The US Food and Drug Administration (FDA) accepted Bristol-Myers Squibb Company's supplemental Biologics License Application (sBLA) for Opdivo (nivolumab) in combination with Yervoy (ipilimumab) for the treatment of adults with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC) that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

The FDA granted the application priority review and, in February 2018, granted the combination Breakthrough Therapy Designation for this potential indication, recognizing the need for new treatment approaches in this patient population. The FDA action date is July 10, 2018.

“The FDA acceptance of this application with priority review reinforces our belief in the potential of the Opdivo plus Yervoy combination to treat patients with previously treated metastatic colorectal cancer defined by MSI-H or dMMR biomarkers, and is a result of our longstanding commitment to the exploration of I-O/I-O combinations for patient populations with high unmet need,” said Ian M. Waxman, M.D., development lead, Gastrointestinal Cancers, Bristol-Myers Squibb. “We look forward to working with the FDA with the goal of bringing this combination to these colorectal cancer patients.”

This application is based on data from the ongoing phase 2 CheckMate -142 study evaluating the Opdivo and Yervoy combination in previously treated patients with MSI-H or dMMR mCRC. Data from this study were presented in January at the 2018 Gastrointestinal Cancers Symposium and published simultaneously in the Journal of Clinical Oncology.

The FDA’s Breakthrough Therapy Designation is a process intended to enable timely patient access by expediting the development and review of medicines for serious conditions where preliminary clinical evidence indicates a substantial improvement over available therapies on one or more clinically significant endpoints.

Colorectal cancer (CRC) is cancer that develops in the colon or the rectum, which are part of the body’s digestive or gastrointestinal system. In the US, CRC is the third most common cancer with more than 140,000 new cases expected to be diagnosed annually, and the third leading cause of cancer-related deaths among men and women combined.

DNA mismatch repair deficiency (dMMR) occurs when the proteins that repair mismatch errors in DNA replication are missing or non-functional, leading to microsatellite instability-high (MSI-H) tumors. Approximately 15% of CRC patients and 4-5% of metastatic CRC patients have MSI-H or dMMR biomarkers. Patients with MSI-H or dMMR metastatic CRC are less likely to benefit from conventional chemotherapy and typically have a poor prognosis. Routine testing to confirm MSI-H or dMMR status should be conducted for all CRC patients.

Opdivo is a programmed death-1 (PD-1) immune checkpoint inhibitor that is designed to uniquely harness the body’s own immune system to help restore anti-tumor immune response. By harnessing the body’s own immune system to fight cancer, Opdivo has become an important treatment option across multiple cancers.

Opdivo’s leading global development program is based on Bristol-Myers Squibb’s scientific expertise in the field of Immuno-Oncology and includes a broad range of clinical trials across all phases, including Phase 3, in a variety of tumor types. To date, the Opdivo clinical development program has enrolled more than 25,000 patients. The Opdivo trials have contributed to gaining a deeper understanding of the potential role of biomarkers in patient care, particularly regarding how patients may benefit from Opdivo across the continuum of PD-L1 expression.

In July 2014, Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world. Opdivo is currently approved in more than 60 countries, including the United States, the European Union and Japan. In October 2015, the Company’s Opdivo and Yervoy combination regimen was the first Immuno-Oncology combination to receive regulatory approval for the treatment of metastatic melanoma and is currently approved in more than 50 countries, including the United States and the European Union.