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 |