An international phase 3 clinical trial showed that patients with metastatic colorectal cancer who carry a rare genetic tumor mutation called KRAS G12C received a combination of the KRAS inhibitor sotorasib and the monoclonal antibody panitumumab compared to standard treatment. It was found that an excellent progression-free survival rate was achieved. City of Hope is a participating site, and City of Hope researchers are lead authors on this paper. New England Medical Journal Research published this week.
Standard chemotherapy often fails to control or eliminate disease in patients with the KRAS G12C mutation, leading to worse outcomes. Therefore, it is important to identify new treatment options after disease progression with first- and second-line chemotherapy, such as fluoropyrimidines, oxaliplatin, and irinotecan.
“This is the first phase 3 clinical trial to demonstrate benefit over standard treatment in patients with the KRAS G12C mutation whose cancer progressed after receiving standard chemotherapy. Efficacy of our study The results are promising in this unmet need population and should establish a new standard of care for patients with metastatic colorectal cancer with the KRAS G12C mutation who have progressed after previous standard therapy.” said Dr. Marwan Fakih. He is a Doctor of Clinical Oncology and Therapeutic Research and the Judy and Bernard Briskin Special Director of Clinical Research at City of Hope. Fakih is the lead author of the new study and principal investigator of the City of Hope clinical trial.
Based on positive results from a Phase 2 trial evaluating the combination of sotorasib, a KRAS G12C inhibitor, and panitumumab, an antibody that targets the epidermal growth factor receptor in normal and tumor cells, the The Phase 3 trial evaluated the same two drugs and tested sotorasib. Two different doses. All participants in the randomized trial were progressing on standard chemotherapy and received either 240 mg of sotorasib and panitumumab, 960 mg of sotorasib and panitumumab, or standard treatment with anticancer drugs (trifluridine and tipiracil). was administered. or regorafenib).
encouraging results
Both low and high doses of sotorasib in combination with panitumumab achieved better progression-free survival than other anticancer agents. The high-dose regimen was particularly effective, more than doubling the median time to progression compared to standard treatment, Dr. Fakih reported. Furthermore, with the high-dose regimen, far more patients showed major disease regression, and “the response rate was 26.4% instead of zero,” he added.
“Although this study sets a new standard following advances in standard chemotherapy, additional studies have shown “This raises questions about the value of this regimen in such cases,” Fakih said. “Additionally, ongoing biomarker studies will help better define the mechanisms of resistance to this target combination and how to overcome such challenges.”
The clinical trial, funded by Amgen, is ongoing but is not recruiting participants.
Top photo: Diagram of colorectal cancer cells.