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IBI351 + cetuximab is a combination therapy investigated primarily for solid tumors harboring the KRAS G12C mutation, particularly in colorectal cancer and potentially other cancers. **IBI351 (fulzerasib, GFH925)** is an orally administered, selective, covalent, and irreversible inhibitor of KRAS G12C, designed to block the activation of the KRAS G12C pathway by modifying the mutant cysteine residue, thereby inhibiting downstream signaling that drives cancer cell proliferation and survival. **Cetuximab** is a chimeric monoclonal antibody directed against the epidermal growth factor receptor (EGFR), inhibiting receptor activation and downstream oncogenic signaling. This combination is being studied to overcome resistance mechanisms and enhance anti-tumor efficacy in KRAS G12C-mutant cancers. Preliminary phase 2 results in metastatic colorectal cancer show an objective response rate of 80% and a disease control rate of 100% among evaluable patients, including good activity in those with brain metastases.
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