Table 1. Main studies assessing KRAS G12C inhibitors in human solid tumors as monotherapy.
| KRAS G12C inhibitor agent | Clinical trial | Cancer types | Main results |
|---|---|---|---|
| AMG-510 (sotorasib, 960 mg once daily) | Phase I/II (CodeBreaK 100, NCT03600883) (n=129) (6,8) | Advanced solid tumors | |
| NSCLC (n=59) | Partial response: 37.1%, median PFS: 6.8 months | ||
| CRC (n=42) | Partial response: 9.7%, median PFS: 4.0 months | ||
| Pooled phase I/II (CodeBreaK 100, NCT03600883) (6) | PDAC (n=38) | Partial response: 21%, median PFS: 4.0 months | |
| Phase III (CodeBreaK 200, NCT04303780) (7) | Advanced NSCLC, compared to docetaxel (≥ L2) (n=116) | Median PFS: 5.6 vs. 4.0 months, P<0.05 | |
| MRTX849 (adagrasib, 600 mg twice daily) | Phase I/II (KRYSTAL-1, NCT03785249 (9) | Advanced solid tumors | |
| NSCLC (n=116) | Partial response: 42.0%, median PFS: 6.5 months | ||
| Locally advanced or mCRC (n=44) | Objective response rate: 22%, median PFS: 5.6 months | ||
| Phase III (KRYSTAL-12, NCT04685135) | Advanced NSCLC, compared to docetaxel (≥ L2) | Ongoing | |
| D-1553 (600 or 800 mg twice daily) | Phase I/II (NCT04585035) | Locally advanced or mCRC (n=24) | Objective response rate: 20.8%, median PFS: 7.62 months |
| GDC-6036 (divarasib, 400 mg once daily) | Phase I (NCT04449874) | Advanced solid tumors | |
| NSCLC (n=60) | Objective response rate: 53.4%, median PFS: 13.1 months | ||
| Locally advanced or mCRC (n=55) | Objective response rate: 29.1%, median PFS: 5.6 months | ||
| JNG-74699157 | Phase I (NCT04006301) (n=10) | Advanced solid tumors | No significant clinical benefit |
| LY3499446 | Phase I (NCT04165031) (n=5) | Advanced solid tumors | The study was early stopped due to an unexpected high rate of toxicities |
NSCLC, non-small cell lung carcinoma; PFS, progression-free survival; CRC, colorectal cancer; PDAC, pancreatic ductal adenocarcinoma; mCRC, metastatic CRC.