Table 3 KRASG12C inhibitors in phase 1/2 clinical trials
From: RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms
Phase | KRAS inhibitor | Trial details | Tumor type and No. of patients | Reported data |
|---|---|---|---|---|
1/2 | Sotorasib (OFF state inhibitor) | CodeBreaK 100 NCT03600883 | NSCLC (n = 174) (131) | ORR: 37.1%; DCR: 80.6%; mPFS: 6.8 mo; mOS: 12.5 mo |
CRC (n = 62) (132) | ORR: 9.7%; DCR: 82.3%; mPFS: 4.0 mo; mOS: 10.6 mo | |||
PDAC (n = 38) (18) | ORR: 21%; DCR: 84%; mPFS: 4.0 mo; mOS: 6.9 mo | |||
1/2 | Adagrasib (OFF state inhibitor) | KRYSTAL-1 NCT03785249 | NSCLC (n = 116) (16) | ORR: 42.9%; DCR: 50.5%; mPFS: 6.5 mo; mOS:12.6 mo |
CRC (n = 44 for adagrasib; 32 for adagrasib + cetuximab) (153) | Adagrasib ORR: 19%; mPFS: 5.6 mo; mOS: 19.8 mo Adagrasib + cetuximab ORR: 46%; mPFS: 6.9 mo; mOS: 13.4 mo: | |||
PDAC (n = 21); biliary tract cancers (n = 12) (133) | PDAC ORR: 33.3%; mPFS: 5.4 mo; mOS: 8.0 mo biliary tract cancers ORR: 41.7%; mPFS: 8.6 mo; mOS: 15.1 mo | |||
1 | Divarasib (OFF state inhibitor) | NCT04449874 | NSCLC (n = 60); CRC (n = 55); PDAC (n = 7) (134) | NSCLC ORR: 53.4%; mPFS: 13.1 mo CRC ORR: 29.1%; mPFS: 5.6 mo PDAC ORR: 42.8% |
1b | Divarasib + cetuximab | NCT04449874 | CRC (n = 24 for KRASi-naive patients; n = 5 for Prior KRAS G12Ci) (154) | KRASi-naive patients ORR: 62.5%; mPFS: 8.1 mo Prior KRAS G12Ci 3 (60.0%)–PR; 2 (40.0%)–SD |
1 | Olomorasib (LY3537982; Eli Lilly) (OFF state inhibitor) | NCT04956640 | NSCLC (n = 14); CRC (n = 32); PDAC(12) (n = 24); Other solid tumors (n = 11) (12) | NSCLC KRAS G12Ci naive: ORR 60% KRAS G12Ci treated: ORR 0% CRC ORR 9% PDAC ORR: 42% Other solid tumors ORR 36% |
1/2 | Opnurasib (JDQ443; Novartis) (OFF state inhibitor) | KontRASt-01 NCT04699188 | NSCLC (n = 24) (12) | ORR 42% |
1/2 | Glecarisib (JAB-21822; Jacobio Pharma) (OFF state inhibitor) | NCT05002270 | CRC (n = 33); PDAC (n = 31) (12) | CRC ORR 33.3% PDAC ORR 42% |
2 | IBI351 (Innovent Tech) (OFF state inhibitor) | NCT05005234 NCT05497336 | NSCLC (n = 116); CRC (n = 40) (12) | NSCLC ORR: 46.6%; mPFS: 8.3 mo CRC ORR: 47.5% |
1/2 | Garsorasib (D-1553 InventisBio) (OFF state inhibitor) | NCT04585035 | NSCLC (n = 74); CRC (n = 20) (12) | NSCLC ORR: 40.5% mPFS: 8.2 mo CRC ORR: 20.8%; mPFS: 7.6 mo |
1 | D3S-001 (D3 Bio) (OFF state inhibitor) | NCT05410145 | No data | No data |
1/2 | FMC-376 (Frontier Medicines) ON/OFF state direct inhibitor | NCT06244771 | No data | No data |
1 | RMC-6291 (Revolution Medicines) (On state inhibitor) | NCT05462717 | NSCLC (n = 17); CRC (n = 20) (12) | NSCLC KRASi G12Ci naive: ORR 43%; KRASi treated: ORR 50% CRC ORR 40% |