BMS-986466 + adagrasib + cetuximab

BMS-986466 + adagrasib + cetuximab is an investigational **three-drug combination regimen** studied in the treatment of cancers harboring the **KRAS G12C mutation**, with a major focus on advanced solid tumors and especially colorectal cancer. BMS-986466 (also called BBP-398 or IACS-15509) is an oral small molecule **SHP2 inhibitor**; adagrasib (also known as MRTX849) is an oral **KRAS G12C inhibitor** approved for non-small cell lung cancer; and cetuximab is a monoclonal antibody targeting the **epidermal growth factor receptor (EGFR)** used for colorectal and head & neck cancers. The combination is designed to overcome resistance mechanisms and improve efficacy by inhibiting parallel pathways in the RAS/MAPK signaling axis. Early clinical studies tested the safety and tolerability of this regimen in patients with KRAS G12C mutant tumors, particularly in colorectal cancer, but the studies ended early due to business decisions—not for safety reasons.