Dr Morris on the FDA Approval of Nivolumab/Ipilimumab for dMMR/MSI-H Metastatic CRC

“The recent update from the CheckMate 8HW trial that was reported at the [2025 Gastrointestinal Cancers Symposium was] important because it offers a new …FDA-approved treatment option for patients with MSI-H or dMMR metastatic CRC who have not received any prior treatment.”

Van Karlyle Morris, MD, an associate professor in the Department of Gastrointestinal (GI) Medical Oncology in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the significance of the FDA approval of nivolumab (Opdivo) plus ipilimumab (Yervoy) for the treatment of adult and pediatric patients at least 12 years of age with mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) unresectable or metastatic colorectal cancer (CRC).

On April 8, 2025, the FDA approved the combination of nivolumab and ipilimumab for this indication based on findings from the phase 3 CheckMate 8HW trial (NCT04008030). This regulatory decision represents a significant advancement for patients with CRC, including those with previously untreated disease, Morris said.

Previous data readouts from this 3-arm trial demonstrated that treatment with a combination of the PD-1 inhibitor nivolumab and the CTLA-4 inhibitor ipilimumab (n = 354) generated superior benefit compared with standard chemotherapy (n = 132) in patients with treatment-naive disease. However, until the most recent data update, no head-to-head findings existed to support the efficacy of dual checkpoint inhibition with nivolumab plus ipilimumab vs single-agent nivolumab (n = 353) across all lines of therapy, according to Morris.

Updated findings presented at the 2025 Gastrointestinal Cancers Symposium showed that among, patients with centrally confirmed MSI-H/dMMR disease, the median progression-free survival was not yet reached (95% CI, 53.8 months-not evaluable [NE]) with the combination vs 39.3 months (95% CI, 22.1-NE) with nivolumab monotherapy (HR, 0.62; 95% CI, 0.48-0.81; P = .0003). Additionally, the respective objective response rates in this population were 71% (95% CI, 65%-76%) vs 58% (95% CI, 52%-63%; P = .0011).