Phase 1b trial of sotorasib plus panitumumab for chemotherapy-refractory metastatic colorectal cancer with KRAS-G12C mutation

The current third- and later-line treatment options for RAS-mutant metastatic colorectal cancer have limited efficacy. A phase 1b substudy of the CodeBreaK 101 protocol evaluated that combination of sotorasib (KRAS-G12C inhibitor) and panitumumab (EGFR inhibitor) for chemotherapy-refractory metastatic colorectal cancer with KRAS-G12C mutation. The primary endpoints were safety and tolerability. Treatment-related adverse events of any grade and grade ≥ 3 occurred in 94% and 27% of patients, respectively. Confirmed objective response rate was 30.0% (95% CI 16.6-46.5). Median progression-free survival was 5.7 months (95% CI 4.2-7.7) and median overall survival was 15.2 months (12.5-NE). The authors conclude that among patients with chemotherapy-refractory metastatic KRAS G12C mutated colorectal cancer, the combination of sotorasib and panitumumab had acceptable safety and promising activity.