In a large unbiased clinicogenomic analysis of 424 patients with NSCLC, co-alterations of KEAP1, SMARCA4, and CDKN2A were correlated with poor clinical outcomes in patients with KRAS G12C-mutated NSCLC treated either with sotorasib or adagrasib. Here, CDKN2A is linked to non-small cell lung carcinoma.