RMC-9805 + cetuximab

RMC-9805 + cetuximab is an investigational combination therapy comprising **RMC-9805**, a small molecule, orally bioavailable, covalent, G12D-selective RAS(ON) inhibitor, and **cetuximab**, an anti-EGFR monoclonal antibody. **RMC-9805** targets the oncogenic KRAS G12D mutation by forming a non-covalent ligand-mediated complex with cyclophilin A and GTP-bound RAS, leading to covalent modification of mutant Asp12 and selective inhibition of downstream RAS signaling. This results in impaired cell proliferation and apoptosis in KRAS G12D mutant tumors[1][2][6][7][8][10]. **Cetuximab** is a chimeric monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), inhibiting EGFR-mediated signal transduction and tumor cell growth. The combination leverages these complementary mechanisms, aiming to enhance anti-tumor responses in KRAS G12D-mutant solid tumors. RMC-9805 is developed by Revolution Medicines and is currently in Phase 1 clinical evaluation as monotherapy, but no public clinical trial data currently confirm combination use with cetuximab specifically[1][2][3][7].