THE U.S. Food and Drug Administration (FDA) approved a novel combination therapy for adults with KRAS G12C-mutated metastatic colorectal cancer (mCRC). This approval, based on results from the CodeBreaK 300 clinical trial, offers a new treatment option for patients who have progressed after prior chemotherapy regimens involving fluoropyrimidine, oxaliplatin, and irinotecan.
The study evaluated 160 patients randomized into three groups: two arms combining sotorasib with panitumumab at different doses, and one standard-of-care (SOC) group receiving either trifluridine/tipiracil or regorafenib. Patients receiving sotorasib 960 mg daily with panitumumab 6 mg/kg every two weeks demonstrated a median progression-free survival (PFS) of 5.6 months compared to 2 months in the SOC group (HR 0.48; p=0.005). The overall response rate (ORR) was 26% for the treatment arm versus 0% in the SOC group, and the median duration of response (DOR) was 4.4 months.
Common side effects for the approved regimen included rash, dry skin, diarrhea, fatigue, and musculoskeletal pain. The most frequently observed Grade 3-4 lab abnormalities included reduced magnesium and potassium levels. The recommended dosing is 960 mg of sotorasib orally once daily and 6 mg/kg of panitumumab via IV infusion every two weeks.
This regulatory decision was facilitated by the Real-Time Oncology Review (RTOR) pilot program, enabling the FDA to streamline its assessment. This approval marks a significant step forward for patients with KRAS G12C-mutated mCRC, providing an additional treatment pathway for a historically challenging condition.
Reference: U.S. Food 7 Drug Administration. FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer. Last accessed: January 17, 2025.
Anaya Malik | AMJ
