History of database changes

05 May, 2025 (Version: 20250505AU) (Latest version)

New Trametinib in Juvenile myelomonocytic leukaemia with CBL Y371H, C384R: 3

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. References: 38867349

New Trametinib in Juvenile myelomonocytic leukaemia with KRAS A146T, G13D: 3

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. References: 38867349

New Trametinib in Juvenile myelomonocytic leukaemia with NRAS Q61L, G12S: 3

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. References: 38867349

New Trametinib in Juvenile myelomonocytic leukaemia with PTPN11 E76V, D61V: 3

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. References: 38867349

04 May, 2025 (Version: 20250504AU)

New D3S-001 in Non-small cell lung cancer with KRAS G12C: 4

Preclinical study. D3S-001, a GDP-bound KRAS G12C inhibitor with rapid target engagement kinetics, showed robust antitumor activity preclinically and promising clinical efficacy. References: 38717075

Changed Dasatinib in Acute lymphoblastic leukaemia, Chronic myelogenous leukaemia with ABL1 E255K, E255V, F359C, F359I, F359V, Y253H, A337V, P465S: 2

Comments changed: Requires presence of the BCR-ABL fusion transcript by PCR in either peripheral blood or bone marrow., and not TGA approved by biomarker. OncoKB LOE 1.. (First curated: 2020-05-21)

Changed Lorlatinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: 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, F1174LG1202R, I1171N, I1171S, I1171T, L1196M, L1196Q, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L. (First curated: 2025-04-30)

Changed Crizotinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: 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, F1174LG1202R, 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, — G1202R compound mutant, I1171N and D1203N, F1174L. (First curated: 2025-04-30)

Changed Ceritinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: 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, F1174LG1202R, T1151insT, C1156Y, I1171N, I1171S, I1171T, L1196Q, G1202del, D1203N, E1210K, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L. (First curated: 2025-04-30)

Changed Brigatinib in Solid tumours, Non-small cell lung cancer with ALK : R2

Alterations changed: 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, F1174LG1202R, 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, — G1202R compound mutant, I1171N and D1203N, F1174L. (First curated: 2025-04-30)

30 April, 2025 (Version: 20250430AU)

New Ensartinib in Solid tumours, Non-small cell lung cancer with ALK C1156Y, I1171N, V1180L, L1196Q, L1198F, D1203N, S1206F, S1206Y, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New Zotizalkib in Solid tumours, Non-small cell lung cancer with 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: 4

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. References: 39269178

New NVL-655 in Solid tumours, Non-small cell lung cancer with 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, — G1202R compound mutant, I1171N and L1198F, F1174L, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New Alectinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, C1156Y, F1174L, D1203N, S1206F, S1206Y, E1210K, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New Ceritinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, F1174L, V1180L, L1196M, L1196Q, S1206F, S1206Y, G1269A, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New Crizotinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, F1174L, V1180L, L1198F, G1202del, I1171N and L1198F, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New Brigatinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, I1171S, I1171T, F1174L, V1180L, L1196M, L1196Q, G1269A, I1171N and L1198F, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New Lorlatinib in Solid tumours, Non-small cell lung cancer with ALK T1151M, T1151insT, C1156Y, F1174L, V1180L, L1196Q, L1198F, G1202del, D1203N, S1206F, S1206Y, E1210K, G1269A, F1174L, Exon 2–3 deletion, Exon 2-17 deletion: 4

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. References: 39269178

New AMG-193 in Solid tumours with MTAP Deletion: 4

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.". References: 39282709

New Lorlatinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, I1171N, I1171S, I1171T, L1196M, L1196Q, G1202R and T1151M, G1202R and F1174L, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L: R2

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. References: 39269178

New Crizotinib in Solid tumours, Non-small cell lung cancer with 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, — G1202R compound mutant, I1171N and D1203N, F1174L: R2

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. References: 39269178

New Ceritinib in Solid tumours, Non-small cell lung cancer with 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, — G1202R compound mutant, I1171N and L1198F, I1171N and D1203N, F1174L: R2

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. References: 39269178

New Brigatinib in Solid tumours, Non-small cell lung cancer with 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, — G1202R compound mutant, I1171N and D1203N, F1174L: R2

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. References: 39269178

New Alectinib in Solid tumours, Non-small cell lung cancer with 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: R2

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. References: 39269178

New Ensartinib in Solid tumours, Non-small cell lung cancer with ALK G1202R, T1151insT, I1171S, I1171T, L1196Q, G1202del, E1210K, G1269A, G1202R and L1196M, G1202R and L1198F, G1202R and G1269A, I1171N and D1203N: R2

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. References: 39269178

New NVL-655 in Solid tumours, Non-small cell lung cancer with ALK I1171N and D1203N: R2

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. References: 39269178

New Zotizalkib in Solid tumours, Non-small cell lung cancer with ALK T1151insT, I1171N, I1171S, I1171T, V1180L, D1203N, I1171N and D1203N: R2

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. References: 39269178

New Zongertinib in Cholangiocarcinoma with NRG1 SDC4-NRG1 fusion: 4

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. References: 39248702

New Zongertinib in Breast cancer with ERBB2 V777L, Amplification, D769H, A775_Y776insYVMA, G776delinsVC, Exon 20 insertion, L755A, L755M, L755P, L755S, S310A, S310F, S310Y, V777L, V777M, V842I: 4

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. References: 39248702

New Zongertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, T790M: R2

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. References: 39248702

28 April, 2025 (Version: 20250428AU)

New BBO-8520 in Solid tumours with KRAS G12C: 4

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. References: 39642212

Changed Therapy in Solid tumour with BRCA1 Oncogenic mutations: 4

Therapy changed: PalacaparibAZD9574. (First curated: 2023-10-25)

Changed Therapy in Solid tumour with BRCA2 Oncogenic mutations: 4

Therapy changed: PalacaparibAZD9574. (First curated: 2023-10-25)

27 April, 2025 (Version: 20250427AU)

New HRS-4642 in Solid tumours, Non-small cell lung cancer with KRAS G12D: 4

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. References: 38942026

25 April, 2025 (Version: 20250425AU)

New FHD-609 in Solid tumours with SMARCB1 Oncogenic mutations: 4

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. References: 39660994

New BI-7273 in Synovial sarcoma with SS18 SS18-SSX fusion: 4

Preclinical study. BRD9 inhibition selectively targets and degrades the protein in synovial sarcoma, reversing oncogenic gene expression and demonstrating potent anti-tumor activity. References: 39660994

New FHD-609 in Synovial sarcoma with SS18 SS18-SSX fusion: 4

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. References: 39660994

New FHD-609, FHD-286 in Small-cell lung cancer with POU2F3 Protein expression: 4

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. References: 39029464

24 April, 2025 (Version: 20250424AU)

Changed Amivantamab in Non-small cell lung cancer with EGFR Exon 20 insertion: 1B

Tier changed: 1B2. Comments changed: TGA approved. Not PBS Listed. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months.Not TGA approved. FDA accelerated approval 2021-05-21. Phase 1 CHRYSALIS trial. ORR 40%, including 3 CR. Median DOR 11.1 months. Median PFS 8.3 months.. (First curated: 2021-05-22)

Changed Amivantamab + Carboplatin + Pemetrexed in Non-small cell lung cancer with EGFR Exon 20 insertion: 1B

Tier changed: 1B2. Comments changed: 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.Not TGA approved. 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.. (First curated: 2023-10-29)

Changed Amivantamab in Non-small cell lung cancer with EGFR C797S, Exon 20 insertion: 3

Tier changed: 32. Comments changed: 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.. (First curated: 2020-06-28)

Changed Poziotinib in Non-small cell lung cancer with EGFR S768I, A767_V769dup, P772dupDNP, S768_D770dup, D770insG, D770insY, H773Y, N771insH, D770delinsGY: 3

Comments changed: 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.. (First curated: 2020-04-16)

Changed Amivantamab + Lazertinib in Non-small cell lung cancer with 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: 3

Comments changed: 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).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.. (First curated: 2021-06-10)

