Table 2.
Clinical development of strategies to target KRAS in cancer
| Agent | Target | Clinical trial number (Clinicaltrials.gov) | Remarks |
|---|---|---|---|
| Sotorasib (AMG-510) | Direct mutant KRAS G12C covalent inhibitor |
NCT03600883
NCT04185883 NCT04933695 NCT04303780 |
Sotorasib obtained accelerated FDA approval. Ongoing phase Ib, II, and III trials for patients with G12C mutations. |
| MRTX849 | Direct mutant KRAS G12C covalent inhibitor |
NCT04330664, NCT03785249 NCT04685135 NCT04793958 NCT04613596 |
KRYSTAL trials: Phase I/II trials for patients with G12C mutations. Phases II and III trials for NSCLC and CRC patients with G12C mutations. |
| LY3499446 | Direct mutant KRAS G12C covalent inhibitor | NCT04165031 | Trial terminated due to unanticipated toxicities. |
| JNJ-74699157 | Direct mutant KRAS G12C inhibitor | NCT04006301 | Trial completed, no results reported |
| GDC 6036 | Direct mutant KRAS G12C inhibitor | NCT04449874 | Phase I trial for tumors with G12C mutations. |
| D-1553 | Direct mutant KRAS G12C inhibitor | NCT04585035 | Phase I/II trial for tumors with G12C mutations. |
| BI-1701963 | SOS1 inhibitor | NCT04111458 | Phase I trial for solid KRAS mutated tumors. |
| RMC-4630 | SHP2 inhibitor |
NCT03634982
NCT04916236 |
Phase I/Ib trial for tumors with MAPK pathway hyperactivation, including KRAS mutated. |
| TNO155 | SHP2 inhibitor |
NCT04000529
NCT03114319 NCT04330664 |
Phase I and II trials |
| ERAS-601 | SHP2 inhibitor | NCT04670679 | FLAGSHP-1 phase I/Ib trial in advanced or metastatic solid tumors as a single agent or in combination with MEK inhibitor |
| JAB-3312 | SHP2 inhibitor |
NCT04045496
NCT04720976 NCT04121286 |
Phase I/IIa clinical trials for patients with solid tumors |
| BBP-398 | SHP2 inhibitor | NCT04528836 | Phase I trial for patients with advanced solid tumors |
| RLY-1971 | SHP2 inhibitor | NCT04252339 | Phase I trial for patients with advanced solid tumors. However, it excludes patients with KRAS G12D, G12V, G13X, and Q61X mutations. |
| mRNA-5671/V941 | Mutant KRAS mRNA vaccine | NCT03948763 | Phase I trial for KRAS mutated solid tumors |
| KRAS peptide vaccine | Mutant KRAS long peptide vaccine | NCT04117087 | Phase I trial in CRC and PDAC |
| mDC3/8-KRAS Vaccine | Dendritic cell vaccine | NCT03592888 | Phase I trial in KRAS mutated resectable PDAC |
| Anti-KRAS G12D/G12V mTCR PBL | Adoptive cell transfer |
NCT03745326
NCT03190941 |
Trials have been suspended. |
CRC colorectal carcinoma, FDA food and drug administration, mTCR PBL murine T-cell receptor transduced peripheral blood lymphocytes, PDAC pancreatic ductal adenocarcinoma