History of database changes

25 March, 2024 (Version: 20240325AU) (Latest version)

Changed Pembrolizumab in Head and neck squamous cell carcinoma with CD274 Protein expression: 1
Tier changed: 1B. Comments changed: TGA approved. Not PBS reimbursed. Approved for CPS >= 1; PBS-subsidised if the PD-L1 CPS >= 20 in the tumour sample.. (First curated: 2020-04-16)
Changed Pembrolizumab + Nab-paclitaxel, Pembrolizumab + Paclitaxel, Pembrolizumab + Carboplatin + Gemcitabine in Triple-negative breast cancer with CD274 Protein expression: 1
Tier changed: 12. Comments changed: TGA approved. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo. Median OS was significantly longer in pembrolizumab plus chemotherapy group (23.0 months) versus chemotherapy alone (16.1 months).Not TGA approved. FDA accelerated approval. KEYNOTE-355: First-line pembrolizumab combination with chemotherapy in TNBC with PD-L1 expression (defined as combined positive score of >= 10%). PFS 9.7 v 5.6mo. Median OS was significantly longer in pembrolizumab plus chemotherapy group (23.0 months) versus chemotherapy alone (16.1 months).. (First curated: 2020-05-30)
Changed Pembrolizumab in Cervical cancer with CD274 Protein expression: 1B
Tier changed: 1B2. Comments changed: Not TGA approved. KEYNOTE-028: Phase 1b. ORR 17%. KEYNOTE-158: ORR 15%. PD-L1 positivity defined as CPS >= 1% (22C3 pharmDx assay).. (First curated: 2020-04-16)
Changed Pembrolizumab + Cisplatin + Fluorouracil in Oesophageal cancer, Oesophageal Adenocarcinoma, Oesophageal squamous cell carcinoma with CD274 Protein expression: 1B
Tier changed: 1B2. Comments changed: TGA approved. Phase 3 KEYNOTE-590. FDA approved 2021-03-22. In the first-line setting, adding pembrolizumab to chemotherapy resulted in superior OS in PD-L1 positive subgroups (defined as CPS ≥ 10%, median 13.5 versus 9.4 mo), but also in ESCC and overall populations. Overall ORR in pembrolizumab arm was 45% (vs control 23%).. (First curated: 2020-09-29)
Changed Pembrolizumab in Cervical cancer, Endometrial cancer, Neuroendocrine tumour, Salivary gland cancers, Small-cell lung cancer, Thyroid cancer, Vulvar cancer with Tumour Mutational Burden High: 1B
Tier changed: 1B2. Comments changed: TGA provisionally approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H). TMB cut-off at 10mut/MB.Not TGA approved. KEYNOTE-158. The following cancer types have higher ORR in TMB-H cohort (vs non-TMB-H). TMB cut-off at 10mut/MB.. (First curated: 2020-09-25)
Changed Nivolumab + Ipilimumab in Non-small cell lung cancer with Tumour Mutational Burden High: 1B
Tier changed: 1B2. Comments changed: TGA provisionally approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB.Not TGA approved. Phase 3 CHECKMATE 227. Prespecified, prospective TMB cutoff of 10mut/MB in 57% of cohort. Median PFS: 7.2 vs 5.5 months. Not correlated with TMB.. (First curated: 2020-11-26)

21 March, 2024 (Version: 20240321AU)

Changed Therapy in Solid tumours with CD274 Amplification: 4
Therapy changed: Anti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1-targetingAnti-PD-1 monoclonal antibody, immune checkpoint blockade,PD-L1 targeting. (First curated: 2020-04-16)

19 March, 2024 (Version: 20240319AU)

New Pembrolizumab + Fluorouracil + Cisplatin, Pembrolizumab + Capecitabine + Oxaliplatin in Gastric cancer, Gastroesophageal junction adenocarcinoma with ERBB2+CD274 CD274:Protein expression and NOT ERBB2:Amplification and NOT ERBB2:Overexpression: 1B
Not PBS listed. TGA approved without biomarker. Phase 3. KEYNOTE-859. NCT03675737. N=1579. Pembrolizumab + chemotherapy significantly improved OS over chemotherapy alone in HER2-negative gastric or gastro-esophageal junction adenocarcinoma. In subgroup analysis, OS (versus placebo) was longer in PD-L1 CPS >= 1 and >= 10 subgroups but not in the <1 subgroup. References: 37875143

18 March, 2024 (Version: 20240318AU)

Changed Fam-trastuzumab deruxtecan-nxki in Breast cancer with ERBB2 Protein expression and NOT Amplification, Low protein expression and NOT Amplification: 1B
Comments changed: Not TGA approved. Phase 3. DESTINY-Breast04. NCT03734029. Compared with physician’s choice, T-DXD prolonged both PFS (10.1 v 5.4 months) and OS (23.9 v 17.5 months) in Hormone receptor-positive, HER2-low metastatic breast cancer. Similarly T-DXD also prolonged PFS (9.9 v 5.1 months) and OS (23.4 vs 16.8 months) compared to physician’s choice in the overall population. HER2-Low was defined as IHC a score of 1+ or 2+ with negative results on in situ hybridization. FDA approved 5/8/2022.. (First curated: 2021-06-05)

26 February, 2024 (Version: 20240226AU)

New Sotorasib, JQD443, RM-018 in Solid tumour with HRAS G12C: 4
Preclinical study. Sotorasib is a potent NRASG12C inhibitor, more potent than KRASG12C (5-fold) in vitro. In addition, sotorasib is also a HRASG12C inhibitor. This was demonstrated by the clinical response of a patient with NRASG12C colorectal cancer treated with sotorasib and panitumumab. References: 38236605
New Sotorasib, JQD443, RM-018 in Solid tumour with NRAS G12C: 4
Preclinical study. Sotorasib is a potent NRASG12C inhibitor, more potent than KRASG12C (5-fold) in vitro. In addition, sotorasib is also a HRASG12C inhibitor. This was demonstrated by the clinical response of a patient with NRASG12C colorectal cancer treated with sotorasib and panitumumab. References: 38236605
New Adagrasib, GDC6036 in Solid tumour with HRAS G12C: R2
Preclinical study. Both adagrasib and GDC6036 are KRAS G12C specific inhibitors. References: 38236605
New Cisplatin + Etoposide, Carboplatin + Etoposide, Olaparib + Temozolomide, Topotecan in Small-cell lung cancer with MYC Amplification: R2
Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients. References: 38386926
New Cisplatin + Etoposide, Carboplatin + Etoposide, Olaparib + Temozolomide, Topotecan in Small-cell lung cancer with MYCL Amplification: R2
Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients. References: 38386926
New Cisplatin + Etoposide, Carboplatin + Etoposide, Olaparib + Temozolomide, Topotecan in Small-cell lung cancer with MYCN Amplification: R2
Preclinical study. Serial PDX models revealed that cross-resistance was acquired through MYC amplification on extranuclear DNA (ecDNA). Genomic and transcriptional profiles of the full PDX panel revealed that MYC paralog amplifications on ecDNAs were recurrent in relapsed cross-resistant SCLC with corroboration from tumour biopsies from relapsed patients. References: 38386926
New Adagrasib, GDC6036 in Solid tumour with NRAS G12C: R2
Preclinical study. Both adagrasib and GDC6036 are KRAS G12C specific inhibitors. References: 38236605