Changed Osimertinib + Savolitinib in Non-small cell lung cancer with EGFR+MET EGFR:Oncogenic mutations and MET:amplification: 3

Comments changed: 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).Phase 1B TATTON. Significant ORR. (First curated: 2020-06-23)

Changed Capmatinib + Gefitinib in Non-small cell lung cancer with EGFR+MET MET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R: 3

Comments changed: 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.. (First curated: 2020-05-05)

Changed Tepotinib + Gefitinib in Non-small cell lung cancer with EGFR+MET MET:amplification and EGFR:exon 19 deletion, MET:amplification and EGFR:L858R: 3

Comments changed: 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).. (First curated: 2020-06-11)

Changed Nilotinib in Gastrointestinal stromal tumour with KIT Oncogenic mutations; Exon 11 mutation; Exon 9 mutation: 3

Comments changed: 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.DCR 29% third line. (First curated: 2020-05-07)

Changed Trametinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: 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]METRIC subgroup. References changed: 3527208422663011. (First curated: 2025-04-242020-06-11)

23 April, 2025 (Version: 20250423AU)

New GV1001 + Gemcitabine + Capecitabine in Pancreatic adenocarcinoma with CCL11 Serum level high: 2

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. References: 37903909

New Cadonilimab + Anlotinib in Non-small cell lung cancer with CD274 Protein expression: 3

Phase Ib/II trial. NCT04646330. N=69. Cadonilimab and anlotinib demonstrated manageable safety and promising efficacy 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. References: 38110665

New Ponatinib + Asciminib in Chronic myelogenous leukaemia with ABL1 BCR-ABL1 fusion AND T315I AND E355G: 4

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. References: 39214096

New G007-LK, RK-582 in Colorectal adenocarcinoma with APC+PIK3CA APC:Oncogenic mutations AND PIK3CA:Oncogenic mutations: 4

Preclinical study. Tankyrase inhibitor sensitivity in colorectal cancer cells correlates with APC/PIK3CA mutations and beta-catenin status, suggesting potential predictive biomarkers. References: 37968472

New ADCT-701 in Neuroblastoma with DLK1 Protein expression: 4

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. References: 39454577

New Abemaciclib + AZD8421 in Breast cancer with ESR1+TP53 ESR1:Protein expression AND TP53:Oncogenic mutations: 4

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. References: 39532066

New Ribociclib, BSJ-03-123 in Diffuse hemispheric glioma with H3F3A G34R, G34V: 4

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. References: 39232581

New ABBV-400 in Colorectal adenocarcinoma with MET Protein expression; Overexpression: 4

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. References: 10.1200/JCO.2024.42.16_suppl.3515

New Olaparib in Prostate cancer with BRCA2 Reversion mutations: R2

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. References: 39577422

New Abemaciclib, Palbociclib, Ribociclib in Breast cancer with ESR1+MDM2 ESR1:Protein expression AND MDM2:Amplification: R2

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. References: 39532066

New Abemaciclib, Palbociclib, Ribociclib in Breast cancer with ESR1+TP53 ESR1:Protein expression AND TP53:Oncogenic mutations: R2

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. References: 39532066

New FOLFOX + Bevacizumab + Durvalumab + Oleclumab in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Phase 1B/2. COLUMBIA-1. NCT04068610. N=59. Durvalumab + oleclumab added to FOLFOX and bevacizumab did not significantly improve ORR (61.5% vs 46.2%) in metastatic microsatellite-stable colorectal cancer. References: 39048638

New Olaparib in Prostate cancer with PALB2 Reversion mutations: R2

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. References: 39577422

Changed Pamiparib + AZD7762 with H3F3A G34R, G34V: 4

Cancer type(s) changed: Diffuse hemispheric gliomaHigh-grade gliomas (First curated: 2023-07-24)

Changed eFT508 with MYD88 Gain-of-function mutations: 4

Cancer type(s) changed: Diffuse large B-cell lymphomaSolid tumours (First curated: 2020-04-16)

Changed Osimertinib in Non-small cell lung cancer with EGFR C797S, C797G: R2

References changed: 25964297; 30073261; 37938348. (First curated: 2020-04-16)

Changed Pazopanib in Gastrointestinal stromal tumour with KIT D816V, Y823D: R2

References changed: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2009/022465s000_PharmR.pdfOther. (First curated: 2025-04-21)

Changed Osimertinib in Non-small cell lung cancer with MET Amplification: R2

Comments changed: Secondary resistance post Osimertinib. MET amplification determined by FISH, liquid biopsy.Secondary resistance post Osimertinib. Amplification determined by FISH.. References changed: 27252416; 37938348. (First curated: 2020-03-12)

Changed Selinexor in Chronic myelogenous leukaemia, Acute lymphoblastic leukaemia, Acute promyelocytic leukaemia with XPO1 C528S: R2

(First curated: 2025-04-232021-06-08)

21 April, 2025 (Version: 20250421AU)

New Pazopanib in Gastrointestinal stromal tumour with KIT D816V, Y823D: R2

AccessFDA data. GW786034B: weak activity against V654A mutant (IC50=1.45 uM); inactive against D816V (IC50 >10 uM) and Y823D (IC50 >5 uM) mutations. References: Other

14 April, 2025 (Version: 20250414AU)

New Olaparib in Uterine serous carcinoma with BRIP1 Oncogenic mutations, Q554Hfs*35: 4

Case report. Olaparib monotherapy resulted in a complete response lasting over nine months in a patient with BRIP1-mutated high-grade serous endometrial cancer. References: 32923896

New VX-970 in Adenoid cystic carcinoma with MYB Overexpression; MYB-NFIB fusion: 4

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. References: 32001675

13 April, 2025 (Version: 20250413AU)

New Sacituzumab Govitecan in Breast cancer with TACSTD2 T256R: R2

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. References: 34404686

New Sacituzumab Govitecan in Breast cancer with TOP1 E418K: R2

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. References: 34404686

10 April, 2025 (Version: 20250410AU)

Changed Therapy in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 1

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-06-05)

Changed Therapy in Breast cancer with ERBB2 Amplification, Overexpression: 1B

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-09-20)

Changed Therapy in Breast cancer with ERBB2 Amplification; Overexpression: 1B

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-05-12)

Changed Tovorafenib in Low-grade gliomas with BRAF V600, V600E, KIAA1549-BRAF fusion,Fusion: 2

Tier changed: 23. Comments changed: 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.. (First curated: 2024-04-26)

Changed Neratinib + Capecitabine in Breast cancer with ERBB2 Amplification: 2

Comments changed: 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.Not TGA approved. FDA approved. NALA: Phase III trial in patient previously treated with two or more lines of HER2-directed regimens, median PFS of neratinib was superior over lapatinib.. (First curated: 2020-05-17)

Changed Trastuzumab deruxtecan in Biliary tract cancer with ERBB2 Overexpression: 2

Tier changed: 23. Comments changed: 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.Phase 2. NCT04482309. DESTINY-PanTumor02. ORR in biliary. (First curated: 2023-06-20)

Changed Therapy in Colorectal cancer with ERBB2 Overexpression: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2024-08-29)

Changed Therapy in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-01-15)

Changed Trastuzumab deruxtecan in Cervical cancer, Endometrial cancer, Ovarian cancer, Bladder cancer, Solid tumours except Pancreatic adenocarcinoma, Biliary tract cancers with ERBB2 Overexpression, Protein expression: 2

Tier changed: 23. Comments changed: 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.. (First curated: 2023-06-20)

Changed Therapy in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2 Overexpression, Protein expression AND Amplification: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-09-20)

Changed Therapy in Non-small cell lung cancer with ERBB2 S310F, S310Y, L755S, L755P, A769H, A775_G776insYVMA, A775_G776insTVMA, G776S, G776delinsVC, V777L, P780_Y781insGSP, G778_S779insLPS, Exon 20 insertion, Exon 20 mutation: 2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-09-19)

