John Strickler, MD, Duke Cancer Center, Durham, North Carolina, discusses results from the CodeBreaK 101 study which assessed FOLFIRI plus sotorasib and panitumumab among patients with KRAS G12C-mutated metastatic colorectal cancer (mCRC). Study results demonstrated that the addition of FOLFIRI demonstrated promising long-term efficacy and safety in this patient population. 

These data were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.  

Key Clinical Takeways

• Patient Population
  • KRAS G12C-mutated metastatic colorectal cancer (mCRC)
  • Previously treated, second-line or later setting
  • Cohort G: 40 patients in global phase 1B basket trial
• Treatment Regimen
  • Sotorasib 960 mg daily (KRAS G12C inhibitor)
  • Panitumumab (anti-EGFR antibody)
  • FOLFIRI (irinotecan-based chemotherapy backbone)
• Efficacy Outcomes
  • Response rate: 55% overall, including in patients pretreated with irinotecan
  • Progression-free survival (PFS): 8.2 months overall; consistent across lines (7-8 months)
  • Overall survival (OS): 15.6 months overall; slightly lower in heavily pretreated patients
• Safety Profile
  • No discontinuations of sotorasib due to treatment-related adverse events
  • Most dose modifications occurred with FOLFIRI; targeted agents well-tolerated
  • No unexpected safety signals; favorable safety profile overall
• Clinical Implications
  • Combination demonstrates robust activity and tolerability in refractory KRAS G12C-mutated mCRC
  • Supports further investigation of this triplet in first-line setting
  • Ongoing CodeBreaK 301 phase 3 trial evaluating front-line use

Transcript: 

Hi, I'm John Strickler, GI Medical Oncologist at Duke University Medical Center. It's my pleasure to talk about long-term safety and efficacy for sotorasib plus panitumumab and FOLFIRI for patients with previously treated KRAS G12C-mutated metastatic colorectal cancer. This is out of the CodeBreaK 101 study. 

Just as some background, sotorasib is a KRAS G12C inhibitor, panitumumab is an anti -EGFR therapy. It's been found already that the combination of sotorasib and panitumumab is highly active for patients with KRAS G12C-mutated metastatic colorectal cancer and in fact, this is an FDA-approved regimen. Additionally, some work previously has shown that cytotoxic chemotherapy pairs well with sotorasib and panitumumab and drives up response rate and durability of response and appears to be active in the first-line setting and other lines of therapy. 

At ASCO, I presented results of the phase 1B CodeBreaK 101 trial, exploring a cohort of patients with KRAS G12C-mutated metastatic colon cancer treated with the combination of sotorasib, panitumumab, and FOLFIRI in the second-line or later setting. Now this was a global, phase 1B cohort out of this basket trial. In total, 40 patients were treated in this dose-expansion cohort, which we called cohort G. All patients received FOLFIRI, panitumumab, and sotorasib, with sotorasib at 960 mg daily. In this study, 20 patients had progressed on prior irinotecan-based treatment, and yet even among these patients, the response rate was 55%. Also notably, progression free survival was high at 8.2 months in this overall study population, and we did note that progression-free survival remained high for patients, regardless of line-of-therapy, ranging between 7 to 8 months. Finally, overall survival was robust in this patient population. We did note that overall survival remained at 15.6 months overall, and it was slightly lower among patients who were more heavily pretreated. 

Finally, with respect to safety, we noted overall this was a very favorable regimen. No patients discontinued sotorasib due to a treatment-related adverse event, and typically we were seeing dose reductions or modifications of the FOLFIRI combo but very few patients needed to discontinue the targeted therapeutics in this regimen. 

Overall, this combination of sotorasib, panitumumab, and FOLFIRI showed very promising long-term safety and efficacy in patients with heavily refractory KRAS G12C-mutated metastatic colorectal cancer. There were no unexpected safety signals, overall generally well tolerated, so based on these results the plan is to look at the first-line combination of FOLFIRI, sotorasib, and panitumumab in the phase 3 CodeBreaK 301 study, and that study is ongoing. Thank you.

Source: 

Strickler 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