LY3499446 + cetuximab

**LY3499446 + cetuximab** is a combination regimen under clinical investigation for the treatment of advanced solid tumors, particularly those harboring **KRAS G12C mutations** such as colorectal cancer (CRC). **LY3499446** is an orally available small molecule inhibitor designed to covalently and selectively bind to the KRAS G12C mutant protein, thereby inhibiting mutant KRAS-driven signaling pathways critical for tumor cell growth and survival. **Cetuximab** is an intravenously administered chimeric monoclonal antibody targeting the epidermal growth factor receptor (**EGFR**), blocking ligand binding, receptor activation, and downstream pro-tumorigenic signaling. The rationale for this combination is to simultaneously disrupt KRAS G12C mutant signaling and upstream EGFR-driven pathways, which can contribute to resistance mechanisms in colorectal cancer. This combination was evaluated in a multicenter, Phase 1/2 study sponsored by Eli Lilly in patients with KRAS G12C-mutant advanced solid tumors, with specific cohorts in colorectal cancer.