Frontline Combination Strategies in KRAS G12C-Mutant NSCLC

Faculty discuss the evolving frontline treatment landscape for KRAS G12C-mutant NSCLC, noting the limited outcomes achieved with current standard chemoimmunotherapy approaches. The panel reviews data on a next-generation KRAS G12C inhibitor studied in combination with immunotherapy, with or without chemotherapy, across a range of PD-L1 expression levels, including response rates and duration of response observed in early-phase and safety cohort data. Discussion addresses how these agents may benefit patients regardless of PD-L1 status and considers the broader class of KRAS G12C inhibitors in development. Faculty examine the observation that adding chemotherapy has not consistently improved response rates, explore hepatic toxicity and its clinical management, and discuss the biological rationale and evidence for potential synergy between KRAS G12C inhibition and immunotherapy.