Bristol Myers Squibb Builds First-Line Case for Opdivo-Yervoy Combo in Metastatic Colorectal Cancer (mCRC) with Phase III Data

PRINCETON, N.J. – Bristol Myers Squibb on Saturday released results from the Phase III CheckMate -8HW study showing that the combination of its PD-1 inhibitor Opdivo (nivolumab) and its CTLA-4 blocker Yervoy (ipilimumab) improved progression-free survival in certain metastatic colorectal cancer patients when used in the first-line setting.

Patients treated with the dual immunotherapy regimen saw a 79% drop in the risk of disease progression or death compared with chemotherapy. This effect was “statistically significant and clinically meaningful,” with a p-value less than 0.0001, according to BMS’s announcement.

At the time of the analysis, patients in the Opdivo plus Yervoy arm had not yet reached median progression-free survival (PFS), while chemotherapy counterparts saw a median PFS of 5.9 months. The PFS benefits associated with BMS’s combo regimen were apparent as early as three months and persisted throughout the duration of the study.

BMS presented these late-breaking data at an oral session during the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, held Jan. 18-20 in San Francisco.

Dana Walker, vice president and global program lead of gastrointestinal and genitourinary cancers at BMS, in a statement called these findings “unprecedented” while Thierry Andre, head of the Medical Oncology Department at Sorbonne University in Paris, said that these data could have “practice-changing potential.”

CheckMate-8HW is a randomized and open-label trial enrolling approximately 830 patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer. Patients in the control arm received the investigator’s choice of chemotherapy.

In addition to efficacy, CheckMate-8HW also assessed the safety of the combo regimen and found that its adverse events were consistent with what had been previously documented—and were manageable with established protocols. Treatment-related adverse events were more common in the chemotherapy arm.

CheckMate-8HW is ongoing and will continue to evaluate its second primary endpoint of PFS in patients receiving the immunotherapy combo versus Opdivo alone.

Saturday’s readout could position BMS to challenge Merck’s dominant PD-1 blocker Keytruda (pembrolizumab), which in June 2020 won the FDA’s approval as a first-line treatment option for MSI-H/dMMR metastatic colorectal cancer. This regulatory win was backed by data from the KEYNOTE-177 trial, which put Keytruda’s risk reduction at 40% for disease progression and death.

BMS’s PD-1/CTLA-4 combo could come out on top with a 79% risk reduction. Still, without direct head-to-head trials, it remains impossible to reliably compare Keytruda with the Opdivo/Yervoy regimen, particularly given differences in patient characteristics between the two trials.