LBA6 KRYSTAL-1: Adagrasib (MRTX849) as monotherapy or combined with cetuximab (Cetux) in patients (Pts) with colorectal cancer (CRC) harboring a KRASG12C mutation

Abstract

KRASG12C mutations, which occur in 3%-4% of CRC, are a negative predictor of cetux efficacy. Adagrasib, an investigational agent, is a KRASG12C inhibitor that irreversibly and selectively binds KRASG12C, locking it in its inactive state; it was optimized for favorable PK properties, including a long half-life (∼24 hours). Durable inhibition of KRASG12C may be particularly important in CRC due to signaling pathways which create a susceptibility to feedback reactivation of KRAS. EGFR signaling is implicated in this reactivation, providing a rational co-targeting strategy for KRAS-mutant CRC.