Changed Pemigatinib in Myelodysplastic/myeloproliferative diseases, Myeloproliferative diseases, Acute lymphoblastic leukaemia, Acute myeloid leukaemia with FGFR1 Rearrangement, Fusion: 2

Comments changed: 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.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 in the marrow. 22 of 28 patients (79%) achieved complete cytogenetic response.. (First curated: 2022-08-31)

Changed Infigratinib in Cholangiocarcinoma with FGFR2 Fusions: 2

Comments changed: 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.Not TGA approved. FDA accelerated approved for use in second-line and beyond. Phase II study (NCT02150967) with N=108. ORR: 23%. Median PFS 7.3 months.. (First curated: 2020-06-11)

Changed Cobimetinib, Trametinib in Histiocytosis with MAP2K1 P142L, P124Q, Q56P, P105_107del: 2

Comments changed: Phase 2 Umbrella studyPhase II Umbrella study. (First curated: 2020-04-16)

Changed Taselisib + Fulvestrant in Breast cancer with PIK3CA Oncogenic mutations: 2

Comments changed: 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.Not TGA approved. Not FDA approved. Positive Phase III 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.. (First curated: 2020-06-23)

Changed Vemurafenib + Cobimetinib in Papillary craniopharyngioma with BRAF V600E: 3

Comments changed: Phase 2 Alliance A071601. NCT03224767. Objective response in 15 of 16 patients.Phase II Alliance A071601. NCT03224767. Objective response in 15 of 16 patients.. (First curated: 2021-06-04)

Changed Ceralasertib + Olaparib in Ovarian cancer with BRCA1 Oncogenic mutations, Oncogenic mutations (germline): 3

Comments changed: Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 50% (6/12).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 50% (6/12).. (First curated: 2021-06-28)

Changed Ceralasertib + Olaparib in Ovarian cancer with BRCA2 Oncogenic mutations, Oncogenic mutations (germline): 3

Comments changed: Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).. (First curated: 2021-06-28)

Changed Odronextamab in Follicular lymphoma with CD20 Protein expression: 3

Comments changed: 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.Phase II 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.. (First curated: 2025-02-16)

Changed Durvalumab in Urothelial carcinoma with CD274 Protein expression: 3

Comments changed: 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.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 III DANUBE trial results.. (First curated: 2020-06-29)

Changed Osimertinib in Non-small cell lung cancer with EGFR G719, L747S, S768I, L861Q: 3

Comments changed: Phase 2 KCSG-LU15-09: Osimertinib for Patients With NSCLC harboring uncommon EGFR Mutations. N=37, ORR 50%Phase II KCSG-LU15-09: Osimertinib for Patients With NSCLC harboring uncommon EGFR Mutations. N=37, ORR 50%. (First curated: 2021-06-01)

Changed Poziotinib in Solid tumours, Non-small cell lung cancer with ERBB2 A775_G776insYVMA, G778_P780dup: 3

Comments changed: Phase 2. ORR 43% (5/12) and DCR 83%. NCT03066206.Phase II. ORR 43% (5/12) and DCR 83%. NCT03066206.. (First curated: 2020-06-15)

Changed Therapy in Biliary tract cancer with ERBB2 Amplification, Overexpression: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-06-06)

Changed Dacomitinib in Non-small cell lung cancer with ERBB2 G778_P780dup: 3

Comments changed: Phase 2 trial: 2/2 patients harbouring the mutation responded to Dacomitinib with prolonged response.Phase II trial: 2/2 patients harbouring the mutation responded to Dacomitinib with prolonged response.. (First curated: 2021-03-08)

Changed Therapy in Non-small cell lung cancer with ERBB2 Kinase domain mutation: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-05-31)

Changed BAY 2927088 in Non-small cell lung cancer with ERBB2 Oncogenic mutations: 3

Comments changed: Phase 1/2 SOHO-01 study. NCT05099172. N=34. BAY 2927088 led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months.Phase I/II SOHO-01 study. NCT05099172. N=34. BAY 2927088 led to ORR of 70% (23/33) and DCR of 82% in HER2-mutant NSCLC patients. Median PFS was 8.1 months.. (First curated: 2024-07-03)

Changed IMU-131 in Solid tumours with ERBB2 Overexpression, Protein expression, Amplification: 3

Comments changed: Phase 1b Trial IMU.ACS.001. NCT02795988. Objective response seen in 5 of 14 patients.Phase Ib Trial IMU.ACS.001. NCT02795988. Objective response seen in 5 of 14 patients.. (First curated: 2023-01-20)

Changed Therapy in Non-small cell lung cancer with ERBB2 Protein expression AND NOT Oncogenic mutations, Overexpression AND NOT Oncogenic mutations: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2024-05-14)

Changed Therapy in Solid tumours with ERBB2 S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, A775_G776insYVMA, L755S, P780_Y781insGSP, T862A, V842I: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2024-05-08)

Changed Therapy in Colorectal adenocarcinoma with 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: 3

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-05-30)

Changed Camizestrant in Breast cancer with ESR1 E380Q, S463P, V422del, L536P, L536H, Y537C, Y537D, Y537N, Y537S, D538G: 3

Comments changed: 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).Phase I. 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).. (First curated: 2021-06-08)

Changed Elacestrant in Breast cancer with ESR1 Protein expression: 3

Comments changed: Phase 1. N=50 with ORR 19%. 52% treated with prior SERD.Phase I. N=50 with ORR 19%. 52% treated with prior SERD.. (First curated: 2021-02-02)

Changed Camizestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Comments changed: 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).Phase I. 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).. (First curated: 2021-06-08)

Changed Imlunestrant in Breast cancer with 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: 3

Comments changed: 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).Phase Ia/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).. (First curated: 2024-09-09)

Changed Ceralasertib + Olaparib in Ovarian cancer with Homologous Recombination Deficiency Score High: 3

Comments changed: Phase 2. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).Phase II. CAPRI. Cohort C. NCT03462342. Combination of olaparib and ceralasertib in patients with acquired PARP resistance. ORR: 46% (6/13).. (First curated: 2021-06-28)

Changed Tipifarnib in Head and neck squamous cell carcinoma , Salivary gland cancers, Urothelial carcinoma with HRAS Oncogenic mutations: 3

Comments changed: Single arm Phase 2 of Tipifarnib in R/M HNSCC patients. ORR 55%. mPFS tipifarnib: 5.6 months. KO-TIP-001Single arm Phase II of Tipifarnib in R/M HNSCC patients. ORR 55%. mPFS tipifarnib: 5.6 months. KO-TIP-001. (First curated: 2020-05-31)

Changed Olaparib in Chondrosarcoma with IDH1 R132C, R132S, R132: 3

Comments changed: 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.Phase II 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.. (First curated: 2021-03-19)

Changed Olaparib in Epithelioid haemangioendothelioma with IDH2 V305M: 3

Comments changed: 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.Phase II 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.. (First curated: 2021-03-19)

Changed Nilotinib in Melanoma with KIT Exon 11 mutation, Exon 11 deletion, L576P, K642E, I817L, V559A: 3

Comments changed: Phase 2 UN10-06 trial. Exon 11 mutation ORR 29%. One responder I817L.Phase II UN10-06 trial. Exon 11 mutation ORR 29%. One responder I817L.. (First curated: 2020-12-31)

Changed Garsorasib in Colorectal adenocarcinoma with KRAS G12C: 3

Comments changed: 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%.Phase I/II (NCT04585035). N=24. D-1553 demonstrated a activity in heavily pretreated CRC with KRAS G12C mutations. Confirmed ORR was 21%. DCR was 96%.. (First curated: 2023-12-17)

Changed Tepotinib in Non-small cell lung cancer with MET Amplification: 3

Comments changed: 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%.Phase II 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%.. (First curated: 2021-06-28)

Changed Temozolomide + Ipilimumab + Nivolumab in Colorectal adenocarcinoma with MGMT Loss of protein expression, Promoter methylation: 3

Comments changed: 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.Phase II 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.. (First curated: 2022-03-23)

Changed Ipilimumab + Nivolumab in Prostate cancer with Microsatellite Instability High: 3

