FDA Approves Nivolumab Plus Ipilimumab for Unresectable/Metastatic Microsatellite Instability-High or Mismatch Repair Deficient Colorectal Cancer

On April 8th, 2025, the US Food and Drug Administration (FDA) approved nivolumab plus ipilimumab for patients 12 years of age and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). This approval was based on results from the CHECKMATE-8HW trial. 

In this open-label study, researchers randomized immunotherapy-naive patients to receive 240 mg of nivolumab plus 1 mg/kg of ipilimumab every 3 weeks for a maximum of 4 doses followed by 480 mg of nivolumab every 4 weeks, 240 mg of nivolumab every 2 weeks for 6 doses followed by 480 mg of nivolumab once every 4 weeks, or investigator’s choice chemotherapy. The primary end point was progression-free survival (PFS), as assessed by blinded independent central review. Key secondary end points included objective response rate (ORR), overall survival (OS), and safety. 

Among patients treated in the first-line setting (n = 255), median PFS was not reached in the nivolumab plus ipilimumab arm and 5.8 months in the chemotherapy am (hazard ratio [HR] 0.21; 95% confidence interval [CI], 0.14 to 0.32; P < .0001). Comparative results of ORR and OS were not available at the time of interim PFS analysis. Among patients treated in all lines (n = 582), median PFS was not reached in the nivolumab plus ipilimumab arm and 39.3 months in the nivolumab arm (HR 0.62; 95% CI, 0.48 to 0.81; P < .0003). The ORR was 71% and 58% (P < .0011), respectively. Comparative results of OS were not available at the time of interim PFS analysis. 

The most common adverse events reported in ≥ 20% of patients treated with nivolumab plus ipilimumab included fatigue, diarrhea, pruritus, abdominal pain, musculoskeletal pain, and nausea. The most common adverse events reported in ≥ 20% of patients treated with single agent nivolumab included fatigue, diarrhea, abdominal pain, pruritus, and musculoskeletal pain. 

The FDA has also approved single agent nivolumab for patients who experience disease progression after fluoropyrimidine, oxaliplatin, and irinotecan.

Source:  

FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer. Accessed on April 8, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-msi-h-or-dmmr-colorectal-cancer