Bristol Myers Squibb announced that the U.S. Food and Drug Administration (FDA) approved Opdivo^® (nivolumab) plus Yervoy^® (ipilimumab) as a first-line treatment of adult and pediatric patients (12 years and older) with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (CRC). This approval is based on the CheckMate-8HW trial, which is the largest Phase 3 trial (n=839) of immunotherapy in patients with MSI-H/dMMR mCRC, evaluating Opdivo plus Yervoy (n=354) vs. Opdivo monotherapy (n=353) in the all-lines setting and Opdivo plus Yervoy (n=202) vs. investigator’s choice chemotherapy (n=101) (mFOLFOX-6 or FOLFIRI with or without bevacizumab or cetuximab) in the first-line setting.¹ Opdivo plus Yervoy met the dual primary endpoints of progression free survival (PFS) when compared to Opdivo monotherapy across all lines of therapy and when compared to chemotherapy in the first-line setting, as assessed by Blinded Independent Central Review (BICR). This approval, granted more than two months ahead of the June 23, 2025 Prescription Drug User Fee Act goal date, follows the FDA’s prior decision to grant the application Breakthrough Therapy Designation and Priority Review status.

“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 Heinz-Josef Lenz, MD, CheckMate-8HW investigator and Deputy Director for Research Programs and Head of the Gastrointestinal Cancers Program at the USC Norris Comprehensive Cancer Center. “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.”

In the CheckMate-8HW trial, Opdivo plus Yervoy demonstrated a 38% reduction in the risk of disease progression or death vs. Opdivo monotherapy in immunotherapy-naïve patients across all lines of therapy (Hazard Ratio [HR] 0.62; 95% Confidence Interval [CI] 0.48–0.81; P=0.0003). Assessing the dual primary endpoint of PFS, the trial demonstrated that median PFS was not reached with Opdivo plus Yervoy (95% CI: 53.8-Not Estimable [NE]) and was 39.3 months with Opdivo monotherapy (95% CI: 22.1-NE). PFS rates at 12-, 24-, and 36-months were also numerically higher compared to Opdivo monotherapy (76% vs. 63%, 71% vs. 56%, and 68% vs. 51%, respectively). In Kaplan-Meier (KM) curves showing PFS rates with Opdivo plus Yervoy compared to Opdivo monotherapy, an early separation was observed at two months and sustained at three years. Opdivo plus Yervoy also met a key secondary endpoint, demonstrating superior overall response rate (ORR) by BICR compared to Opdivo monotherapy (n=296, 71% vs. n=286, 58%; P=0.0011). Of the most common all-cause adverse reactions (ARs) occurring in ≥10% of patients, similar rates of grade 3-4 ARs were observed between Opdivo plus Yervoy and Opdivo monotherapy. The safety profile for the dual immunotherapy combination remained consistent with previously reported data and the ARs observed were manageable with established protocols, with no new safety signals identified. Additional safety information can be found in the U.S. Full Prescribing Information for Opdivo.