Promising single-agent activity from AMG510 (sotorasib) and MRTX849 (adagrasib) in KRASG12C-mutant tumors, especially in non–small-cell lung cancer (NSCLC) and colorectal cancer (CRC), has provided the first clinical evidence of KRAS-mutant tumor inhibition7-9 and led to the subsequent US Food and Drug Administration breakthrough therapy designation for sotorasib in locally advanced or metastatic NSCLC. The gene discussed is KRAS; the disease is non-small cell lung carcinoma.