sotorasib + adagrasib

**Sotorasib + adagrasib** is a combination of two small-molecule KRAS G12C inhibitors investigated for potential synergistic effects in treating cancers driven by the KRAS G12C mutation, particularly non-small cell lung cancer (NSCLC). Sotorasib (Lumakras), developed by Amgen, and adagrasib (Krazati), developed by Mirati Therapeutics (acquired by Bristol Myers Squibb), are both FDA-approved as monotherapies for KRAS G12C-mutated advanced NSCLC after prior systemic therapy, covalently binding to the inactive GDP-bound form of KRAS G12C to lock it in an inactive state, preventing downstream RAF-MEK-ERK signaling activation that promotes tumor growth. While no specific clinical trials directly evaluate this exact combination, comparative analyses of their monotherapy data from trials like KRYSTAL-1 (adagrasib), CodeBreaK100/200 (sotorasib) show comparable efficacy with adagrasib trending toward slightly better progression-free survival (PFS), though overall survival (OS) is similar; their combination is hypothesized to enhance efficacy or overcome resistance based on broader KRAS inhibitor strategies, but lacks dedicated evidence and may increase overlapping toxicities like gastrointestinal issues and hepatotoxicity.