Comments changed: 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.Phase II 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.. (First curated: 2025-01-12)

Changed Ipilimumab + Nivolumab in Prostate cancer with Mismatch repair Deficient: 3

Comments changed: 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.Phase II 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.. (First curated: 2025-01-12)

Changed Mirdametinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

Comments changed: 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.NF106. Phase II trial. N=19. NCT02096471. ORR 42%; CBR 95% with significant durable decreases in pain ratings in patients with NF1-related plexiform neurofibromas.. (First curated: 2021-02-02)

Changed Cobimetinib in Histiocytosis with NRAS Oncogenic mutations: 3

Comments changed: Phase 2 Umbrella studyPhase II Umbrella study. (First curated: 2020-04-16)

Changed Binimetinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: Not TGA approved. Positive Phase 3 NEMO result, but overall small absolute PFS gain. FDA application withdrawn and NCCN 2B. Revised Tier 3Not TGA approved. Positive Phase III NEMO result, but overall small absolute PFS gain. FDA application withdrawn and NCCN 2B. Revised Tier 3. (First curated: 2020-10-13)

Changed Binimetinib in Melanoma with NRAS Oncogenic mutations: 3

Comments changed: Phase 2. Small sample sizePhase II. Small sample size. (First curated: 2020-06-11)

Changed KL590586 in Solid tumour with RET Fusions, Oncogenic mutations: 3

Comments changed: 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%.Phase I 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%.. (First curated: 2023-11-20)

Changed Adavosertib in Uterine serous carcinoma with TP53 Oncogenic mutations: 3

Comments changed: 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.Single arm phase II 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.. (First curated: 2021-03-31)

Changed Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA1 Oncogenic mutations: 4

Comments changed: 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.Phase Ib. 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.. (First curated: 2025-02-16)

Changed Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA2 Oncogenic mutations: 4

Comments changed: 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.Phase Ib. 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.. (First curated: 2025-02-16)

Changed Atezolizumab + Carboplatin + Paclitaxel + Bevacizumab in Ovarian cancer with CD274 Protein expression: 4

Comments changed: 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).IMagyn050/GOG3015/ENGOT-OV39: Phase III 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).. (First curated: 2021-05-18)

Changed Dacomitinib in Glioblastoma with EGFR Amplification AND G598V: 4

Comments changed: 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).Phase II: Dacomitinib was not effecitive in EGFR-amplified GBM (5/30 patients in arm B achieved PFS6 and did not meet the primary endpoint).. (First curated: 2021-05-11)

Changed E-EDV-D682 in Pancreatic adenocarcinoma with EGFR Protein expression, Overexpression: 4

Comments changed: Interim data from Phase 1/2 ACTRN12619000385145. N=9. Confirmed response at 4 months in 4 of 5 patients. CBR 8 weeks 89%.Interim data from Phase I/II ACTRN12619000385145. N=9. Confirmed response at 4 months in 4 of 5 patients. CBR 8 weeks 89%.. (First curated: 2022-03-03)

Changed Therapy in Gastric cancer, Gastroesophageal junction adenocarcinoma, Colorectal adenocarcinoma with ERBB2 Amplification; Alteration: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-05-31)

Changed Therapy in Non-small cell lung cancer with ERBB2 Overexpression, Amplification: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-05-31)

Changed Therapy in Breast cancer with ERBB2 protein expression and NOT amplification: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2020-10-05)

Changed Therapy in Biliary tract cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 4

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-06-06)

Changed MRG004A in Solid tumours with F3 Protein expression: 4

Comments changed: 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.Phase I/II study. N=63. MRG004A showed antitumor activity in heavily pretreated patients with solid tumors, including pancreatic cancer (ORR 33%, DCR 83%) at 2mg/kg.. (First curated: 2024-06-02)

Changed Rucaparib in Prostate cancer with FANCA Loss-of-function mutations: 4

Comments changed: Phase 2 TITRON2Phase II TITRON2. (First curated: 2020-04-16)

Changed Infigratinib in Lung squamous cell carcinoma with FGFR1 Amplification: 4

Comments changed: Responses in Phase 1 dose expansionResponses in Phase I dose expansion. (First curated: 2020-06-11)

Changed Erdafitinib in Lung squamous cell carcinoma with FGFR1 Amplification, Oncogenic mutations: 4

Comments changed: Phase 2 trial (FIND)Phase II trial (FIND). (First curated: 2020-06-11)

Changed Futibatinib in Solid tumours with FGFR1 N546D: 4

Comments changed: 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).Phase I 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).. (First curated: 2020-09-25)

Changed Erdafitinib in Lung squamous cell carcinoma with FGFR2 Oncogenic mutations: 4

Comments changed: Phase 2 trial (FIND)Phase II trial (FIND). (First curated: 2020-06-11)

Changed Erdafitinib in Lung squamous cell carcinoma with FGFR3 Amplification, Fusion, Oncogenic mutations: 4

Comments changed: Phase 2 trial (FIND)Phase II trial (FIND). (First curated: 2020-06-11)

Changed Erdafitinib in Solid tumours with FGFR3 Amplification, Fusion, Oncogenic mutations and NOT V565 and NOT V550: 4

Comments changed: NCT01703481, Phase 1 dose escalation and expansion. ORR 46% in urothelial carcinoma and 27% in cholangiocarcinoma. <10% for the rest of tumour types.NCT01703481, Phase I dose escalation and expansion. ORR 46% in urothelial carcinoma and 27% in cholangiocarcinoma. <10% for the rest of tumour types.. (First curated: 2020-06-11)

Changed Trametinib in Non-small cell lung cancer with KRAS Oncogenic mutations: 4

Comments changed: Phase 2, ORR 12% but worse PFS than docetaxelPhase II, ORR 12% but worse PFS than docetaxel. (First curated: 2020-06-18)

Changed Binimetinib in Solid tumours with KRAS Oncogenic mutations: 4

Comments changed: Phase 1, ORR 3%Phase I, ORR 3%. (First curated: 2020-04-16)

Changed Olaparib in Pancreatic adenocarcinoma with PALB2 Oncogenic mutations (germline): 4

Comments changed: 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.Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. One responder seen in PALB2 germline mutation.. (First curated: 2021-03-16)

Changed PRT3789 in Solid tumours with SMARCA4 Oncogenic mutation: 4

Comments changed: Phase 1. NCT05639751. PRT3789 selectively targets SMARCA4-deficient cells with anti-tumor activity and synergistic effects with therapies.Phase I. NCT05639751. PRT3789 selectively targets SMARCA4-deficient cells with anti-tumor activity and synergistic effects with therapies.. (First curated: 2024-08-29)

Changed PLX2853, PLX2853 + carboplatin in Ovarian Cancer with ARID1A Oncogenic mutation: R2

Comments changed: 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.Phase Ib/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.. (First curated: 2023-10-12)

Changed Olaparib in Pancreatic adenocarcinoma with ARID1A Oncogenic mutations: R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. ARID1A (N=3)Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. ARID1A (N=3). (First curated: 2021-03-16)

Changed Olaparib in Pancreatic adenocarcinoma with ATM Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: 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)Two Phase II 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). (First curated: 2021-03-16)

Changed Ipilimumab + Nivolumab in Prostate cancer with BRCA2 Oncogenic mutation: R2

Comments changed: 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.Phase II 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.. (First curated: 2025-01-12)

Changed Fulvestrant + Palbociclib in Breast cancer with CCNE1 mRNA expression: R2

Comments changed: Exploratory analysis from Phase 3 PEARL study: high tumour CCNE mRNA expression is correlated to relevanceExploratory analysis from Phase III PEARL study: high tumour CCNE mRNA expression is correlated to relevance. (First curated: 2021-06-10)

Changed Ipilimumab + Nivolumab in Prostate cancer with CDK12 Oncogenic mutation: R2

Comments changed: 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.Phase II 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.. (First curated: 2025-01-12)

