First-line Immunotherapy Combination Approved for Colorectal Cancers Characterized by Genomic Instability
The FDA has approved nivolumab with ipilimumab in certain patients with advanced colorectal cancer.
The U.S. Food and Drug Administration (FDA) has approved nivolumab (Opdivo) with ipilimumab (Yervoy) for the treatment of patients 12 years and older with unresectable or metastatic colorectal cancer characterized by mismatch repair-deficient or microsatellite instability-high (dMMR/MSI-H) status. Additionally, an accelerated approval covering nivolumab monotherapy for certain patients with previously treated dMMR/MSI-H colorectal cancer was converted to full approval.
Nivolumab and ipilimumab are immunotherapies called immune checkpoint inhibitors, and by blocking the PD-1 and CTLA-4 pathways, respectively, they can improve the immune system’s ability to recognize and destroy cancer cells.
The approval of the nivolumab and ipilimumab combination was based on results from the open-label, randomized phase III CHECKMATE-8HW trial. In this three-arm study, 839 patients with unresectable or metastatic dMMR/MSI-H colorectal cancer were randomly assigned to receive nivolumab and ipilimumab together, nivolumab alone, or investigator’s choice of chemotherapy.
Among the 255 patients who received treatment in the first-line setting, the immune checkpoint inhibitor combination reduced the risk of disease progression or death by 79% compared with chemotherapy alone—half of chemotherapy-treated cancers had progressed at 5.8 months, whereas the median time to progression was not reached in the immunotherapy arm.
Among 582 patients who received treatment as part of any treatment line, the combination of nivolumab and ipilimumab reduced the risk of disease progression or death by 38% compared with nivolumab alone—half of nivolumab-treated cancers had progressed at 39.3 months, whereas the median time to progression was not reached in the combination arm. The response rate was significantly higher in the combination arm (71%) compared with the nivolumab arm (58%).
For patients who weigh at least 40 kg, the recommended dose is 240 mg nivolumab and 1 mg/kg ipilimumab on the same day every three weeks for a maximum of four cycles, followed by 240 mg nivolumab monotherapy every two weeks or 480 mg nivolumab monotherapy every four weeks.
For patients who weigh less than 40 kg, the recommended dose is 3 mg/kg nivolumab and 1 mg/kg ipilimumab on the same day every three weeks for a maximum of four cycles, followed by 3 mg/kg nivolumab monotherapy every two weeks or 6 mg/kg nivolumab monotherapy every four weeks.
Nivolumab can be given for up to two years or until disease progression or unacceptable toxicity.
Colorectal cancer is cancer that forms in the large intestine or rectum, and roughly 15% of colorectal cancer cases are characterized by dMMR. According to federal statistics, it was estimated that 154,270 individuals would be diagnosed with colorectal cancer and 52,900 patients would die of the disease in the United States in 2025.
The FDA rendered its decision on April 8, 2025. Check this resource for updated information on all therapeutics regulated by the FDA.