09 February, 2024 (Version: 20240209AU)

Changed Enasidenib in Acute myeloid leukaemia with IDH2 : 1B
Alterations changed: R140Q, R140, R172K, R172SR140Q, R172K, R172S. (First curated: 2020-05-07)

31 January, 2024 (Version: 20240131AU)

New PF-07104091 in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3
Phase 1, NCT04553133. In 16 RECIST evaluable HR+/HER2- metastatic breast cancer, ORR was 19% (n=3). DCR was 62%. References: 10.1200/JCO.2023.41.16_suppl.3010
New PF-07220060 in Breast cancer with ERBB2+ESR1 ESR1:Protein expression and NOT ERBB2:amplification and NOT ERBB2:overexpression: 3
Phase 1/2a study. PF-07220060 alone or with endocrine therapy in HR+/HER2- metastatic breast cancer with prior endocrine therapy and CDK4/6 inhibitors exposure. ORR was 29%. Median PFS of 25 weeks. References: 10.1200/JCO.2023.41.16_suppl.3009

22 January, 2024 (Version: 20240122AU)

New Olaparib, Talazoparib in Acute myeloid leukaemia with IDH1 Oncogenic mutation: 4
In vitro study. Increased DNA damage and sensitization to daunorubicin, ionizing radiation, and PARP inhibitors were observed in IDH1/2MUT AML cells. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells. References: 29339439
New Olaparib, Talazoparib in Acute myeloid leukaemia with IDH2 Oncogenic mutation: 4
In vitro study. Increased DNA damage and sensitization to daunorubicin, ionizing radiation, and PARP inhibitors were observed in IDH1/2MUT AML cells. Combined treatment with a PARP inhibitor and daunorubicin had an additive effect on the killing of IDH1/2MUT AML cells. References: 29339439

12 January, 2024 (Version: 20240112AU)

Changed Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2
References changed: 38197815, 10.1200/JCO.2023.41.16_suppl.9017. (First curated: 2023-11-17)

07 January, 2024 (Version: 20240107AU)

New Ripretinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation: R2
Exploratory ctDNA analysis from Phase 3 INTRIGUE trial. Ripretinib showed significantly inferior PFS to Sunitinib (Median PFS 4.0 v 15.0 months) in patients with KIT exon 13/14 co-mutation. References: 38182785, 10.1200/JCO.2023.41.36_suppl.397784
Changed Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 13 mutation, Exon 11 mutation and Exon 14 mutation: 3
References changed: 38182785, 10.1200/JCO.2023.41.36_suppl.397784. (First curated: 2023-01-25)
Changed Therapy in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation: 3
Therapy changed: RipretinibSunitinib. References changed: 38182785, 10.1200/JCO.2023.41.36_suppl.397784. (First curated: 2023-01-25)
Changed Sunitinib in Gastrointestinal stromal tumour with KIT Exon 11 mutation and Exon 17 mutation, Exon 11 mutation and Exon 18 mutation: R2
References changed: 38182785, 10.1200/JCO.2023.41.36_suppl.397784. (First curated: 2023-01-25)

29 December, 2023 (Version: 20231229AU)

New Tamoxifen in Breast cancer with FGFR1 Amplification: R2
Amplification was determined by CISH, if >50% of cells harbored either >5 copies. References: 20179196
Changed Ripretinib in Gastrointestinal stromal tumour with KIT Protein expression; Oncogenic mutations: 1
Tier changed: 1B. Comments changed: TGA approved. PBS Reimbursed for patients with GIST who received prior treatment with 3 or more kinase inhibitors;TGA approved for patients with GIST who received prior treatment with 3 or more kinase inhibitors; Not PBS Reimbursed.. (First curated: 2020-05-20)

27 December, 2023 (Version: 20231227AU)

New Trastuzumab + Pertuzumab + Paclitaxel in Extramammary Paget’s disease with ERBB2 Overexpression: 4
Case report. Single complete responder to pertuzumab, trastuzumab, and weekly paclitaxel. References: 37595182
New EPI-7386 in Prostate cancer with AR AR-V7: 4
References: 10.1093/annonc/mdz244.065

22 December, 2023 (Version: 20231222AU)

New Vemurafenib in Hairy cell leukaemia, Erdheim-Chester disease with BRAF V600: 3
Phase 2. AcSé vemurafenib basket study. NCT01895643. N=98. Vemurafenib showed clinical activity in BRAF mutated cancers including HCL (ORR 89.7%), ECD (80%), ovarian cancer (50%) and cholangiocarcinoma (18%). Median PFS was 8.8 months. Response were also seen in glioblastoma, ovarian, xanthoastrocytoma, ganglioglioma, sarcoma, GI adenocarcinoma, and prostate cancer. References: 37922690
New Vemurafenib in Solid tumour with BRAF V600: 3
Phase 2. AcSé vemurafenib basket study. NCT01895643. N=98. Vemurafenib showed clinical activity in BRAF mutated cancers including HCL (ORR 89.7%), ECD (80%), ovarian cancer (50%) and cholangiocarcinoma (18%). Median PFS was 8.8 months. Response were also seen in glioblastoma, ovarian, xanthoastrocytoma, ganglioglioma, sarcoma, GI adenocarcinoma, and prostate cancer. References: 37922690
New Dabrafenib + Trametinib in Melanoma with BRAF T599_V600insT: 4
Case series. References: 35319964
New Vemurafenib in Melanoma with BRAF T599_V600insT: 4
Phase 2. AcSé vemurafenib basket study. NCT01895643. One responder seen in melanoma harbouring T599dup. References: 37922690
New Vemurafenib in Melanoma with BRAF T599_V600insT: R2
Case series. No response was seen in two patients with BRAF T599dup. References: 35319964

20 December, 2023 (Version: 20231220AU)

New Atezolizumab + Cobimetinib in Colorectal cancer with KRAS Oncogenic mutations: R2
Phase 3 IMblaze 370 trial. NCT02788279. N=363. Atezolizumab plus cobimetinib did not improve OS compared to regorafenib in patients with MSS colorectal cancer and disease progression on or intolerance to at least two previous chemotherapy regimens. ORR in RAS mutant group was 1/99 (1%). References: 31003911
New Cetuximab, Panitumumab in Colorectal cancer with EGFR G63R, E114K, R165Q, R222C, S492R, P596L, K708R, E709K, G719S, G724S, L858R: 4
Preclinical study. Somatic EGFR mutations in colon cancer were identified by systematic functional screening and demonstrated to be oncogenic, ligand-independent and transform cells in vitro and responsive to cetuximab or panitumumab both in vitro and in vivo. References: 31290142

17 December, 2023 (Version: 20231217AU)

New Garsorasib in Colorectal adenocarcinoma with KRAS G12C: 3
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%. References: 10.1200/JCO.2023.41.16_suppl.3563

