A physician-scientist at City of Hope has identified a novel combination immunotherapy regimen—a triplet therapy consisting of regorafenib, ipilimumab, and nivolumab—that demonstrated significant response in patients with chemotherapy-resistant, microsatellite-stable metastatic colorectal cancer. The phase I data were presented by Marwan Fakih, MD, at the European Society for Medical Oncology (ESMO) Congress 2022 (Abstract 320M0).
The study enrolled 29 patients with chemotherapy-resistant, microsatellite-stable metastatic colorectal cancer. The participants received a combination immunotherapy treatment consisting of ipilimumab and nivolumab, plus the targeted therapy regorafenib. Of the 22 patients whose cancer had not yet spread to the liver, more than 50% are still alive after 20 months. The seven patients whose disease had spread to the liver also received the study treatment, but they had a less favorable outcome, with a median survival of 7 months.
Marwan Fakih, MD
“The combination immunotherapy regimen shows remarkable activity in [patients with] metastatic [microsatellite-stable disease] without liver metastases—a patient population previously regarded as nonresponsive to immunotherapeutic strategies,” said Dr. Fakih, Co-Director of City of Hope’s Gastrointestinal Cancer Program and primary investigator of the clinical trial. “To see a response rate of 40% and median overall survival exceeding 20 months in [patients with] refractory colorectal cancer without liver metastatic disease... is unprecedented.” Dr. Fakih is also Professor in the cancer center’s Department of Medical Oncology & Therapeutics Research and the Judy & Bernard Briskin Distinguished Director of Clinical Research.
In a previous study, Dr. Fakih had noted there was a modest benefit when treating patients with metastatic colorectal cancer without liver disease with nivolumab and regorafenib. Here, he showed that adding a CTLA-4 inhibitor, ipilimumab, appears to improve the health outcome in this subgroup of patients. (In a small sample of patients with liver metastases, the addition of CTLA-4 inhibitors did not appear to lead to major clinical benefits.)
“Our data confirms the importance of the tumor microenvironment in shaping the response to immunotherapy. Patients without liver metastatic disease can respond to a combination of checkpoint inhibitors, plus a small molecule VEGR tyrosine kinase inhibitor, as we have shown with our regimen,” Dr. Fakih said.
Dr. Fakih leading a team of researchers who are exploring further the role of anti–PD-1/CTLA-4 antibody combinations in microsatellite-stable colorectal cancer.
Disclosure: For full disclosures of the study authors, visit oncologypro.esmo.org.
