FDA Accepts Bristol Myers Squibb's Application for Opdivo and Yervoy in Advanced Colorectal Cancer

Bristol Myers Squibb has announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental biologics license application for the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a first-line treatment option for adults and children aged 12 and older with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) colorectal cancer (mCRC). This development follows the FDA granting the application Breakthrough Therapy Designation and Priority Review status, aiming for a Prescription Drug User Fee Act goal date of June 23, 2025.

The decision to accept the application is rooted in the outcomes of the Phase 3 CheckMate -8HW clinical trial. In this study, the combination of Opdivo and Yervoy showed superior progression-free survival compared to Opdivo alone and standard chemotherapy chosen by investigators. The results, verified by a Blinded Independent Central Review, were initially shared at the 2024 American Society of Clinical Oncology Gastrointestinal Cancers Symposium, with updated findings presented in 2025. The safety profile for the dual immunotherapy was consistent with prior data, with no new safety signals detected. The trial continues to evaluate secondary endpoints, such as overall survival.

Opdivo and Yervoy had previously received approval in July 2018 for treating MSI-H or dMMR mCRC that has progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan. Additionally, in December 2024, the combination was approved by the European Union for first-line treatment of adult patients with MSI-H or dMMR unresectable or metastatic colorectal cancer, with a similar approval in China by the National Medical Products Administration in October 2024.

The CheckMate -8HW trial involved 839 participants randomized into three groups: one receiving Opdivo alone, another receiving the combination of Opdivo and Yervoy, and the third receiving chemotherapy chosen by investigators. The trial’s primary focus was on progression-free survival for the combination therapy compared to chemotherapy in the first-line setting, and versus Opdivo alone across all treatment lines.

Colorectal cancer is a significant global health issue, being the third most diagnosed cancer worldwide and the second leading cause of cancer-related deaths. For patients with dMMR or MSI-H tumors, traditional chemotherapy is often less effective, resulting in a more challenging prognosis. The novel combination of Opdivo and Yervoy offers a potential new treatment avenue for these patients.

Opdivo operates as a PD-1 immune checkpoint inhibitor, aiming to enhance the body's immune response against tumors. Since its first global approval in July 2014, Opdivo has been approved in over 65 countries for various cancer treatments. The combination with Yervoy, which functions by targeting CTLA-4 to augment T-cell activity, has been a significant advancement in immuno-oncology, initially approved for metastatic melanoma treatment.

Bristol Myers Squibb continues to pursue innovative cancer therapies, driven by a commitment to improve patient outcomes and advance cancer treatment standards globally. Their collaboration with Ono Pharmaceutical has expanded the reach of their immunotherapy solutions, excluding territories like Japan, South Korea, and Taiwan, where Ono maintains rights. This collaboration has been pivotal in advancing the global development and commercialization of these groundbreaking treatments.