Divarasib — Investigational Agent
KRAS Inhibitor · Phase 2 · Genentech / Roche
Mechanism of Action
Divarasib is a highly potent and selective covalent inhibitor of KRAS G12C. It binds to the switch II pocket of the inactive GDP-bound form of KRAS G12C with high affinity. Divarasib is designed to be significantly more potent than first-generation inhibitors (sotorasib and adagrasib) in preclinical models, achieving more complete and sustained inhibition of KRAS signaling. By locking KRAS G12C in its inactive state, it suppresses the MAPK pathway and triggers apoptosis in cells harboring the G12C mutation.
Investigational Indications
- KRAS G12C-mutant non-small cell lung cancer
- KRAS G12C-mutant colorectal cancer
- Advanced solid tumors with KRAS G12C mutation