16 December, 2023 (Version: 20231216AU)

New Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Microsatellite Instability High: 2
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: 36972026
New Dostarlimab + Carboplatin + Paclitaxel in Endometrial cancer with Mismatch repair Deficient: 2
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: 36972026
Changed Enfortumab Vedotin in Urothelial carcinoma with NECTIN4 Protein expression: 1
Tier changed: 12. Comments changed: TGA approved. PBS reimbursed. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells.Not TGA approved. FDA approved. ORR 44%. Nectin-4 expression was not required for entry into the trial, given that it is highly expressed on urothelial carcinoma cells.. (First curated: 2021-02-15)

14 December, 2023 (Version: 20231214AU)

New Trametinib in Non-small cell lung cancer with GNAS R201C, R201H: 4
Case report. References: 35946511
New Trametinib in Appendiceal cancer with GNAS R201H: 4
Case report. References: 28868010
New MRTX1719 in Solid tumour, Mesothelioma, Non-small cell lung cancer, Gallbladder cancer, Malignant peripheral nerve sheath tumor with MTAP Deletion: 4
Phase 1 trial and preclinical study. NCT05245500. In vitro cell line models and xenografts studies. MRTX1719 selectively inhibited PRMT5 in MTAP-deleted tumor cells with minimal effects on normal hematopoietic cells. Early clinical activity were observed in patients seleced cancer types. References: 37552839
New Osimertinib in Non-small cell lung cancer with GNAS R201C, R201H: R2
Case report. References: 35946511

09 December, 2023 (Version: 20231209AU)

New Mirvetuximab soravtansine in Ovarian cancer with FOLR1 Protein expression: 2
Phase 3 trial. MIRASOL. NCT04209855. N=453. In platinum-resistant ovarian cancer, Mirvetuximab soravtansine showed significant improvement in PFS (median, 5.6 months v chemotherapy, 3.9 months), ORR (42% vs 16%) and OS (16.5 vs 12.8 months) over chemotherapy. References: 38055253
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with ALK EML4-ALK fusion: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with BRAF Amplification, V600E: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with EGFR Amplification: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with ERBB2 Amplification: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with HRAS G13V: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with KRAS Amplification, A11_G12delinsGD, G12R, G12S, G13D, H95N, Q61H, Q61L, R68S, Y96D: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with MAP2K1 E203K, K57N, Q56P: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with MET Amplification: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with MYC Amplification: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with NF1 Deletion: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with NRAS Amplification, G13R, Q61R: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PIK3CA E545K: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PIK3R2 G373R: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with PTEN Oncogenic mutation, Deletion: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with RET CCDC6-RET fusion: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
New Divarasib, Divarasib + Cetuximab in Colorectal adenocarcinoma with ROS1 GOPC-ROS1 fusion: R2
Phase 1b trial. NCT04449874. GO42144. Potential treatment-emergent resistance mechanisms in ctDNA following divarasib plus cetuximab treatment in KRAS G12C-positive CRC. References: 38052910
Changed Divarasib + Cetuximab in Colorectal cancer with KRAS G12C: 2
Comments changed: Phase 1b trial. NCT04449874. GO42144. N=29. Divarasib plus cetuximab had a manageable safety profile and encouraging antitumor activity in KRAS G12C-positive CRC. The confirmed ORR was 63% (18/29, KRAS G12C inhibitor-naive patients). The median duration of response was 6.9 months, and the median PFS was 8.1 months.Phase 1b. NCT04449874. Confirmed ORR of 62% (18/29). Ongoing study.. References changed: 3805291010.1158/1538-7445.AM2023-CT029. (First curated: 2023-05-05)
Changed Buparlisib in Urothelial carcinoma with TSC1 Oncogenic mutations: R2
Comments changed: Phase 2. N=19. Buparlisib had modest activity in patients with metastatic UC whose tumors harbored TSC1 loss of function alterations (6 SD and one PR at 8 weeks on therapy).. (First curated: 2020-11-15)

08 December, 2023 (Version: 20231208AU)

New MTYX-5000 in Solid tumour, Non-small cell lung cancer with MET Overexpression: 4
Preclinical study. MYTX-011 showed activities in higher internalization in cMet+ tumor cells, cytotoxicity across a cMet+ cancer cell lines in vitro, and in NSCLC xenograft models. References: 10.1158/1538-7445.AM2023-5000

06 December, 2023 (Version: 20231206AU)

New GQ1001 in Solid tumour with ERBB2 Overexpression, amplification: 4
References: 10.1158/1538-7445.AM2023-2702
New INX-315 in Breast cancer with ESR1 Protein expression: 4
Preclinical study. INX-315 induces senescence in CCNE1-amplified luminal breast cancer cell lines, leading to growth control and overcoming and delaying breast cancer resistance to CDK4/6i. References: 38047585
New INX-315 in Breast cancer with ESR1+CCNE1 ESR1:Protein expression and CCNE1:Amplification: 4
Preclinical study. INX-315 induces senescence in CCNE1-amplified luminal breast cancer cell lines, leading to growth control and overcoming and delaying breast cancer resistance to CDK4/6i. References: 38047585
Changed BI-1810631 in Solid tumours with ERBB2 : 4
Alterations changed: Oncogenic mutations, Amplification. (First curated: 2023-07-18)
Changed Divarasib + Cetuximab in Colorectal cancer with KRAS G12C: 2
Tier changed: 24. (First curated: 2023-05-05)
Changed Therapy in Prostate cancer with AR AR-V7: R2
Therapy changed: Abiraterone acetate, Enzalutamide, Androgen receptor antagonist, CYP17A1 inhibitor. Comments changed: Phase 2. Detection of AR-V7 circulating tumour cells in metastatic castration resistant prostate cancer patients treated with enzalutamide or abiraterone showed a significant lower PFS, OS, and response rate compared to those without AR-V7.. (First curated: 2020-04-16)

05 December, 2023 (Version: 20231205AU)

New Garsorasib in Non-small cell lung cancer with KRAS G12C: 3
Phase 1. NCT04879671. N=79 (combined dose escalation and expansion). In patients with KRAS G12C mutated NSCLC, Treatment with D-1553 (Garsorasib) resulted in ORR of 40% and DCR of 92%. Median PFS was 8 months. References: 36948246
New Ipilimumab + Nivolumab in Solid tumour with ATM Oncogenic mutation: R2
Phase 2. TAPUR study. NCT02693560. N=29. ORR and PFS for nivolumab + ipilimumab in patients with ATM mutation (ORR 14%, DC rate 24%) did not meet the prespecified endpoints. References: 38039429

