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Pembrolizumab + sotorasib is a combination therapy being investigated for the treatment of KRAS G12C-mutated non-small cell lung cancer (NSCLC). Sotorasib is a KRAS G12C inhibitor that received FDA accelerated approval in May 2021 for previously treated KRAS G12C-mutated advanced NSCLC. Pembrolizumab is a PD-1 inhibitor commonly used in immunotherapy regimens. The combination is being studied particularly for patients with PD-L1 negative expression, where standard immunotherapy-based treatments show poor 5-year progression-free survival rates (2-10%). Preclinical evidence suggests that PD-1 inhibition may synergize with sotorasib to enhance CD8-positive T-cell infiltration and inhibit tumor growth.
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