Changed Dacomitinib in Glioblastoma with EGFR Amplification: R2

Comments changed: 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)Phase II: Dacomitinib was not effecitive in EGFR-amplified GBM. A subset experienced a durable, clinically meaningful benefit (2/4 G598V with TTP>=6 months). (First curated: 2021-05-11)

Changed Therapy in Colorectal adenocarcinoma with ERBB2 No protein expression, Low protein expression: R2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2021-06-08)

Changed Therapy in Colorectal cancer with ERBB2 Protein expression AND Amplification AND NOT Overexpression: R2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2024-08-29)

Changed Therapy in Colorectal cancer with ERBB2+KRAS ERBB2:Overexpression AND KRAS:Oncogenic mutation, ERBB2:Protein expression AND KRAS:Oncogenic mutation: R2

Therapy changed: Fam-trastuzumab deruxtecan-nxki. (First curated: 2024-08-29)

Changed Olaparib in Pancreatic adenocarcinoma with FANCD2 Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.. (First curated: 2021-03-16)

Changed Olaparib in Cholangiocarcinoma with IDH1 R132C, R132: R2

Comments changed: Phase 2 Basket trial. Olaparib for IDH mutations. No responders in four cholangiocarcinoma cases (3 cases with R132C).Phase II Basket trial. Olaparib for IDH mutations. No responders in four cholangiocarcinoma cases (3 cases with R132C).. (First curated: 2021-03-19)

Changed Nilotinib in Melanoma with KIT Amplification: R2

Comments changed: Phase 2 UN10-06 trial. In KIT amplification only subgroup, only 1/15 response with with DOR of 5 weeks only (ORR 6%). Gene co-mutation status was not available in the case.Phase II UN10-06 trial. In KIT amplification only subgroup, only 1/15 response with with DOR of 5 weeks only (ORR 6%). Gene co-mutation status was not available in the case.. (First curated: 2020-12-31)

Changed Nilotinib in Melanoma with KIT Exon 13 mutation: R2

Comments changed: Phase 2 UN10-06 trial. In KIT exon 13 mutation subgroup, 0/15 response. Gene co-mutation status was not available in the case.Phase II UN10-06 trial. In KIT exon 13 mutation subgroup, 0/15 response. Gene co-mutation status was not available in the case.. (First curated: 2020-12-31)

Changed Imatinib in Adenoid cystic carcinoma with KIT Overexpression: R2

Comments changed: Phase 2 consortium-based study. N=15. ORR 0%.Phase II consortium-based study. N=15. ORR 0%.. (First curated: 2020-12-31)

Changed Afatinib in Colorectal adenocarcinoma with KRAS Oncogenic mutations: R2

Comments changed: Randomised Phase 2 trial. No activities is seen in Afatinib arm (ORR 0%, of 36) in KRAS mutant group.Randomised phase II trial. No activities is seen in Afatinib arm (ORR 0%, of 36) in KRAS mutant group.. (First curated: 2022-04-04)

Changed Olaratumab + Doxorubicin in Soft tissue sarcomas with PDGFRA Overexpression: R2

Comments changed: ANNOUNCE trial. Negative Phase 3. No benefit over doxorubicin in PDGFRA overexpression subgroup.ANNOUNCE trial. Negative Phase III. No benefit over doxorubicin in PDGFRA overexpression subgroup.. (First curated: 2020-06-30)

Changed Everolimus in Solid tumours with PIK3CA Amplification, Oncogenic mutations: R2

Comments changed: Phase 2 Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.Phase II Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.. (First curated: 2021-06-02)

Changed Everolimus in Solid tumours with PTEN Loss of protein expression, Loss-of-function mutations: R2

Comments changed: Phase 2 Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.Phase II Basket trial. Everolimus in PIK3CA amplification and oncogenic mutation. ORR 0%. PFS 1.6 months.. (First curated: 2021-06-02)

Changed Olaparib in Pancreatic adenocarcinoma with PTEN Oncogenic mutations: R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. PTEN (N=2)Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold. PTEN (N=2). (First curated: 2021-03-16)

Changed Olaparib in Pancreatic adenocarcinoma with RAD51C Oncogenic mutations, Oncogenic mutations (germline): R2

Comments changed: Two Phase 2 studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.Two Phase II studies of Olaparib in previously treatment pancreatic cancer. ORR 4% did not meet predefined threshold.. (First curated: 2021-03-16)

Changed Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Microsatellite Instability Tumour Mutational Burden:High and NOT Microsatellite instability:high: R2

Comments changed: 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.Phase II 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.. (First curated: 2025-01-12)

Changed Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and NOT Mismatch repair:deficient: R2

Comments changed: 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.Phase II 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.. (First curated: 2025-01-12)

31 March, 2025 (Version: 20250331AU)

New Darovasertib in Uveal melanoma with GNA11 Oncogenic mutations: 4

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. References: 10.1200/JCO.2024.42.16_suppl.9510

New Crizotinib + Darovasertib, Binimetinib + Darovasertib in Solid tumours, Uveal melanoma with GNA11 Oncogenic mutations: 4

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. References: 10.1158/1538-7445.AM2021-1343

New DYP688 in Uveal melanoma with GNA11 Oncogenic mutations: 4

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. References: 10.1158/1538-8514.CANCERCHEM24-IA022

New Darovasertib in Uveal melanoma with GNAQ Oncogenic mutations: 4

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. References: 10.1200/JCO.2024.42.16_suppl.9510

New Crizotinib + Darovasertib, Binimetinib + Darovasertib in Solid tumours, Uveal melanoma with GNAQ Oncogenic mutations: 4

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. References: 10.1158/1538-7445.AM2021-1343

New DYP688 in Uveal melanoma with GNAQ Oncogenic mutations: 4

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. References: 10.1158/1538-8514.CANCERCHEM24-IA022

22 March, 2025 (Version: 20250322AU)

New Encorafenib + Cetuximab + mFOLFOX6 in Colorectal adenocarcinoma with BRAF V600E: 2

Phase 3 BREAKWATER trial. NCT04607421. Encorafenib + cetuximab + mFOLFOX6 significantly improved ORR over SOC (60.9% vs 40.0%) in previously untreated BRAF V600E-mutant metastatic colorectal cancer, with a median duration of response of 13.9 months versus 11.1 months. References: 39863775

16 March, 2025 (Version: 20250316AU)

New AZD9592 in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 4

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. References: 10.1158/1538-7445.AM2023-5736

New Everolimus + Exemestane in Breast cancer with EIF4EBP1 Protein expression: 4

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. References: 38182687

New Sotorasib + Tipifarnib in Solid tumours, Non-small cell lung cancer with KRAS G12C: 4

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. References: 38278976

New Capivasertib + Docetaxel in Prostate cancer with PTEN Loss-of-function mutations: 4

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. References: 38396173

15 March, 2025 (Version: 20250315AU)

New PF-9363 in Breast cancer with KAT6A Amplification, Overexpression: 4

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. References: 37557181

New PF-9363 in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression, ESR1:D538, ESR1:Y537: 4

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. References: 37557181

07 March, 2025 (Version: 20250307AU)

New Cabozantinib in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 3

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%. References: 33442015

New Avutometinib + BI-3406 in Melanoma with NF1 Oncogenic mutations: 4

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. References: 39488215

New Abemaciclib + LY3214996 in Type 1 neurofibromatosis with NF1 Oncogenic mutations (germline): 4

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. References: 37406085

06 March, 2025 (Version: 20250306AU)

New ALTA-2618 in Breast cancer, Endometrial cancer with AKT1 E17K: 4

Preclinical study. The mutant-selective inhibitor of AKT1 E17K induced tumor regressions in multiple PDX models of breast and endometrial cancer models. References: 10.1158/1538-7445.AM2024-LB173

02 March, 2025 (Version: 20250302AU)

New AZD1390 + GSK126 in Mesothelioma with BAP1 Loss of protein expression, Oncogenic mutations: 4

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. References: 38519707

New Talazoparib in Myelodysplastic syndrome with SRSF2 P95H, Oncogenic mutations: 4