29 November, 2023 (Version: 20231129AU)

New Capivasertib + Fulvestrant in Breast cancer with AKT1 Oncogenic mutation: 2
Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy. References: 37256976
New Capivasertib + Fulvestrant in Breast cancer with PIK3CA Oncogenic mutation: 2
Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy. References: 37256976
New Capivasertib + Fulvestrant in Breast cancer with PTEN Loss-of-function mutations, deletion: 2
Not TGA approaved. FDA approved. Phase 3. CAPItello-291 trial. NCT04305496. N=708. Capivasertib plus fulvestrant significantly improved PFS over placebo plus fulvestrant 7.2 vs 3.6 months in the overall population, and 7.3 v 3.1 months in patients with AKT pathway alterations). ORR was 40% (placebo 35%). 69% had received previous CDK4/6 inhibitor therapy. References: 37256976
Changed Olaparib in Prostate cancer with BRCA1 Oncogenic mutations: 1
Comments changed: TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). Olaparib was associated with longer rPFS over control (HR, 0.22) and OS (HR, 0.63). rPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16).TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). (First curated: 2020-05-05)
Changed Olaparib in Prostate cancer with BRCA2 Oncogenic mutations: 1
Comments changed: TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. Phase 3 PROfound trial. NCT02987543. (cohort A, N=160): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control). Olaparib was associated with longer rPFS over control (HR, 0.22) and OS (HR, 0.63). rPFS benefit found in all zygosity subgroups. Risk of disease progression was similar for patients with germline (n = 61; HR, 0.08) and somatic (n = 51; HR, 0.16).TGA Approved. PBS listed for class 4 or 5 BRCA1 or BRCA2 gene mutation. PROFOUND trial (cohort A): Image-based PFS 7.4 mo (olaparib) v 3.6mo (control).. (First curated: 2020-05-05)
Changed Nirogacestat in Aggressive fibromatosis with APC Oncogenic mutations: 2
Comments changed: Not TGA approved. FDA approved 27/11/2023. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.Not TGA approved. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.. (First curated: 2023-03-25)
Changed Nirogacestat in Aggressive fibromatosis with CTNNB1 Oncogenic mutations: 2
Comments changed: Not TGA approved. FDA approved 27/11/2023. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.Not TGA approved. In DeFi Phase 3 trial, NCT03785964, Nirogacestat had a significant longer PFS over placebo (HR, 0.29). Subgroup analysis of biomarker selection showed both CTNNB1 and APC subgroups had HR of 0.28 and 0.20 respectively. Biomarker not required prospective specified in the eligiblity criteria.. (First curated: 2023-03-25)
Changed Talazoparib in Solid tumour except Breast cancer with ATM Oncogenic mutations (germline), Oncogenic mutations: R2
Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.. (First curated: 2023-11-27)
Changed Talazoparib in Solid tumour except Breast cancer with ATR Oncogenic mutation: R2
Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.. (First curated: 2023-11-27)
Changed Talazoparib in Solid tumour except Breast cancer with BRIP1 Oncogenic mutation: R2
Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.. (First curated: 2023-11-27)
Changed Talazoparib in Solid tumour except Breast cancer with CHEK2 Oncogenic mutation: R2
Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.. (First curated: 2023-11-27)
Changed Talazoparib in Solid tumour with PTEN Loss-of-function mutations, deletion: R2
Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.. (First curated: 2023-11-27)
Changed Talazoparib in Solid tumour except Breast cancer with RAD50 Oncogenic mutation: R2
Comments changed: Phase 2. NCT02401347. No responses were seen in solid tumour other than breast cancer with non-BRCA mutation in the HRD gene.. (First curated: 2023-11-27)

28 November, 2023 (Version: 20231128AU)

New Talazoparib in Solid tumour except Breast cancer with ATM Oncogenic mutations (germline), Oncogenic mutations: R2
References: 36253484
New Talazoparib in Solid tumour with PTEN Loss-of-function mutations, deletion: R2
References: 36253484
New Talazoparib in Solid tumour except Breast cancer with RAD50 Oncogenic mutation: R2
References: 36253484
New Talazoparib in Solid tumour except Breast cancer with BRIP1 Oncogenic mutation: R2
References: 36253484
New Talazoparib in Solid tumour except Breast cancer with CHEK2 Oncogenic mutation: R2
References: 36253484
New Talazoparib in Solid tumour except Breast cancer with ATR Oncogenic mutation: R2
References: 36253484
New Talazoparib in Breast cancer with PALB2 Oncogenic mutations (germline): 3
Phase 2. NCT02401347. PFS was 6.5 months (95% CI, 2.8-10.2) in patients with pretreated advanced HER2-negative breast cancer and other solid tumors with mutations in homologous recombination pathway genes other than BRCA1/2. In patients with breast cancer, overall response rate was 31% (4 partial responses), and clinical benefit rate was 54%. All patients with germline mutations in PALB2 had treatment-associated tumor regression. References: 36253484
New Apalutamide + Goserelin in Salivary gland cancers with AR Protein expression: 3
Phase 2. NCT04325828. AR-expressing SGC, pts treated with APA and GOS. ORR (6/24) was 25%. Clinical benefit rate and DCR were 50% and 70.8%, respectively. PFS and OS in the treated pts were 7.4 months and not reached, respectively. References: 10.1200/JCO.2022.40.16_suppl.6079

27 November, 2023 (Version: 20231127AU)

New Trastuzumab in Breast cancer with PTEN Loss-of-function mutations, deletion: R2
Preclinical study. Trastuzumab treatment increased the phosphatase activity of PTEN via Src inhibition. Patients with PTEN deficient breast cancers had significantly poorer responses to trastuzumab-based therapy than those with normal PTEN. References: 15324695

25 November, 2023 (Version: 20231125AU)

Changed Talazoparib in Acute myeloid leukaemia with PTEN : 4
Alterations changed: Loss-of-function mutations, deletion. (First curated: 2023-11-22)

22 November, 2023 (Version: 20231122AU)

New ELVN-002 in Solid tumour with ERBB2 Exon 20 insertion, A775_G776insYVMA, G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVCS310Y, R678Q, L755S, L755P, D769N, V773M, V777L, L869R, L869R and T798I, V842I: 4
Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019
New Tucatinib in Solid tumour with ERBB2 S310F, S310Y, R678Q, D769N, V773M, V777L, V842I, P780_Y781insGSP, V777_G778insGC: 4
Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019
New Tucatinib in Solid tumour with ERBB2 Exon 20 insertion, T798M, A775_G776insYVMA, G776delinsVC, G776_V777delinsLC, G776_V777delinsVV, G776_V777delinsCVC: R2
Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019
New ELVN-002 in Solid tumour with ERBB2 T798M: R2
Cell line study. Mutational drug sensitivity screen on transfected Ba/F3 cells. References: 10.1158/1538-7445.AM2023-4019
New Talazoparib in Acute myeloid leukaemia with PTEN Loss-of-function mutations: 4
References: 10.1182/blood-2021-146694

21 November, 2023 (Version: 20231121AU)

New Buparlisib in Glioblastoma with PIK3CA Oncogenic mutation: R2
Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months. References: 30715997
New Buparlisib in Glioblastoma with PIK3R1 Oncogenic mutation: R2
Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months. References: 30715997
New Buparlisib in Glioblastoma with PTEN Oncogenic mutations; Deletions; Loss of protein expression: R2
Phase 2 trial. NCT01968451. N=65. Patients with recurrent glioblastoma harboring PI3K pathway activation. Buparlisib had minimal single-agent efficacy in patients with PI3K-activated recurrent glioblastoma. PFS 1.6 months. References: 30715997

