JDQ443 + cetuximab

JDQ443 + cetuximab is a combination of two drugs: JDQ443, a structurally unique small molecule covalent inhibitor that selectively and irreversibly targets the GDP-bound form of KRAS G12C, and cetuximab, a recombinant monoclonal antibody that targets the epidermal growth factor receptor (EGFR). JDQ443 inhibits KRAS G12C-driven cellular signaling and proliferation by covalently binding to the mutant KRAS G12C protein, thereby blocking downstream MAPK signaling. Cetuximab binds EGFR on tumor cells, preventing ligand-induced receptor activation and signaling, reducing cell proliferation and survival. The combination is being investigated to overcome mechanisms of resistance to KRAS G12C inhibitors in solid tumors, notably non-small cell lung cancer (NSCLC) and colorectal cancer, as EGFR reactivation is a known resistance pathway to KRAS G12C inhibition.