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. References: 38806724

New Cetuximab in Colorectal adenocarcinoma with ARID1A Oncogenic mutations: R2

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. References: 36117191

New Methotrexate in Acute lymphoblastic leukaemia with DHFR Amplification: R2

N=67, ALL patients, DHFR gene amplification (31%) correlated with p53 mutations (P < .001) is a mechanism of acquired resistance to methotrexate. References: 7605998

New Nivolumab + FLOX in Colorectal adenocarcinoma with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: R2

Randomized Phase 2. METIMMOX trial. NCT03388190. N=80. In microsatellite stable disease, no PFS advantage was observed with alternating FLOX + nivolumab over FLOX alone (both 9.2 months). References: 38664577

24 February, 2025 (Version: 20250224AU)

New Tuvusertib in Solid tumours with ARID1A Oncogenic mutation: 4

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. References: 38407317

New Tuvusertib in Solid tumours with ATRX Oncogenic mutation: 4

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. References: 38407317

New Tuvusertib in Solid tumours with BRCA1 Oncogenic mutation: 4

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. References: 38407317

New Tuvusertib in Solid tumours with BRCA2 Oncogenic mutation: 4

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. References: 38407317

New Tuvusertib in Solid tumours with DAXX Oncogenic mutation: 4

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. References: 38407317

New IMC-F106C in Melanoma with HLA-A2+PRAME HLA-A2:A*02:01 AND PRAME:Protein expression: 4

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). References: 10.1200/JCO.2024.42.16_suppl.9507

New Tuvusertib in Solid tumours with TP53 Oncogenic mutation: 4

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. References: 38407317

22 February, 2025 (Version: 20250222AU)

New Avutometinib + Defactinib in Non-small cell lung cancer with KRAS KRAS:Oncogenic mutations + CDH1:Protein expression + VIM:NOT Protein expresssion: 4

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. References: 38822146

New Larotrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, F589L, V573M, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib, Zurletrectinib in Solid tumours with NTRK1 LMNA-NTRK1 fusion, V573M, A608D: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib in Solid tumours with NTRK2 ETV6-NTRK2 fusion, V689M: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, F617L, G623E, G696A: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, G623E: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Zurletrectinib in Solid tumours with NTRK3 ETV6-NTRK3 fusion, G623E, G696A: 4

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib, Zurletrectinib in Solid tumours with NTRK1 F589L, G595R, G667A, G667C, G667S: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK1 F589L, G595R, G667A, G667C, G667S, V573M: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK1 G595R, G667A, G667C, G667S: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib, Selitrectinib, Zurletrectinib, Repotrectinib in Solid tumours with NTRK2 F633L, G639R, G709C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Larotrectinib in Solid tumours with NTRK3 F617L, G623R, G623E, G696A, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Selitrectinib in Solid tumours with NTRK3 F617L, G623R, G696A, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Zurletrectinib in Solid tumours with NTRK3 F617L, G623R, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

New Repotrectinib in Solid tumours with NTRK3 G623R, G623E, G696C: R2

Preclinical study. Zurletrectinib showed high potency against mutant Trk-kinases and brain penetration compared to first-generation in NTRK fusion-positive tumor models. References: 38902532

Changed Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600: 2

References changed: 37733309, 10.1200/JCO.2022.40.17_suppl.LBA200210.1056/NEJMoa2303815, 10.1200/JCO.2022.40.17_suppl.LBA2002. (First curated: 2021-06-20)

Changed Vorasidenib in Low-grade gliomas with IDH1 Oncogenic mutation: 2

References changed: 3727251610.1056/NEJMoa2304194. (First curated: 2023-06-05)

Changed Vorasidenib in Low-grade glioma with IDH2 Oncogenic mutation: 2

References changed: 3727251610.1056/NEJMoa2304194. (First curated: 2023-06-05)

21 February, 2025 (Version: 20250221AU)

New SP2509 in Non-small cell lung cancer with DNMT3A Oncogenic mutations, Deletions, Truncating mutations, Loss-of-function mutations: 4

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. References: 38951697

New Isotretinoin + Navitoclax in Neuroblastoma with MYC Amplification: 4

Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models. References: 38942989

New Isotretinoin + Navitoclax in Neuroblastoma with MYCN Amplification: 4

Preclinical study. Retinoic acid combined with navitoclax induces apoptosis in MYC(N)-driven embryonal nervous system tumors, including group 3 medulloblastoma and neuroblastoma models. References: 38942989

New Carboplatin + Etoposide, Cisplatin + Etoposide in Gastrointestinal neuroendocrine carcinoma with BRAF V600: R2

Retrospective analysis. N=229. BRAF alterations were not associated with response to platinum etoposide in gastrointestinal high-grade neuroendocrine neoplasms. References: 38909137

17 February, 2025 (Version: 20250217AU)

New Rucaparib + VE-821, Rucaparib + PF-477736, Rucaparib + MK-1775 in Ovarian cancer with BRCA1+BRCA2 NOT BRCA1:Oncogenic mutations and NOT BRCA2:Oncogenic mutations: 4

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. References: 38965423

16 February, 2025 (Version: 20250216AU)

New Odronextamab in Follicular lymphoma with CD20 Protein expression: 3

Phase II 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. References: 39147364

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 4

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. References: 39198618

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 4

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. References: 39198618

New Nivolumab in Hepatocellular carcinoma with CD274 Protein expression: 4

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. References: 38151184

New Oxaliplatin in Pancreatic adenocarcinoma with BRCA2 Reversion mutations: R2

Retrospective analysis of the Phase 2 GOZILA trial. N=702. Reversion mutation of BRCA2 gene was identified in two patients. References: 39198618

New Palbociclib, Ribociclib, Abemaciclib in Breast cancer with CDK4 Amplification: R2

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. References: 39090361

New Capivasertib in Gastric cancer with ARID1A Oncogenic mutation: 4

Preclinical study. AKT inhibition showed synthetic lethality in ARID1A-deficient gastric cancer cells via pyroptosis induction through Caspase-3/GSDME pathway activation. References: 39003371

New Trastuzumab in Extramammary Paget’s disease with 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: R2

Preclinical study. In PDX models, trastuzumab-resistant EMPD model showed PTEN loss as a resistance mechanism. References: 38987365

New Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA1 Oncogenic mutations: 4

Phase Ib. 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. References: 38971950

New Atezolizumab + Rucaparib in Ovarian cancer, Triple-negative breast cancer with BRCA2 Oncogenic mutations: 4

Phase Ib. 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. References: 38971950

14 February, 2025 (Version: 20250214AU)

Changed Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2

Comments changed: 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.. (First curated: 2023-11-17)

10 February, 2025 (Version: 20250210AU)

New MDNA11 in Solid tumours with Microsatellite Instability High: 4

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. References: 10.1158/1538-7445.AM2024-CT259

09 February, 2025 (Version: 20250209AU)

New VRN101099 in Breast cancer with ERBB2 Overexpression, Amplification: 4

Preclinical study. VRN101099, a brain-permeable HER2 kinase inhibitor, showed anti-tumor activity in HER2-positive cancer models with nanomolar potency. References: 10.1158/1538-7445.SABCS22-P1-11-03

07 February, 2025 (Version: 20250207AU)

Changed Fam-trastuzumab deruxtecan-nxki in Colorectal cancer with ERBB2 Overexpression: 2

Tier changed: 23. Comments changed: 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).. (First curated: 2024-08-29)

Changed Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion: 2

Comments changed: 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.Not TGA approved. FDA approved (accelerated). Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months.. References changed: 39908431, 10.1200/JCO.2022.40.16_suppl.105. (First curated: 2022-06-15)

06 February, 2025 (Version: 20250206AU)

New Pemigatinib in Urothelial carcinoma with FGFR3 Fusion, R248C, S249C, S764fs*6, G370C, S371C, Y373C: 3

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. References: 37956738

New Erdafitinib in Urothelial carcinoma with FGFR3 S249C, Y373C, R248C, G370C, R248C, FGFR3 fusions, FGFR3-TACC3 fusion, FGFR3-TACC3_V1 fusion, FGFR3-TACC3_V3 fusion, FGFR3-BAIAP2L1 fusion: 3