20 November, 2023 (Version: 20231120AU)

New FORE8394 in Solid tumour with BRAF V600, fusions: 3
Phase 1/2a FORE8394-201 study. NCT02428712. N=110. ORR in the treatment naive cohort was 39% (9/23); 18% (3/17) in previously treated with MAPKi. References: 10.1200/JCO.2023.41.16_suppl.3006
New KL590586 in Solid tumour with RET Fusions, Oncogenic mutations: 3
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%. References: 10.1200/JCO.2023.41.16_suppl.3007
New PRT811 in High-grade gliomas with IDH1 R132: 4
Phase 1 dose-expansion trial. NCT04089449. In IDH1/2-mutated glioma (n=16), PRT811 treatment was associated with 2 CR (1 durable) and 1 unconfirmed PR. References: 10.1200/JCO.2023.41.16_suppl.3008

17 November, 2023 (Version: 20231117AU)

New Repotrectinib in Non-small cell lung cancer with ROS1 Fusion: 2
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. References: 10.1200/JCO.2023.41.16_suppl.9017
Changed Vemurafenib in Erdheim-Chester disease, Langerhans Cell Histiocytosis with BRAF V600E: 2
Comments changed: Not TGA approved. Not PBS reimbursed. FDA approved. Secondary analysis of VE-BASKET study showed 62% confirmed ORR by RECIST and 100% PET response arte. PFS rate at 2 year was 86%.Not TGA approved. Not PBS reimbursed. Secondary analysis of VE-BASKET study showed 62% confirmed ORR by RECIST and 100% PET response arte. PFS rate at 2 year was 86%.. (First curated: 2020-05-15)
Changed Cobimetinib in Histiocytosis with BRAF V600E, N486_T491del: 2
Tier changed: 23. Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations.Signal of activity in phase 2 trial. (First curated: 2020-04-16)
Changed Cobimetinib in Histiocytosis with KRAS G12R, G13C, R149C: 2
Tier changed: 23. Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutationsPhase II Umbrella study. (First curated: 2020-04-16)
Changed Cobimetinib, Trametinib in Histiocytosis with MAP2K1 P142L, P124Q, Q56P, P105_107del: 2
Tier changed: 23. (First curated: 2020-04-16)
Changed Cobimetinib in Histiocytosis with MAP2K2 Oncogenic mutations, Y134H: 2
Tier changed: 23. (First curated: 2020-04-16)
Changed Cobimetinib in Histiocytosis with ARAF Oncogenic mutations, P216A: 4
Comments changed: Phase 2 trial. MEK inhibitor Cobimetinib was effective (ORR 89%) and durable in patients with histiocytoses regardless of genotype, including patients with ARAF, BRAF, RAF1, NRAS, KRAS, MAP2K1 and MAP2K2 mutations. No cases with isolated ARAF responded to cobimetinibOncoKB LOE 3; No cases with isolated ARAF responded to cobimetinib. (First curated: 2020-04-16)

14 November, 2023 (Version: 20231114AU)

New Osimertinib in Non-small cell lung cancer with EGFR Exon 19 deletion, L858R, Exon 21 mutation: 1B
Phase 3 FLAURA2 trial. NCT04035486. N=557. Combination of osimertinib with pemetrexed and a platinum agent led to significantly longer PFS over osimertinib monotherapy (19.3 v 11.2 months). ORR was similar between arms at 80% (osimertinib) and 84% (combination). References: 37937763
New Trastuzumab deruxtecan in Non-small cell lung cancer with ERBB2 Oncogenic mutation: 2
Phase 2 trial. DESTINY-Lung02. NCT04961073. N=152. Dose optimization study. Confirmed ORR was 49% (Median DOR 16.8 months) and 56% (NE) in T-DXd 5.4mg/kg and 6.4 mg/kg respectively. Grade ≥3 treatment related adverse events occurred in 38.6% and 58% of patients receiving 5.4 and 6.4 mg/kg, respectively. References: 37694347
New Tipifarnib in Head and neck squamous cell carcinoma with HRAS Oncogenic mutations, G12C, G12D, G12S, G13R, G13V: 3
Kura data set (NCT02383927) showed median DFS of 4.0 months (range 1-63 months, n=27), and OS of 25.5 months (range 4-94 month, n=27). Median OSmet was 15.0 months (range 1-47 months, n=27). MDACC data set showed median DFS of 4.0 months (n=12), and OS of 15 months (n=12). Median OSmet was 12 months (n=12). References: 36603172
New Ipatasertib in Solid tumour with AKT1 LAMTOR1-AKT1 fusion: 4
Case report. A paediatric patient with histopathologically indeterminate epithelioid neoplasm harbouring a novel fusion LAMTOR1-AKT1 treated with ipatasertib resulted in dramatic tumour regression. Confirmation in the in vitro models confirmed the fusion led to activation of AKT1. References: 30877085
New RMC-6236 in Pancreatic adenocarcinoma, Non-small cell lung cancer with KRAS G12, G12D, G12V, G12R, G12D, G12V, G12A: 4
Phase 1 trial. NCT04896732. N=33. in patients with KRASG12X, preliminary anti-tumor activity was seen with RMC-6236 pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Objective response rate was 36% (2 / 10 confirmed, 3 / 4 unconfirmed), median time to onset of initial response was 6 weeks, disease control rate was 86. References: 10.1016/j.annonc.2023.09.1838
New HRS-4642 in Solid tumour with KRAS G12D: 4
Phase 1 trial. NCT05597436. N=18. One NSCLC patient at 200 mg had PR, and 11/18 pts (61.1%) had SD with 33.3% experienced target lesion shrinkage. References: 10.1016/j.annonc.2023.10.025
New Palbociclib, Ribociclib in Solid tumour with CDK4 Amplification: R2
Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations. References: 37424386
New Palbociclib, Ribociclib in Solid tumour with CDK6 Amplification: R2
Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations. References: 37424386
New Palbociclib, Ribociclib in Solid tumour with CDKN2A Oncogenic mutations, deletions, Truncating mutations, Loss-of-function mutations: R2
Phase 2 DRUP/MoST trial. N=139. Palbociclib and ribociclib had a clinical benefit rate of 15% (0% ORR) in patients with advanced cancers with cyclin D-CDK4/6 pathway alterations. References: 37424386
New Tipifarnib in Salivary gland cancers, Salivary duct carcinoma, Epithelial-myoepithelial carcinoma with HRAS Oncogenic mutation; Q61R: R2
Phase 2. NCT02459813. N=13. Tipifarnib demonstrated a modest clinical activity in HRAS-mutant, R/M SGC with a DCR of 58%. One objective response was observed. 7 patients had SD as their best response. The median PFSwas 7 months. the median OS was 18 months. References: 32557577

