According to results from the phase 1b CodeBreaK 101 study, sotorasib plus panitumumab and FOLFIRI demonstrated long-term efficacy and safety among patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC). 

These data were first presented by John Strickler, MD, Duke University Medical Center, Durham, North Carolina, at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois. 

In this study, researchers enrolled 40 KRAS G12C inhibitor-naive patients who received ≥ 1 prior line of systemic treatment to receive 960 mg of daily sotorasib plus 6 mg/kg of panitumumab and standard FOLFIRI once every 2 weeks. The primary end point was safety. Key secondary end points included objective response rate (ORR), disease control rate, progression-free survival (PFS), and overall survival (OS). 

At analysis, the most common treatment-related adverse events included dermatitis acneiform and dry skin (n = 27), decreased neutrophil count (n = 20), and stomatitis (n = 17).  Grade ≥3 treatment-related adverse events occurred in 50% of patients. Adverse events led 2 patients to discontinue sotorasib and panitumumab and 1 patient to discontinue FOLFIRI. Updated ORR was 57.5% and the disease control rate was 92.5%. Median PFS was 8.2 months, and median OS was 17.9 months. 

“Sotorasib plus panitumumab and FOLFIRI showed promising long-term safety and efficacy in pretreated KRAS G12C-mutated mCRC,” concluded Dr Strickler et al. “The ongoing phase 3 study, CodeBreaK 301 aims to evaluate this combination against standard of care in first-line patients with KRAS G12C-mutated mCRC.” 

Source: 

Strictler J, Kuboki Y, Hong D, et al. Long-term safety and efficacy of sotorasib plus panitumumab and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreaK 101 (phase 1b). Presented at 2025 ASCO Annual Meeting. May 30-June 3, 2025; Chicago, IL. Abstract 3506