IBI351 + sintilimab

**IBI351 + sintilimab** is a combination therapy involving two agents: IBI351, an orally available selective, covalent and irreversible small molecule inhibitor targeting KRAS G12C, and sintilimab, a monoclonal antibody that inhibits the programmed cell death protein 1 (PD-1). IBI351 covalently binds to the cysteine 12 residue of the KRAS G12C mutant, thereby locking KRAS in its inactive GDP-bound state, and inhibiting downstream oncogenic signaling pathways. Sintilimab, an immune checkpoint inhibitor, binds to PD-1 on T cells, blocking its interaction with PD-L1 and PD-L2 and restoring anti-tumor immune responses. The combination therapy is currently under investigation for advanced or metastatic non-small cell lung cancer (NSCLC) with KRAS G12C mutations and may also be explored in other solid tumors with the same mutation. Development of this combination has focused on improving efficacy in first-line and refractory advanced NSCLC populations[1][3][4].