Sotorasib, Panitumumab, FOLFIRI for First-Line KRAS G12C-Mutated mCRC

The phase Ib CodeBreaK 101 study assessed the safety and efficacy of sotorasib (soto), panitumumab (pani), and FOLFIRI for first-line treatment of KRAS G12C-mutated metastatic colorectal cancer (mCRC).

Results for treatment-naïve patients are being presented by Dr. Salvatore Siena and colleagues at the European Society for Medical Oncology Congress 2024.

Initial results of CodeBreaK 101 showed that the addition of soto plus pani to FOLFIRI had an acceptable safety profile and a promising response rate of 60% for patients with previously treated KRAS G12C–mutated mCRC.

A total of 40 patients who had not received any prior systemic therapy for metastatic disease were enrolled at 17 global sites from July 2021 to March 2024. All patients received the recommended phase 2 dose of soto (960 mg oral once daily), pani (6 mg/kg IV once every 2 weeks), and FOLFIRI (IV once every 2 weeks).

The primary endpoint was safety and tolerability. Secondary endpoints included objective response rate, disease control rate, and median time to response.

Dr. Siena and colleagues reported that treatment-related adverse events (TRAEs) of any grade occurred in 100% of patients, and grade 3 or higher TRAEs occurred in 53% of patients. No deaths were reported.

Among the most common grade 3 or higher TRAEs were neutropenia (23%), dermatitis acneiform (18%), and diarrhea (10%).

In addition, researchers reported partial responses to treatment in 30 patients, with an overall response rate of 75%. The disease control rate was 93% and the median time to treatment response was 1.5 months.

“This study provides the first data set on the use of a KRAS^G12C inhibitor in first-line mCRC,” Dr. Siena and colleagues concluded. “The combination of soto, pani, and FOLFIRI demonstrated a tolerable safety profile and promising response rates in pts with treatment-naïve KRAS G12C–mutated mCRC.”

CodeBreaK 301, the subsequent phase 3 study, is currently enrolling to evaluate soto, pani, and FOLFIRI as a first-line option against the standard of care.