29 October, 2023 (Version: 20231029AU)

New Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1B
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%). References: 37870955
New Selpercatinib in Non-small cell lung cancer with RET Fusion, KIF5B-RET fusion, CCDC6-RET fusion, NCOA4-RET fusion, KIF13A-RET fusion, KIAA1549L-RET fusion, KIAA1468-RET fusion, PRKAR1A-RET fusion: 1B
TGA approved. Not PBS reimbursed. Phase 3 trial. LIBRETTO-431. NCT04194944. N=261. Selpercatinib (1st line) improved PFS over chemoimmunotherapy (24.8 vs 11.2 months). ORR was similar between the two arms at 84% and 65%. The cause-specific hazard ratio for the time to CNS progression was 0.28. References: 37870973
New Amivantamab + Carboplatin + Pemetrexed in Non-small cell lung cancer with EGFR Exon 20 insertion: 2
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. References: 37870976
New Erdafitinib in Urothelial carcinoma with FGFR3 S249C, Y373C, R248C, G370C, Fusion, FGFR1-TACC3:fusion, FGFR1-TACC3:fusion_V1, FGFR1-TACC3:fusion_V3, FGFR3-BAIAP2L1 fusion: 2
Not TGA approved. FDA approved. Phase 3 trial. THOR. NCT03390504. In the subsequent line setting, Erdafitinib resulted in significantly longer overall survival than chemotherapy (12.1 months vs 7.8 months) among patients with metastatic urothelial carcinoma and FGFR alterations after previous anti-PD-1 or anti-PD-L1 treatment. ORR were 39% (Erdafitinib), versus 10% (Chemotherapy). References: 37870920
New Selpercatinib in Medullary thyroid cancer with RET Oncogenic mutation, M918T: 2
Not TGA approved. FDA approved. Phase 3 trial. LIBRETTO-531. NCT04211337. N=291. Selpercatinib had significantly longer PFS (HR, 0.28) and Treatment failure-free survival (HR, 0.25) compared to control group (cabozantinib or vandetanib) as first-line therapy in RET-mutant medullary thyroid cancer. ORR was 70% (cabozantinib/vandetanib: 39%). Adverse events led to dose reduction in 38.9% of the patients in selpercatinib group, as compared with 77.3% in the control group, and to treatment discontinuation in 4.7% and 26.8%, respectively. References: 37870969
New Tarlatamab in Small-cell lung cancer with DLL3 Protein expression: 3
Phase 2. DeLLphi-301. NCT05060016. N=220. In patients with previously treated extensive stage SCLC. Tarlatamab showed antitumor activity, with ORR of 32-40% across seen in different dose groups and durable objective responses (>6 months) in 40 of 68 (59%) patients. Note DLL3 expression was not required as per trial eligibility but ubiquitously expressed in SCLC. Objective responses were seen in patients with both positive, negative DLL3 expression. References: 37861218
Changed Tebentafusp in Uveal melanoma with HLA-A2 A*02:01: 1B
Tier changed: 1B2. Comments changed: 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%.Not TGA approved. FDA approved. 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 Selpercatinib in Non-small cell lung cancer with RET Fusions, ARHGAP12-RET fusion, CCDC6-RET fusion, CCDC88C-RET fusion, CLIP1-RET fusion, DOCK1-RET fusion, ERC1-RET fusion, KIF5B-RET fusion, NCOA4-RET fusion, PRKAR1A-RET fusion, RBPMS-RET fusion, RELCH-RET fusion, TRIM24-RET fusion: 1B
Tier changed: 1B2. Comments changed: TGA approved. Not PBS reimbursed. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%.Not TGA approved. FDA Approved 21/09/2022. LIBRETTO-001: First-line treatment. ORR 85%.. (First curated: 2020-05-08)

25 October, 2023 (Version: 20231025AU)

New Sotorasib + Panitumumab in Colorectal cancer with KRAS G12C: 2
Phase 3 trial. CodeBreaK 300. NCT05198934. N=160. Sotorasib + panitumumab showed longer progression-free survival (PFS) than standard treatment in chemorefractory metastatic colorectal cancer with mutated KRAS G12C. Median PFS: 5.6 months and 3.9 months for sotorasib at doses of 960 mg and 240 mg, respectively; 2.2 months for standard treatment (HR, 0.49 and 0.58, respectively). Overall survival data are maturing. Objective response rate: 26.4%, 5.7%, and 0% in the sotorasib-panitumumab groups and standard-care group, respectively. Treatment-related adverse events of grade 3 or higher occurred in 35.8%, 30.2%, and 43.1% of patients, respectively. References: 37870968
New AZD9574 in Solid tumour with BRCA1 Oncogenic mutations: 4
Preclinical study. PARP inhibitor (AZD9574) demonstrated potent anti-tumor activity and selectivity towards HRD+ models, showing dose-dependent efficacy in a BRCA1/2 mutant cell line, subcutaneous xenograft, and intracranial breast cancer brain metastases models. References: 10.1158/1538-7445.AM2022-2609
New AZD9574 in Solid tumour with BRCA2 Oncogenic mutations: 4
Preclinical study. PARP inhibitor (AZD9574) demonstrated potent anti-tumor activity and selectivity towards HRD+ models, showing dose-dependent efficacy in a BRCA1/2 mutant cell line, subcutaneous xenograft, and intracranial breast cancer brain metastases models. References: 10.1158/1538-7445.AM2022-2609
New Imatinib in Melanoma with CTNNB1+KIT CTNNB1:S33C and KIT:L576P: R2
Preclinical study. In a single patient case report, CTNNB1 mutation was identified in paired biopsy samples from a patient who had an initial response and later developed resistance to imatinib. Ba/F3 cell line model showed that the combination of KIT L576P mutation with CTNNB1 S33C mutation conferred acquired resistance to imatinib. References: 28421416

23 October, 2023 (Version: 20231023AU)

New Enzalutamide + Talazoparib in Prostate cancer with BRCA1 Oncogenic mutation: 2
NOT TGA approved. Phase 3 TALAPRO-2 trial. NCT03395197. N=805. Talazoparib plus enzalutamide significantly improved rPFS over placebo (not reached versus 21.9 months) in the first-line castrate-resistant setting. The benefit was observed in both HRR deficient and non-deficent groups, although significant higher HR reduction was seen in the BRCA1/2 deficient subgroup treated with Enzalutamide + Talazoparib. References: 37285865
New Enzalutamide + Talazoparib in Prostate cancer with BRCA2 Oncogenic mutation: 2
NOT TGA approved. Phase 3 TALAPRO-2 trial. NCT03395197. N=805. Talazoparib plus enzalutamide significantly improved rPFS over placebo (not reached versus 21.9 months) in the first-line castrate-resistant setting. The benefit was observed in both HRR deficient and non-deficent groups, although significant higher HR reduction was seen in the BRCA1/2 deficient subgroup treated with Enzalutamide + Talazoparib. References: 37285865

17 October, 2023 (Version: 20231017AU)

New Encorafenib + Binimetinib in Non-small cell lung cancer with BRAF V600E: 2
Not TGA approved. FDA approved. Phase 2, Open-Label Study of Encorafenib Plus Binimetinib in Patients With BRAFV600-Mutant Metastatic Non–Small-Cell Lung Cancer. NCT03148795. PHAROS. N=98. ORR was 75% (treatment naive) and 46% (previously treated). DCR after 24 weeks was 64% in treatment-naïve and 41% in previously treated patients. Median PFS was NE in treatment-naïve and 9.3 months in previously treated patients. References: 37270692
New PLX2853, PLX2853 + carboplatin in Ovarian Cancer with ARID1A Oncogenic mutation: R2
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. References: 37797273

