FDA Approves Nivolumab With Ipilimumab for Unresectable or Metastatic MSI-H or dMMR Colorectal Cancer

Nivolumab (Opdivo; Bristol Myers Squibb) with ipilimumab (Yervoy; Bristol Myers Squibb) is now FDA approved for patients aged ≥12 years with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair–deficient (dMMR) colorectal cancer (CRC). The FDA also converted the accelerated approval to regular approval for single-agent nivolumab for adult and pediatric patients aged ≥12 years with MSI-H or dMMR metastatic CRC that has progressed following fluoropyrimidine, oxaliplatin, and irinotecan.¹

Efficacy of nivolumab with ipilimumab was evaluated in CheckMate 9DW (NCT04008030), a 3-arm, open-label trial in immunotherapy-naïve patients with unresectable or metastatic CRC with known MSI-H or dMMR status. Patients were randomly assigned to receive 1 of the following treatments:

• Nivolumab 240 mg every 3 weeks and ipilimumab 1 mg/kg every 3 weeks for a maximum of 4 doses, then nivolumab 480 mg every 4 weeks
• Nivolumab 240 mg every 2 weeks for 6 doses, then nivolumab 480 mg every 4 weeks, or
• Investigator’s choice chemotherapy

The analysis of nivolumab plus ipilimumab versus chemotherapy in the first-line setting was conducted in 255 patients with centrally confirmed MSI-H/dMMR status of 303 patients based on local testing. Median progression-free survival (PFS) was not reached (NR) (95% confidence interval [CI], 38.4-not estimable [NE]) in the nivolumab plus ipilimumab arm and 5.8 months (95% CI, 4.4-7.8) in the chemotherapy arm (hazard ratio [HR], 0.21 [95% CI, 0.14-0.32]; P<.0001). Comparative results of overall response rate (ORR) and overall survival (OS) between arms were not available at the time of the interim PFS analysis due to statistical testing strategy.

The analysis of nivolumab plus ipilimumab versus nivolumab (all lines) was conducted in 582 patients with centrally confirmed MSI-H/dMMR status of 707 patients based on local testing. Median PFS was NR (95% CI, 53.8-NE) in the nivolumab plus ipilimumab arm and 39.3 months (95% CI, 22.1-NE) in the nivolumab arm (HR, 0.62 [95% CI, 0.48-0.81]; P=.0003). ORR was 71% (95% CI, 65-76) in the nivolumab plus ipilimumab arm and 58% (95% CI, 52-63) in the nivolumab arm (P=.0011). The comparative results of OS between arms were not available at the interim PFS analysis due to statistical testing strategy.

Reference

1. FDA. FDA approves nivolumab with ipilimumab for unresectable or metastatic MSI-H or dMMR colorectal cancer [press release]. April 8, 2025. Accessed April 30, 2025. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-nivolumab-ipilimumab-unresectable-or-metastatic-msi-h-or-dmmr-colorectal-cancer