FDA Approves Opdivo Plus Yervoy Regimen for MSI-H/dMMR Colorectal Cancer

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The FDA has approved Bristol Myers Squibb’s (BMS) dual immunotherapy regimen of Opdivo (nivolumab) plus Yervoy (ipilimumab) as a first-line treatment for adult and pediatric patients aged 12 years and older with previously untreated, unresectable, or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). The approval, granted ahead of the FDA’s target review date, is based on data from the Phase III CheckMate-8HW trial.¹

“There is an unmet need for additional treatment options such as a dual immunotherapy approach for patients with previously untreated MSI-H/dMMR unresectable or metastatic CRC, which is an aggressive form of cancer and can be particularly difficult to treat,” said CheckMate-8HW investigator Heinz-Josef Lenz, MD, deputy director for research programs, head, gastrointestinal cancers program, USC Norris Comprehensive Cancer Center, in a press release. “The meaningful outcomes in CheckMate-8HW underscore how initiating treatment with the dual immunotherapy combination of nivolumab plus ipilimumab may result in a notable survival benefit. This approval has the potential to redefine traditional approaches of care for patients with this form of CRC.”

The randomized, multicenter, open-label CheckMate-8HW trial enrolled 839 patients, who were randomly assigned to receive either Opdivo plus Yervoy, Opdivo monotherapy, or investigator’s choice of chemotherapy comprised of mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab. The dual primary endpoints were progression-free survival (PFS) for Opdivo plus Yervoy vs. Opdivo across all lines of therapy and vs. chemotherapy in the first-line setting, both assessed by Blinded Independent Central Review. A key secondary endpoint was overall survival.

Results found that the dual immunotherapy regimen reduced the risk of disease progression or death by 38% compared to Opdivo monotherapy (HR 0.62; 95% CI: 0.48–0.81; P=0.0003). Median PFS was not reached for the combination, while it was 39.3 months for monotherapy. The 12-, 24-, and 36-month PFS rates for the combination regimen were 76%, 71%, and 68%, respectively, compared to 63%, 56%, and 51% with monotherapy. The overall response rate was also higher with the combination at 71% vs. 58% for monotherapy (P=0.0011).

Compared to chemotherapy in the first-line setting, Opdivo plus Yervoy reduced the risk of progression or death by 79% (HR 0.21; 95% CI: 0.14–0.32; P<0.0001). Median PFS was not reached for the combination arm, while it was 5.8 months with chemotherapy. The 12- and 24-month PFS rates were 79% and 72% with the combination, compared to 21% and 14% for chemotherapy. Kaplan-Meier curves showed an early and sustained separation favoring the combination therapy in both comparisons.¹

“This approval marks our ninth indication for an Opdivo-based treatment in the gastrointestinal space,” said Wendy Short Bartie, SVP, oncology commercialization, BMS, in the press release.“We are witnessing the transformative potential of dual immunotherapy in treating GI cancers. People with MSI-H/dMMR metastatic colorectal cancer face high unmet need, and Opdivo plus Yervoy is an important new approach in the first-line setting. This milestone can offer hope, and it underscores our commitment to continue reaching more patients with new treatment options.”

Safety data for the combination regimen was consistent with previous findings. Serious adverse events (AEs) were reported in 46% of patients receiving the combination. The most common serious AEs included adrenal insufficiency; hypophysis; diarrhea; abdominal pain; small intestinal obstruction; pneumonia; acute kidney injury; immune mediated enterocolitis; pneumonitis; colitis; large intestinal obstruction; and urinary tract infection.¹

“Colorectal cancer is the third most commonly diagnosed cancer and the second most common cause of cancer-related death for men and women combined in the United States, and concerning trends show that incidence is increasing in people younger than 50,” said Nicole Sheahan, president, global colon cancer association, in the press release. “Despite the prevalence of CRC, there remains a high unmet need, highlighting the urgency for additional treatment options. We are thrilled with this FDA approval as Opdivo plus Yervoy offers an exciting new first-line approach for patients with MSI-H/dMMR metastatic colorectal cancer.”

Reference

1. U.S. Food and Drug Administration Approves Opdivo® (nivolumab) plus Yervoy® (ipilimumab) as a Treatment for Patients with Previously Untreated Microsatellite Instability-High or Mismatch Repair Deficient Unresectable or Metastatic Colorectal Cancer. BMS. April 8, 2025. Accessed April 9, 2025. https://news.bms.com/news/details/2025/U-S--Food-and-Drug-Administration-Approves-Opdivo-nivolumab-plus-Yervoy-ipilimumab-as-a-Treatment-for-Patients-with-Previously-Untreated-Microsatellite-Instability-High-or-Mismatch-Repair-Deficient-Unresectable-or-Metastatic-Colorectal-Cancer1/default.aspx