11 October, 2023 (Version: 20231011AU)

New Rucaparib in Mesothelioma with BAP1 Loss of protein expression: 3
Phase 2 MiST. NCT03654833. Ten and 23 of 26 patients were BRCA1 and BAP1 protein expression negative, respectively. DCR at 12 week was 58%, and 23% at 24 weeks, meeting prespecified criteria. References: 33515503
New Vemurafenib + Obinutuzumab in Hairy cell leukaemia with BRAF V600E: 3
Phase 2. NCT03410875. N=30. Vemurafenib plus obinutuzumab achieved CR in more than 90% of patients with previously untreated HCL. Acquired vemurafenib resistance or dose-limiting toxicity was not observed in this small study. References: 10.1056/EVIDoa2300074
New Rucaparib in Mesothelioma with BRCA1 Loss of protein expression: 3
Phase 2 MiST. NCT03654833. 10 and 23 of 26 patients were BRCA1 and BAP1 protein expression negative, respectively. DCR at 12 week was 58%, and 23% at 24 weeks, meeting prespecified criteria. References: 33515503
New ARV-471 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
Phase 1/2 study (VERITAC). NCT04072952. In ARV-471 monotherapy for ER+/HER2- metastatic breast cancer, CBR was 40% at 24 weeks and independent of ESR1 mutation (including 3 PR). All patients received prior CDK4/6 inhibitors, and majority received prior fulvestrant and prior chemotherapy. References: 10.1158/1538-7445.SABCS22-GS3-03

02 October, 2023 (Version: 20231002AU)

New Olaparib + Durvalumab in Solid tumours with ATM Oncogenic mutation: 3
Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 38% and ORR was 3 /32 (9%) non-BRCA-mutated groups. Only responders were seen in patients with ATM mutations. References: 37365284
New Olaparib + Durvalumab in Solid tumours with BRCA2 Oncogenic mutation: 3
Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 35% and ORR was 3 /16 (19%) BRCA-mutated groups. All responders harboured BRCA2 mutations. References: 37365284
New Olaparib + Durvalumab in Solid tumours with BRCA1 Oncogenic mutation: 4
Phase 2 Basket trial. ACTRN12617001000392. PFS6 rate was 35% and ORR was 3 /16 (19%) BRCA-mutated groups, although no responders were seen in 4 patients with BRCA1 mutations. References: 37365284

27 September, 2023 (Version: 20230927AU)

New Oxaliplatin, Cisplatin in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 4
References: 35135099
New Oxaliplatin, Cisplatin in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 4
References: 35135099
Changed Dabrafenib + Trametinib in High-grade gliomas with BRAF V600: 2
Tier changed: 23. References changed: 37643378, 10.1200/JCO.2022.40.16_suppl.2009. (First curated: 2022-06-20)
Changed Dabrafenib + Trametinib in Low-grade gliomas with BRAF V600: 2
Tier changed: 23. References changed: 10.1056/NEJMoa2303815, 10.1200/JCO.2022.40.17_suppl.LBA2002. (First curated: 2021-06-20)

15 September, 2023 (Version: 20230915AU)

New Talazoparib + VX-970 in Prostate cancer with TP53+RB1 TP53:Oncogenic mutations AND RB1:Oncogenic mutations, TP53:Oncogenic mutations AND RB1:Deletion: 4
Cell line study. Prostate cancers with TP53 and RB1 loss may be associated with poor outcomes, stem-like properties, and may exhibit loss of AR activity. TP53/RB1 mutants are sensitive to PARP and ATR inhibition in cell-line models. References: 32460015
Changed Nimotuzumab + Gemcitabine in Pancreatic adenocarcinoma with KRAS NOT oncogenic mutations: 2
References changed: 37647576; 10.1200/JCO.2022.40.17_suppl.LBA4011. (First curated: 2022-06-06)
Changed ABBV-400 with MET Overexpression: 4
Cancer type(s) changed: Non-small cell lung cancer, Gastroesophageal junction adenocarcinoma, Gastric Cancer, Endometrial carcinoma, Acral melanomaNon-small cell lung cancer, Gastroesophageal junction adenocarcinoma, Gastric Cancer, Endometrial carcinoma, Arcal melanoma (First curated: 2023-09-09)

13 September, 2023 (Version: 20230913AU)

New Lenvatinib + Pembrolizumab in Endometrial cancer with Mismatch repair Deficient: 1
PBS reimbursed. TGA approved. FDA Approved. In KEYNOTE-775, median PFS was 10.7 v 3.7 months and OS was not reached vs 8.6 months for dMMR population. Note Benefits were seen in both pMMR and dMMR populations, and the TGA approval was irrespective of MMR status. References: 30922731, 32167863
New Pemigatinib in Glioblastoma, Cervical cancer with FGFR3 Fusion: 3
Phase 2. NCT03822117. FIGHT-207. In the fusion cohort (Cohort A), ORR was 27%. In the activating mutation cohort (Cohort B), ORR was 9%. References: 10.1158/1538-7445.AM2023-CT016
New ABBV-400 in Non-small cell lung cancer, Gastroesophageal junction adenocarcinoma, Gastric Cancer, Endometrial carcinoma, Arcal melanoma with MET Overexpression: 4
Phase 2. NCT05029882. Clinical activity was observed with ABBV-400 with an ORR of 24% (11/45). All responses were confirmed partial responses. DCR was 81%. Overexpression was determined IHC. References: 10.1200/JCO.2023.41.16_suppl.3015
New Larotrectinib in Low-grade spindle cell neoplasm, Solid tumour with BRAF BRAF-CREB3L2 rearrangement, amplification: R2
Case report. References: 37666486
New Palbociclib in Solid tumour except Breast cancer with CCND1 Amplification: R2
Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months. References: 36853016
New Palbociclib in Solid tumour except Breast cancer with CCND2 Amplification: R2
Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months. References: 36853016
New Palbociclib in Solid tumour except Breast cancer with CCND3 Amplification: R2
Phase 2 NCI-MATCH trial Z1B. NCT05648716. In solid tumor patients with CCND1, 2, or 3 amplifications, there were no partial response, the best response was stable disease (n=12), median PFS 1.8 months. References: 36853016
New Larotrectinib in Low-grade glioma, Low-grade spindle cell neoplasm, Solid tumour with CDKN2A Deletion: R2
Case reports. References: 37666486
New Larotrectinib in Low-grade glioma with EGFR Amplification: R2
Case report. References: 37666486
Changed Lenvatinib + Pembrolizumab in Endometrial cancer with Microsatellite instability+Mismatch repair NOT Microsatellite instability:high AND NOT Mismatch repair:deficient: 1
Tier changed: 1B. Comments changed: PBS reimbursed. TGA approved. FDA Approved. In KEYNOTE-146: ORR was 38% (out of 94 patients) including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS). In the confirmatory trial (KEYNOTE-775), primary point was met in non-MSI-H/dMMR patients who have progressed through one previous line of platinum-based chemotherapy: median PFS was 6.6 (pembrolizumab + lenvatinib) vs 3.8 months (investigator choice of chemotherapy) and median OS: 17.4 vs 12 months (chemotherapy). ORR: 30% vs 15%. Note Benefits were seen in both pMMR and dMMR populations, and the TGA approval was irrespective of MMR status.TGA provisional approval. FDA Approved. In KEYNOTE-146: ORR was 38% (out of 94 patients) including 10 CR. Note that ORR was higher for MSI-H at 64% at week 24, (vs. 36% in MSS). In the confirmatory trial (KEYNOTE-775), primary point was met in non-MSI-H/dMMR patients who have progressed through one previous line of platinum-based chemotherapy: median PFS was 6.6 (pembrolizumab + lenvatinib) vs 3.8 months (investigator choice of chemotherapy) and median OS: 17.4 vs 12 months (chemotherapy). ORR: 30% vs 15%.. (First curated: 2020-12-11)
Changed Pemigatinib: 3
Cancer type(s) changed: Glioblastoma, Diffuse astrocytoma, Cervical cancer Biomarker changed: FGFR1FGFR3. Alterations changed: Fusion; K656E. (First curated: 2023-05-05)

