Main clinical trials evaluating key site-specific targeted drugs in CRC treatment
| Trial | Targeted gene variations | Treatment regimen | Target population | Outcomes |
|---|---|---|---|---|
| Recommended by guidelines | ||||
| BEACON | BRAF p.V600E | Encorafenib + cetuximab | mCRC with BRAF p.V600E mutation | mOS 9.3 months, ORR 19.5% |
| Encorafenib + cetuximab + binimetinib | mOS 9.3 months, ORR 26.8% | |||
| SWOG S1406 | BRAF p.V600E | Vemurafenib + cetuximab + irinotecan | mCRC with BRAF p.V600E mutation | ORR 17%, DCR 65% |
| MyPathway | HER2 amplification | Trastuzumab + pertuzumab | HER2-amplified mCRC | ORR 32% |
| DESTINY-CRC01 | HER2 amplification | Trastuzumab deruxtecan (DS8201) | HER2-positive mCRC, immunohistochemistry (IHC) 3+ or IHC2+ and in-situ hybridization (ISH)-positive | ORR 45.3% |
| NAVIGATE | NTRK fusion | Larotrectinib | CRC with NTRK gene fusion | mPFS 5.3 months, mOS 33.4 months |
| CONCUR | Multiple kinases (including VEGF receptors, fibroblast growth factor receptors, platelet-derived growth factor receptors, BRAF, KIT, and RET) | Regorafenib | Refractory progressive mCRC | mOS 8.8 months vs. 6.3 months |
| Potential and ongoing | ||||
| Hong 2020 | KRAS p.G12C | Sotorasib (AMG-510) | CRC with KRAS p.G12C mutation | ORR 7.1%, DCR 73.8%, mPFS 4.0 months |
| KRYSTAL-1 | KRAS p.G12C | Adagrasib | CRC with KRAS p.G12C mutation | ORR 22%, DCR 87%, mPFS 5.6 months |
| Adagrasib + cetuximab | ORR 43%, DCR 100% | |||
| NCT05737706 | KRAS p.G12D | MRTX1133 | CRC with KRAS p.G12D mutation | Status: recruiting |
| AMPLIFY-201 | KRAS G12D, KRAS G12R | ELI-002 2P | CRC with KRAS/NRAS p.G12D or p.G12R mutation | Status: active, not recruiting |
| NCT04627142 | pan-KRAS | BI 1701963 | mCRC with confirmed KRAS mutations | Status: terminated |
| STARTRK-2 | NTRK1/2/3 | Entrectinib (RXDX-101) | mCRC with NTRK1/2/3-rearrangement (fusion) | Status: active, not recruiting |
DCR, disease control rate; mPFS, median progression-free survival; mOS, median overall survival; ORR, objective response rate.