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). References: 37871702

New BBO-10203 in Breast cancer with ERBB2 Amplification, Overexpression: 4

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. References: 10.1158/1538-7445.SABCS23-RF02-02

New Capmatinib in Non-small cell lung cancer with MET CD74-MET fusion: 4

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. References: 38832711

New Olaparib in Breast cancer with BRCA1 Reversion mutations: R2

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. References: 38244928

New Olaparib in Breast cancer with BRCA2 Reversion mutations: R2

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. References: 38244928

New Pemigatinib in Urothelial carcinoma with FGFR3 V553M, V555L, V555M, M528I, N540S, N540K: R2

Phase 2. FIGHT-201. NCT02872714. N=260. Secondary acquired on-target resistance mutations detected at end of treatment in 6 patients. References: 37956738

New Olaparib in Breast cancer with PAXIP1 Oncogenic mutations: R2

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. References: 38244928

New Olaparib in Breast cancer with RIF1 Oncogenic mutations: R2

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. References: 38244928

New Olaparib in Breast cancer with TP53BP1 Oncogenic mutations: R2

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. References: 38244928

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1

Tier changed: 1B. Comments changed: 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%.TGA approved. Not 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%.. (First curated: 2022-01-28)

Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1

Tier changed: 1B. Comments changed: 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%).TGA approved. Not 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%).. (First curated: 2023-10-29)

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Amplification; Overexpression: 1B

Comments changed: 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.TGA approved. FDA approved. DESTINY-Breast01: In patients with prior anti-HER2 therapies, median DOR 14.8mo, PFS 16.4mo. HER2 positivity: defined as IHC 3+ or FISH positive.. References changed: 31825192, 38092229. (First curated: 2020-05-12)

04 February, 2025 (Version: 20250204AU)

New GSK_WRN4 in Solid tumours with Microsatellite Instability High: 4

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. References: 38587317

03 February, 2025 (Version: 20250203AU)

New Patritumab deruxtecan in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, L861Q, G719: 3

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. References: 38369013

New Patritumab deruxtecan in Non-small cell lung cancer with ERBB3 Truncating mutations, Y789fs: R2

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. References: 38369013

New Patritumab deruxtecan in Non-small cell lung cancer with TOP1 L721R: R2

References: 38369013

20 January, 2025 (Version: 20250120AU)

New Avelumab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 4

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. References: 38704093

New Avelumab + Carboplatin + Paclitaxel in Endometrial cancer with ARID1A Oncogenic mutations: 4

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. References: 38704093

19 January, 2025 (Version: 20250119AU)

New Camizestrant in Breast cancer with ESR1 E380Q, S463P, V422del, L536P, L536H, Y537C, Y537D, Y537N, Y537S, D538G: 3

Phase I. 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). References: 38729567

New Camizestrant in Breast cancer with ESR1+ERBB2 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3

Phase I. 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). References: 38729567

New Durvalumab, Ipilimumab + Nivolumab, Nivolumab, Pembrolizumab in Colorectal cancer with POLD1 D402N, L606M: 3

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. References: 38777726

New Durvalumab, Ipilimumab + Nivolumab, Nivolumab, Pembrolizumab in Colorectal cancer with POLE P286R, S297Y, S297F, F367S, V411L, L424I, P436R, S459F, A456P: 3

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. References: 38777726

Changed Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 1

Comments changed: 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.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.. References changed: 36972026, 38866180. (First curated: 2023-12-16)

13 January, 2025 (Version: 20250113AU)

New Neratinib + Trastuzumab emtansine in Breast cancer with ERBB2 Overexpression, Amplification: 3

Phase 2. TBCRC022 Cohort 4. N=44. Neratinib + ado-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. References: 38977064

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA1 Oncogenic mutations: 1

Comments changed: 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%.TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012.. References changed: 31562799, 39284381. (First curated: 2020-04-25)

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with BRCA2 Oncogenic mutations: 1

Comments changed: 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%.TGA approved. Not PBS reimbursed. PRIMA/ENGOT-OV26/GOG-3012.. References changed: 31562799, 39284381. (First curated: 2020-04-25)

Changed Niraparib in Ovarian cancer, Peritoneal serous carcinoma, Fallopian tube carcinoma with Homologous Recombination Deficiency Score High: 1

Tier changed: 12. Comments changed: 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%.Biomarker not approved by TGA. Not 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.. References changed: 31562799, 39284381. (First curated: 2020-05-04)

12 January, 2025 (Version: 20250112AU)

New Mirvetuximab soravtansine in Ovarian cancer with FOLR1 Protein expression, Overexpression: 3

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. References: 39617145

New Ipilimumab + Nivolumab in Prostate cancer with Microsatellite Instability High: 3

Phase II 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. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Mismatch repair Deficient: 3

Phase II 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. References: 39293514

New BMS-986365 in Prostate cancer with AR L702H, L702H and H875Y, L702H and T878A, L702H and W742C and T878A, T878A, W742C and T878A: 4

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. References: 39293515

New Ipilimumab + Nivolumab in Prostate cancer with BRCA2 Oncogenic mutation: R2

Phase II 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. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with CDK12 Oncogenic mutation: R2

Phase II 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. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Microsatellite Instability Tumour Mutational Burden:High and NOT Microsatellite instability:high: R2

Phase II 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. References: 39293514

New Ipilimumab + Nivolumab in Prostate cancer with Tumour Mutational Burden+Mismatch repair Tumour Mutational Burden:High and NOT Mismatch repair:deficient: R2

Phase II 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. References: 39293514

Changed Pembrolizumab + Cisplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Carboplatin + Paclitaxel + Bevacizumab, Pembrolizumab + Cisplatin + Paclitaxel, Pembrolizumab + Carboplatin + Paclitaxel in Cervical cancer with CD274 Protein expression: 1

Tier changed: 12. Comments changed: 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.Not 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.. References changed: 34534429, 39393777. (First curated: 2021-09-19)

Changed Pembrolizumab in Colorectal adenocarcinoma with Mismatch repair Deficient: 1

Comments changed: 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.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. MMR deficient is defined by absence of expression of one of MLH1, MSH2, MSH6, or PMS2 as assessed by IHC.. References changed: 33264544, 39631622, 10.1200/JCO.2020.38.18_suppl.LBA433264544, 10.1200/JCO.2020.38.18_suppl.LBA4. (First curated: 2020-12-11)

09 January, 2025 (Version: 20250109AU)

New Futibatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, E7090 in Cholangiocarcinoma with FGFR2 K642I: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Pemigatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 K660N: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550H, N550K, E566A, E566G, L618M, L618V: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550K, N550D, K660M: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Pemigatinib, Erdafitinib, E7090 in Cholangiocarcinoma with FGFR2 V563L, E566A, E566G, K642R: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 V565I: 4

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Futibatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565F: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib in Cholangiocarcinoma with FGFR2 BCR-FGFR2 fusion AND V565I, BCR-FGFR2 fusion AND N550K: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Infigratinib, Erdafitinib, Zoligratinib in Cholangiocarcinoma with FGFR2 K642I: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Infigratinib in Cholangiocarcinoma with FGFR2 K660N: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Infigratinib, Erdafitinib in Cholangiocarcinoma with FGFR2 N550H, N550K, E566A, E566G, L618M, L618V: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib,Infigratinib, Erdafitinib, E7090, Zoligratinib in Cholangiocarcinoma with FGFR2 N550K, N550D, K660M: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Infigratinib, Zoligratinib in Cholangiocarcinoma with FGFR2 V563L, E566A, E566G, K642R: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Derazantinib, Zoligratinib, AZD4547, Futibatinib in Cholangiocarcinoma with FGFR2 V565I: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Pemigatinib, Derazantinib, Zoligratinib, AZD4547, Futibatinib, Erdafitinib in Cholangiocarcinoma with FGFR2 V565L: R2

