Bristol Myers Squibb (NYSE: BMY) announced results of an analysis from the three-arm Phase 3 CheckMate -8HW trial evaluating Opdivo^® (nivolumab) plus Yervoy^® (ipilimumab) versus Opdivo monotherapy across all lines of therapy, including first-line, for the treatment of microsatellite instability-high/mismatch repair-deficient (MSI-H/dMMR) metastatic colorectal cancer (mCRC). At a median follow-up of 47 months, Opdivo plus Yervoy demonstrated a statistically significant and clinically meaningful improvement in the dual-primary endpoint of progression-free survival (PFS) as assessed by Blinded Independent Central Review (BICR) versus Opdivo monotherapy (HR 0.62; 95% CI 0.48–0.81; P = 0.0003).

These results will be featured in a late-breaking oral presentation (LBA143) at the American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium on January 25 at 1:00 p.m. Pacific Time, in San Francisco, California and published the same day in The Lancet .

Previous results from CheckMate -8HW, evaluating Opdivo plus Yervoy versus investigator’s choice of chemotherapy, demonstrated that Opdivo plus Yervoy reduced the risk of disease progression or death by 79%. The results were published in The New England Journal of Medicine and were the basis for a European Commission approval for first-line patients with MSI-H/dMMR mCRC in December 2024.

“The benefit of dual inhibition of PD-1 and CTLA-4 has been well established in Phase 3 trials of Opdivo plus Yervoy across a broad range of tumor types, including in MSI-H/dMMR mCRC compared to chemotherapy,” said Dana Walker, M.D., M.S.C.E., vice president, global program lead, late development, oncology, Bristol Myers Squibb. “The results from this analysis of the CheckMate -8HW trial answer affirmatively an important question about whether dual I/O therapy with Opdivo plus Yervoy can also improve outcomes for patients with MSI-H/dMMR mCRC compared with Opdivo alone.”

Results from the CheckMate -8HW trial at a median follow-up of 47 months in patients with MSI-H/dMMR mCRC across all lines of therapy include:

• PFS (progression-free survival; dual primary endpoint):OpdivoplusYervoydemonstrated a 38% reduction in the risk of disease progression or death versusOpdivo monotherapy [HR 0.62; 95% CI 0.48–0.81; P = 0.0003]. PFS rates at 12-, 24-, and 36-months were also higher compared toOpdivomonotherapy (76%, 71% and 68% versus 63%, 56% and 51%, respectively).
• ORR (overall response rate; secondary endpoint):ORR by BICR was significantly higher withOpdivoplusYervoycompared toOpdivomonotherapy [71% vs 58%; P = 0.0011].
• Safety:The safety profile for the combination ofOpdivoplusYervoyremained consistent with previously reported data and was manageable with established protocols. Grade 3/4 TRAEs were reported in 22% of patients withOpdivoplusYervoyand 14% of patients withOpdivo.No new safety signals were identified.

“The data presented today confirm nivolumab plus ipilimumab as a new standard treatment for people living with metastatic colorectal cancer given the evidence observed in both disease-free survival and response rate,” said Thierry Andre, M.D., Head of the Medical Oncology Department, Sorbonne University and Hospital Saint-Antoine, Paris, France. “Importantly, no new safety signals were identified, with a moderate increase of treatment-related adverse events, mostly grade 1 or 2, observed with the combination. Together, these data reaffirm the benefit of dual immunotherapy with nivolumab plus ipilimumab for this population of patients who urgently need improved treatment options.”

The study is ongoing to assess secondary endpoints, including overall survival (OS). Bristol Myers Squibb thanks the patients and investigators involved in the CheckMate -8HW clinical trial.