growth of KRAS-dependent cancer cells and patient-derived organoids. Reduced tumor progression in multiple preclinical models. Suppressed KRAS(G12C) inhibitor-resistant cancer cells.	40780213
GIMR	2026-04-02	FL	3	BRCA1	Oncogenic mutations	Breast cancer; Endometrial cancer	Olaparib	Phase 2 basket trial. TAPUR. NCT02693535. N=119. Olaparib evaluated in BRCA1/2-altered solid tumors across breast (n=28), biliary tract (n=19), lung (n=25), uterine (n=15), and histology-pooled (n=32) cohorts. Primary endpoint disease control (CR/PR/SD >= 16 weeks) rates were 69%, 50%, 41%, 47%, and 41% respectively, rejecting the null 15% DC rate hypothesis for all cohorts. Signal of activity declared for all cohorts. ORR of the Breast cancer cohort was 43% (12/28). ORR of the Endometrial cancer cohort was 20% (3/15).	41100773
GIMR	2026-04-02	FL	3	BRCA2	Oncogenic mutations	Breast cancer; Endometrial cancer	Olaparib	Phase 2 basket trial. TAPUR. NCT02693535. N=119. Olaparib evaluated in BRCA1/2-altered solid tumors across breast (n=28), biliary tract (n=19), lung (n=25), uterine (n=15), and histology-pooled (n=32) cohorts. Primary endpoint disease control (CR/PR/SD >= 16 weeks) rates were 69%, 50%, 41%, 47%, and 41% respectively, rejecting the null 15% DC rate hypothesis for all cohorts. Signal of activity declared for all cohorts. ORR of the Breast cancer cohort was 43% (12/28). ORR of the Endometrial cancer cohort was 20% (3/15).	41100773
GIMR	2026-04-02	FL	4	BRCA1	Oncogenic mutations	Biliary tract cancer; Non-small cell lung cancer; Small cell lung cancer; Sweat gland carcinoma; Gastric cancer	Olaparib	Phase 2 basket trial. TAPUR. NCT02693535. N=119. Olaparib evaluated in BRCA1/2-altered solid tumors across breast (n=28), biliary tract (n=19), lung (n=25), uterine (n=15), and histology-pooled (n=32) cohorts. Primary endpoint disease control (CR/PR/SD >= 16 weeks) rates were 69%, 50%, 41%, 47%, and 41% respectively, rejecting the null 15% DC rate hypothesis for all cohorts. Signal of activity declared for all cohorts. ORR of Biliary tract cancer was (2/19) 10% (0/6 gallbladder carcinoma). ORR for NSCLC is 2/17 (12%) and one (of 2) responder in SCLC. Responders seen in solid tumour cohort: sweat gland carcinoma, and gastric cancer	41100773
GIMR	2026-04-02	FL	4	BRCA2	Oncogenic mutations	Biliary tract cancer; Non-small cell lung cancer; Small cell lung cancer; Gastric cancer; Ureteric carcinoma; Sarcoma; Oesophageal carcinoma; Duodenal adenocarcinoma; Neuroendocrine  carcinoma; Solid tumours	Olaparib	Phase 2 basket trial. TAPUR. NCT02693535. N=119. Olaparib evaluated in BRCA1/2-altered solid tumors across breast (n=28), biliary tract (n=19), lung (n=25), uterine (n=15), and histology-pooled (n=32) cohorts. Primary endpoint disease control (CR/PR/SD >= 16 weeks) rates were 69%, 50%, 41%, 47%, and 41% respectively, rejecting the null 15% DC rate hypothesis for all cohorts. Signal of activity declared for all cohorts. ORR of Biliary tract cancer was (2/19) 10%. (0/6 gallbladder carcinoma). ORR for NSCLC is 2/17 (12%) and one (of 2) responder in SCLC. Responders seen in solid tumour cohort: gastric cancer, ureteric carcinoma, Sarcoma, Oesophageal carcinoma, Duodenal carcinoma, Neuroendocrine  carcinoma	41100773
GIMR	2026-04-02	FL	2	PTEN	Loss of protein expression	Prostate cancer	Capivasertib + Abiraterone	Phase 3 CAPItello-281 trial. NCT04493853. N=1012. In PTEN-deficient metastatic hormone-sensitive prostate cancer, capivasertib plus abiraterone improved rPFS versus placebo plus abiraterone (median 33.2 versus 25.7 months; HR 0.81, 95% CI 0.66-0.98, P = 0.034). OS HR was 0.90 (95% CI 0.71-1.15, P = 0.401) at 26.4% maturity. Post hoc rPFS analyses for PTEN loss cut-offs ≥95%, ≥99%, and 100% showed consistent treatment arm performance with numerically improved treatment effect as cut-off increased.	41120017
GIMR	2026-04-02	FL	3	FGFR2	FGFR2b Overexpression, FGFR2-IIIb Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Bemarituzumab + mFOLFOX6	Phase 2. FIGHT. NCT03694522. N=155. Bemarituzumab plus mFOLFOX6 median PFS 9.5 months versus placebo 7.4 months (HR 0.68; p=0.073) in FGFR2b-selected gastric or gastro-oesophageal junction adenocarcinoma. Primary endpoint not statistically significant but promising clinical efficacy observed. Confirmatory phase 3 trials planned.	36244398
GIMR	2026-04-02	FL	3	FGFR2	FGFR2b Overexpression, FGFR2-IIIb Overexpression	Gastric cancer; Gastroesophageal junction adenocarcinoma	Bemarituzumab + mFOLFOX6	Phase 3. FORTITUDE-101. NCT05052801. N=547. In FGFR2b ≥10% advanced Gastric and gastroesophageal cancer (Bemarituzumab n=159, Placebo n=165), bemarituzumab + mFOLFOX6 improved median OS vs placebo + mFOLFOX6 (17.9 vs 12.5 months; HR 0.61, P=0.005) at primary analysis. Median PFS 8.6 vs 6.7 months (HR 0.71, P=0.019). Follow-up analysis median OS 14.5 vs 13.2 months (HR 0.82).	10.1016/j.annonc.2025.09.092
GIMR	2026-04-02	FL	4	FGFR2	FGFR2b Protein expression, FGFR2-IIIb Protein expression, FGFR2b Overexpression, FGFR2-IIIb Overexpression, FGFR2b Amplification, FGFR2-IIIb Amplification	Solid tumours; Gastric Cancer	BG-C137	Preclinical study. BG-C137. FGFR2b-targeting ADC with topoisomerase inhibitor payload. In vitro and in vivo FGFR2b-expressing tumor models. Single dose showed strong anti-tumor efficacy in FGFR2b-amplified and non-amplified PDX models with strong bystander killing effect in vitro in heterogeneous FGFR2b expression models.	10.1158/1538-7445.AM2025-3778