Table 4.
Selected examples of ongoing large genotype–drug matching PCM trials
| Name | Site | Sample size | Mutations matched | Targeted drugs used |
|---|---|---|---|---|
| NCI-MATCH [165] | National Cancer Institute (NCI) | 6452 | EGFR/HER2-activating mutation | Afatinib |
| MET, ALK, ROS1 | Crizotinib | |||
| EGFR T790M or other activating mutation | Osimertinib | |||
| BRAF V600E/R/K/D, BRAF fusion, non-BRAF V600 mutations | Dabrafenib+trametinib | |||
| NF1, GNAQ, GNA11 | Trametinib | |||
| PIK3CA | Taselisib | |||
| HER-2 amplification | Trastuzumab+pertuzumab | |||
| FGFR mutation or fusion | Erdafitinib | |||
| mTOR, TSC1, TSC2 | Sapanisertib | |||
| PTEN mutation | GSK2636771 (PI3K beta inhibitor) | |||
| HER-2 amplification | Trastuzumab, emtansine | |||
| SMO, PTCH1 | Vismodegib | |||
| NF2 inactivating mutation | Defactinib | |||
| cKIT mutation | Sunitinib | |||
| FGFR1, FGFR2, FGFR3 mutation | AZD4547 (FGFR inhibitor) | |||
| Certain DDR2 mutations | Dasatinib | |||
| AKT mutation | Capivasertib | |||
| NRAS mutations | Binimetinib | |||
| CDK4, CDK6 | Palbociclib | |||
| Mismatch repair deficiency | Nivolumab | |||
| NTRK1, NTRK2, NTRK3 fusions | Larotrectinib | |||
| PIK3CA, PTEN mutations | Copanlisib | |||
| BRCA1, BRCA2 mutation | Adavosertib | |||
| AKT mutation | Ipatasertib | |||
| BRAF non-V600 mutation or BRAF fusion | Ulixertinib | |||
| TAPUR [166] | American Society of Clinical Oncology (ASCO) | 3123 | ALK, ROS1, MET | Crizotinib |
| CDKN2A, CDK4, CDK6 | Palbociclib | |||
| CSF1R, PDGFR, VEGFR | Sunitinib | |||
| mTOR, TSC | Temsirolimus | |||
| ERBB2 | Trastuzumab+pertuzumab | |||
| BRAFV600E/D/K/R | Vemurafenib+cobimetinib | |||
| NRAS, KRAS, NRAF | Cetuximab | |||
| BCR-ABL, SRC, KIT, PDGFRB, EPHA2, FYN, LCK, YES1 | Dasatinib | |||
| RET, VEGFR1/2/3, KIT, PDGFRB, RAF-1, BRAF | Regorafenib | |||
| BRCA1, BRCA2, ATM | Olaparib | |||
| POLE, POLD1, high mutational load | Pembrolizumab | |||
| MSI-high, high mutational load and others | Nivolumab+ipilimumab | |||
| CAPTUR [162] | Canadian Cancer Trials Group (CCTG) | 720 | VEGFR1, VEGFR2, VEGFR2 | Axitinib |
| BCR-ABL, SRC | Bosutinib | |||
| ALK, ROS1, MET | Crizotinib | |||
| KIT, PDGRFA, PDGFRB, ABL1 | Dasatinib | |||
| EGFR | Erlotinib | |||
| High mutation burden, POLE, POLD1 | Nivolumab+ipilimumab | |||
| BRCA1, BRCA2, mutations in HRD | Olaparib | |||
| CDKN2A, CDK4, CDK6, CCND1 | Palbociclib | |||
| CSF1R, PDGFRA, PDGFRB, VEGFR1, VEGFR2, VEGFR3, KIT, FLT3, RET, FGFR1, FGFR2, FGFR3, VHL | Sunitinib | |||
| AKT1, AKT2, AKT3, FBXW7, FLCN, mTOR, NF1, NF2, NTRK3, PIK3CA, PIK3R1, PTEN, RHEB, STKII, TSC1, TSC2 | Temsirolimus | |||
| ERBB2 | Trastuzumab+pertuzumab | |||
| BRAFV600 | Vemurafenib+cobimetinib | |||
| PTCH1, SMO | Vismodegib | |||
| DRUP [167] | Netherlands Cancer Institute | 400 | KRAS, BRAF, NRAS wild type | Panitimumab |
| BRCA1, BRCA2, ATM | Olaparib | |||
| BRAF | Dabrafenib | |||
| Molecular profile that can potentially be targeted by nilotinib | Nilotinib | |||
| Molecular profile that can potentially be targeted by trametinib | Trametinib | |||
| Molecular profile that can potentially be targeted by erlotinib | Erlotinib | |||
| HER-2 overexpression, amplification or mutated | Trastuzumab+pertuzumab | |||
| BRAF mutated tumors | Vemurafenib+cobimetinib | |||
| Molecular profile that can potentially be targeted by vismodegib | Vismodegib | |||
| Molecular profile that can potentially be targeted by regorafenib | Regorafenib | |||
| Molecular profile that can potentially be targeted by nivolumab | Nivolumab |