08 September, 2023 (Version: 20230908AU)

New Savolitinib in Gastroesophageal junction adenocarcinoma, Gastric Cancer with MET Amplification: 2
Not TGA approved. Not FDA approved. Phase 2. NCT04923932. Savolitinib monotherapy showed ORR of 45% in MET-amplified gastric cancer or gastro-oesophageal junction adenocarcinoma especially in those with high MET gene copy number. DOR rate at 4-month was 86%. References: 10.1158/1538-7445.AM2023-CT152
New Volasertib, AZD7762 in Triple-negative breast cancer with RB1 Oncogenic mutations: 4
References: 29386107

05 September, 2023 (Version: 20230905AU)

New Afatinib, Poziotinib, Poziotinib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with ERBB2 R188C, P489L, L1157R: 4
References: 32366937
New Gefitinib, Erloginib, Lapatinib, Canertinib, Pelitinib in Acute myeloid leukaemia, Acute lymphoblastic leukaemia with ERBB2 R188C, P489L, L1157R: 4
References: 32366937

04 September, 2023 (Version: 20230904AU)

New SN-38 + VE-822 in Colorectal adenocarcinoma with ATR Oncogenic mutation: 4
Cell line study. Heterozygous mutation in ATR renders the cells more susceptible to SN-38 and ATR inhibition, resulting in resulting in DNA damage, depletion of RPA. Consequently, leading to replication catastrophe. References: 35361811
New Patritumab deruxtecan in Breast cancer with ERBB3 V104M, A232V, P262H, G284R, Q809R, S846I, E928G: 4
Cell line study. Patritumab deruxtecan demonstrated in vitro activity against breast cancer cell line transduced to expressmutated HER3. References: 35503762
New ONC201 + Paxalisib in Diffuse Midline Glioma with H3F3A K27M, K28M: 4
Case reports. ONC201 + Paxalisib in two DIPG patients with H3.1K27M and H3.3K27M altered midline glioma.]. References: 37145169
New ONC201 in Diffuse Midline Glioma with TP53 Oncogenic mutation: R2
Drug screening. Reduced sensitivity to ONC201 was found in DIPG cell lines harbouring TP53 mutantion. References: 37145169
Changed Rucaparib in Ovarian cancer with BRCA2 Oncogenic mutations: 2
References changed: 3565848710.1200/JCO.22.01003. (First curated: 2022-06-06)
Changed Rucaparib in Ovarian cancer with Homologous Recombination Deficiency Score High: 2
References changed: 3565848710.1200/JCO.22.01003. (First curated: 2022-06-06)
Changed Lapatinib in Glioblastoma with PTEN Loss of protein expression: R2
Comments changed: Phase 1/2 trial. Lapatinib. Recurrent GBM. ORR 0%.. (First curated: 2022-02-23)

24 August, 2023 (Version: 20230824AU)

New Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with KRAS G12C: 3
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. N=137 (NSCLC=60, Colorectal cancer =55, other solid tumors=22). ORR in NSCLC was 53% with PFS: 13.1 months. ORR in CRC was 29% with PFS of 5.6 months. Responses also seen in other solid tumors. References: 37611121
New LY3410738 in Cholangiocarcinoma with IDH1 R132C+D279N: 4
Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib related to the treatment-emergent D279N mutation showed sensitivity to LY3410738. References: 36056177
New Divarasib in Colorectal adenocarcinoma with ALK EML4-ALK fusion: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Colorectal adenocarcinoma, Solid tumours with BRAF G469A, L597Q, L597R, V600E, K601E: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Colorectal adenocarcinoma with ERBB2 Amplification: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Ivosidenib in Cholangiocarcinoma with IDH1 D279N: R2
Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib is related to the treatment-emergent D279N mutation, where the double mutant showed impaired binding to ivosidenib despite reduced efficiency in producing 2HG. References: 36056177
New Ivosidenib in Cholangiocarcinoma with IDH2 R172K: R2
Case report and preclinical study. In a case of IDH1 R132C cholangiocarcinoma, acquired resistance to ivosidenib is related to the treatment-emergent IDH2 R172 mutation. References: 36056177
New Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with KRAS Amplification, G12A, G12D, G12R, G12V, G13D, R68S, H95R, Y96D, Y96H, Y96N, Q99L, A146T, Oncogenic mutation AND NOT G12C: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Non-small cell lung cancer, Colorectal adenocarcinoma, Solid tumours with MAP2K1 Q56P, K57N, E203K: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Colorectal adenocarcinoma with NRAS G13R: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Colorectal adenocarcinoma with PIK3CA E545K: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Solid tumours with PTEN Deletion: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
New Divarasib in Solid tumours with RB1 Deletion: R2
Phase 1/2 single arm trial. GO42144. Divarasib. NCT04449874. Acquired and treatment-emergent mutations. References: 37611121
Changed Niraparib + Abiraterone Acetate in Prostate cancer with BRCA1 Oncogenic mutations: 2
References changed: 3695263436952642. (First curated: 2023-03-29)
Changed Niraparib + Abiraterone Acetate in Prostate cancer with BRCA2 Oncogenic mutations: 2
References changed: 3695263436952642. (First curated: 2023-03-29)
Changed Therapy in Colorectal cancer with KRAS G12C: 4
Therapy changed: Divarasib + CetuximabGDC-6036 + Cetuximab. (First curated: 2023-05-05)
Changed Sonidegib, Vismodegib in Solid tumours with BRAF V600E: R2
(First curated: 2020-07-200202-07-020)

15 August, 2023 (Version: 20230815AU)

Changed Olaparib in Pancreatic adenocarcinoma with BRCA1 Oncogenic mutations (germline): 1B
References changed: 31157963, 35834777. (First curated: 2020-04-25)
Changed Olaparib in Pancreatic adenocarcinoma with BRCA2 Oncogenic mutations (germline): 1B
References changed: 31157963, 35834777. (First curated: 2020-04-25)

14 August, 2023 (Version: 20230814AU)

Removed Atezolizumab in Urothelial carcinoma with TP53+RB1 alterations TP53:Oncogenic mutations AND RB1:Oncogenic mutations, TP53:Oncogenic mutations AND RB1:Deletion: Tier 4   (First curated: 2023-06-14)

10 August, 2023 (Version: 20230810AU)

New Alectinib in Prostate small cell carcinoma with ALK F1174C: 4
Case report. In one case of prostate small cell carcinoma harbouring ALK F1174C, Alectinib led to stable disease for more than 6 months, improved symptoms, and in ctDNA vaf. References: 29559559