RMC-6291 is an orally active and covalent inhibitor of KRAS G12C (ON) . RMC-6291 forms a tri-complex within tumor cells between KRAS G12C (ON) and cyclophilin A (CypA). Thus, RMC-6291 prevents KRAS G12C (ON) from signaling via steric blockade of RAS effector binding. RMC-6291 inhibits ERK signaling and induced apoptosis in KRASG12C-mutant H358 cells. RMC-6291 also inhibits the proliferation of KRAS G12C mutant cells with a median IC 50 of 0.11 nM .