Multimodal analysis of acquired resistance to FGFR inhibitors in cholangiocarcinoma: 138 patients, 486 clinical samples, 26 distinct FGFR2 kinase domain mutations identified. References: 39706336

New Futibatinib in Cholangiocarcinoma with FGFR2 N550, L552F, V565, E566A, L618V, N653S: R2

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. References: 39672383

New Disitamab vedotin + Toripalimab in Urothelial carcinoma with ERBB2 Overexpression, Protein expression, Low protein expression: 3

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. References: 39662628

Changed Therapy in Solid tumours with FGFR1 Fusion: 4

Therapy changed: ZoligratinibDebio1347. (First curated: 2020-06-11)

Changed Therapy in Cholangiocarcinoma with FGFR2 Extracellular domain deletion, H167_N173del, L618F: 4

Therapy changed: ZoligratinibDebio1347. Comments changed: Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Zoligratinib experienced treatment response.Case reports. Two of 3 cholangiocarcinoma patients with FGFR2 extracellular domain in-frame deletions treated with Debio1347 experienced treatment response.. (First curated: 2022-09-28)

Changed Therapy in Solid tumours with 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: 4

Therapy changed: AZD4547, Pemigatinib, ZoligratinibAZD4547, Pemigatinib, Debio1347. (First curated: 2024-11-22)

Changed Therapy in Solid tumours with FGFR1 V561M: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347. (First curated: 2020-05-22)

Changed Therapy in Cholangiocarcinoma with FGFR2 L618F: R2

Therapy changed: ZoligratinibDebio1347. (First curated: 2022-09-28)

Changed Therapy in Solid tumours with FGFR2 V565I, N550K, V564M, V564F: R2

Therapy changed: Infigratinib, AZD4547, Zoligratinib, Dovitinib, PonatinibInfigratinib, AZD4547, Debio1347, Dovitinib, Ponatinib. (First curated: 2020-05-22)

Changed Therapy in Cholangiocarcinoma with FGFR3 N540K, V555M, L608V: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347. (First curated: 2023-02-22)

Changed Therapy in Solid tumours with FGFR3 V443, V555M: R2

Therapy changed: Infigratinib, AZD4547, ZoligratinibInfigratinib, AZD4547, Debio1347. (First curated: 2020-05-22)

06 December, 2024 (Version: 20241206AU)

New Revumenib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Mixed phenotype acute leukaemia with KMT2A Rearrangement: 2

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. References: 39121437

New Revumenib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with KMT2A Rearrangement: 3

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. References: 36922593

New Zenocutuzumab in Solid tumours with NRG1 Fusion, CD74-NRG1 fusion, CLU-NRG1 fusion, ATP1B1-NRG1 fusion, SLC3A2-NRG1 fusion, APP-NRG1 fusion: 4

N=3. 2/3 patients with NRG1 fusion-positive metastatic cancer achieved rapid responses, including 2 with ATP1B1-NRG1 pancreatic cancer and 1 with CD74-NRG1 non-small cell lung cancer. References: 35135829

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 2

Comments changed: 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.Not TGA approved. FDA approved. Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months.. (First curated: 2023-06-04)

Changed Zenocutuzumab in Solid tumours with NRG1 CD74-NRG1 fusion, SLC3A2-NRG1 fusion, ATP1B1-NRG1 fusion, SDC4-NRG1 fusion, RBPMS-NRG1 fusion, CDH1-NRG1 fusion, VTCN1-NRG1 fusion: 2

Tier changed: 23. Comments changed: Not TGA approved. FDA approved (accelerated). Updated results from phase 1/2 eNRGy trial. N=110. ORR 34% (27/84), including 42% in PDAC and 35% in NSCLC. Median DOR 9.1 months.. (First curated: 2022-06-15)

04 December, 2024 (Version: 20241204AU)

Changed Belzutifan in Hemangioblastoma with VHL Oncogenic mutations (germline): 1

Tier changed: 1B. Comments changed: 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.TGA approved. Not PBS reimbursed. 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.. (First curated: 2023-07-24)

Changed Belzutifan in Pancreatic neuroendocrine tumour, Hemangioblastoma with VHL Oncogenic mutations (germline): 1

Tier changed: 1B. Comments changed: TGA approved. PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas.TGA approved. Not PBS listed. FDA approved. MK-6482-004. N=61. ORR 77% (47/61) for pancreatic lesions,and 320 (16/50) CNS hemangioblastomas.. (First curated: 2021-12-02)

Changed Belzutifan in Renal cell carcinoma with VHL Oncogenic mutations (germline): 1

Tier changed: 1B. Comments changed: 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%.TGA approved. Not 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%.. (First curated: 2021-09-15)

02 December, 2024 (Version: 20241202AU)

New Trastuzumab in Breast cancer with ERBB2 p95 expression: R2

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. References: 17440164

New Lapatinib in Breast cancer with ERBB2 p95 expression: 4

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. References: 17440164

22 November, 2024 (Version: 20241122AU)

New BWA-522 in Prostate cancer with AR AR-FL; AR-V7: 4

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. References: 37556600

New CC-94676 in Prostate cancer with AR Wildtype, Amplifications, Oncogenic mutations: 4

Phase 1. NCT04428788. in metastatic castration-resistant prostate cancer patients, CC-94676 34% of patients achieved PSA30 across all dose levels. References: 10.1200/JCO.2024.42.4_suppl.134

New AZD4547, Pemigatinib, Debio1347 in Solid tumours with 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: 4

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. References: 35948633

Changed Zanidatamab in Biliary tract cancer with ERBB2 Protein expression; Overexpression: 2

Tier changed: 23. Comments changed: Not TGA approved. FDA approved. Phase 2. HERIZON-BTC-01. NCT04466891. In Cohort 1 IHC 2+/3+, ORR 33/80 (41%). Median PFS 5.5 months.. (First curated: 2023-06-04)

Changed Bemarituzumab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma, Oesophageal adenocarcinoma with FGFR2 : 4

Alterations changed: Overexpression, FGFR2b:Overexpression, FGFR2-IIIb:Overexpression. (First curated: 2022-11-01)

Changed Bemarituzumab in Gastroesophageal junction adenocarcinoma, Gastric Cancer with FGFR2 : 4

Alterations changed: Overexpression, FGFR2b:Overexpression, FGFR2-IIIb:Overexpression, amplification. (First curated: 2020-06-26)

13 November, 2024 (Version: 20241113AU)

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with BRCA1 Oncogenic mutations: 4

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). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with BRCA2 Oncogenic mutations: 4

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). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with PALB2 Oncogenic mutations: 4

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). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with RAD51C Oncogenic mutations: 4

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). References: 10.1200/JCO.2024.42.16_suppl.3154

New HRS-1167 in Ovarian cancer, Prostate cancer, Pancreatic cancer with RAD51D Oncogenic mutations: 4

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). References: 10.1200/JCO.2024.42.16_suppl.3154

05 November, 2024 (Version: 20241105AU)

New Zolbetuximab + FOLFOX in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: 3

Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma. References: 37490286

New Zolbetuximab, Zolbetuximab + Pembrolizumab in Gastric cancer, Gastroesophageal junction adenocarcinoma with CLDN18 Protein expression: R2

Phase 2 ILUSTRO trial. N=54. Zolbetuximab did not show objective response rate (ORR) as monotherapy or in combination with pembrolizumab, but showed promising efficacy when combined with mFOLFOX6 (ORR: 71.4%, median PFS: 17.8 months) in CLDN18.2-positive gastric/gastroesophageal junction adenocarcinoma. References: 37490286

04 November, 2024 (Version: 20241104AU)

New Gefitinib in Non-small cell lung cancer with CRKL Amplification: R2

Preclinical study. CRKL amplification induces transformation and EGFR inhibitor resistance, activates SOS1-RAS-RAF-ERK and SRC-C3G-RAP1 pathways in NSCLC lines. References: 22586683

New Atezolizumab in Hepatocellular carcinoma with CRKL Amplification, Overexpression: R2

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. References: 38403027