Olomorasib — Investigational Agent
KRAS Inhibitor · Phase 3 · Eli Lilly and Company
Mechanism of Action
Olomorasib is a potent, orally bioavailable, second-generation covalent inhibitor of KRAS G12C. It forms an irreversible covalent bond with the mutant cysteine-12 residue in the switch-II pocket, selectively trapping KRAS G12C in its inactive GDP-bound state and abrogating downstream RAS-MAPK (RAF-MEK-ERK) signaling. Compared with first-generation agents (sotorasib, adagrasib), olomorasib has higher potency and a longer target residence time, which may improve depth of target engagement and activity against tumors that have acquired resistance to earlier G12C inhibitors. It has no meaningful…
Investigational Indications
- KRAS G12C-mutant non-small cell lung cancer (NSCLC), including as first-line therapy with pembrolizumab
- KRAS G12C-mutant colorectal cancer (CRC), including combinations with anti-EGFR antibodies
- Other KRAS G12C-mutant advanced solid tumors