Sotorasib Plus Panitumumab Approved for Patients With KRAS G12C-Mutated Colorectal Cancer

On January 16, 2025, the US Food and Drug Administration (FDA) approved sotorasib plus panitumumab for adult patients with KRAS G12C-mutated metastatic colorectal cancer, as determined by an FDA-approved test. The FDA additionally approved the therascreen KRAS RGQ PCR kit as a companion diagnostic tool to identify patients eligible for this regimen. 

This approval was based on results from the phase 3 CodeBreaK 300 trial. In this open-label study, 160 patients who previously received fluoropyrimidine plus oxaliplatin and irinotecan-based chemotherapy were enrolled. Patients were randomized on a 1-to-1-to-1 basis to receive either 960 mg or 240 mg of oral sotorasib plus 6 mg/kg of intravenous panitumumab every 2 weeks, or investigator’s choice standard of care (trifluridine plus tipiracil or regorafenib). The primary end point was progression-free survival (PFS), by blinded independent central review. Key secondary end points included overall response rate (ORR), duration of response, and safety. 

At analysis, the median PFS was 5.6 months in the 960 mg sotorasib arm and 2 months in the standard of care arm (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.3 to 0.78; P = .005). The final analysis of PFS for patients in the 240 mg sotorasib arm compared to the standard of care arm was not statistically significant. The ORR was 26% in the 960 mg sotorasib arm and 0% in the standard of care arm. The median duration of response was 4.4 months in the 960 mg sotorasib arm. 

The most common adverse reactions occurring in ≥ 20% of patients included rash, dry skin, diarrhea, stomatitis, fatigue, and musculoskeletal pain. The most common grade 3/4 laboratory abnormalities occurring in ≥ 2 patients included decreased magnesium, decreased potassium, decreased corrected calcium, and increased potassium. 

The recommended dose of oral sotorasib is 960 mg once daily and the recommended dose of intravenous panitumumab is 6 mg/kg every 14 days, administered until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued. The first dose of sotorasib should be administered before the first dose of panitumumab. 

Source: 

FDA approves sotorasib with panitumumab for KRAS G12C-mutated colorectal cancer. Accessed on January 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sotorasib-panitumumab-kras-g12c-mutated-colorectal-cancer