EMA Validates Bristol Myers Squibb's Opdivo and Yervoy Application for Advanced Liver Cancer

Bristol Myers Squibb has announced that the European Medicines Agency (EMA) has validated its Type II variation application for the combination of Opdivo (nivolumab) and Yervoy (ipilimumab) as a first-line treatment for adult patients with unresectable or advanced hepatocellular carcinoma (HCC) who have not received prior systemic therapy. This validation signifies that the submission is complete and initiates the EMA’s centralized review process.

Hepatocellular carcinoma is the most prevalent form of liver cancer, accounting for 75% to 85% of all liver cancer cases. In the European Union, approximately 62,000 new liver cancer cases are diagnosed annually, a significant number of which are HCC. Despite recent advancements in treatment, patients diagnosed at more advanced stages often face poor prognoses, necessitating the development of therapies that offer better clinical outcomes.

The Type II variation application is supported by data from the Phase 3 CheckMate -9DW trial. This trial demonstrated that the combination of Opdivo and Yervoy significantly improved overall survival compared to the standard treatment options, lenvatinib or sorafenib. The combination therapy also had a manageable safety profile consistent with previous data, with no new safety issues emerging. The results of this trial were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

Dana Walker, M.D., M.S.C.E., Vice President and Global Program Lead for gastrointestinal and genitourinary cancers at Bristol Myers Squibb, emphasized the importance of this development. "With such a high incidence of liver cancer in the European Union and the challenging prognosis for patients with advanced HCC, there is a significant need for new therapies that can improve clinical outcomes. We are eager to work with the EMA to bring this dual immunotherapy combination to patients."

The CheckMate -9DW trial is a Phase 3 randomized, open-label study that compared Opdivo plus Yervoy to lenvatinib or sorafenib monotherapy in patients with unresectable or advanced hepatocellular carcinoma who had not previously received systemic therapy. The trial included approximately 668 patients who were randomized to receive either the combination therapy or one of the monotherapies. The primary endpoint was overall survival, with key secondary endpoints including objective response rate and time to symptom deterioration.

Hepatocellular carcinoma is a significant global health concern and the third leading cause of cancer mortality worldwide. The disease is frequently diagnosed at an advanced stage, limiting treatment options and often resulting in poor outcomes. Recurrence is common, with up to 70% of patients experiencing a return of the disease within five years, especially those at high risk after surgery or ablation. The primary causes of HCC include hepatitis B and C infections, but other factors like metabolic syndrome and nonalcoholic steatohepatitis (NASH) are becoming increasingly significant contributors to the disease.

The validation of this application by the EMA could be a significant step forward in providing advanced HCC patients with a new, effective treatment option. The combination of Opdivo and Yervoy leverages the body’s immune system to combat cancer, offering a novel approach to treating this challenging disease. Bristol Myers Squibb continues to emphasize its commitment to cancer research, aiming to improve patient outcomes and quality of life through innovative therapies.

This announcement reflects Bristol Myers Squibb’s ongoing efforts to develop new treatment options for various cancers, using its expertise in Immuno-Oncology to explore the potential of immune checkpoint inhibitors like Opdivo and Yervoy. The company remains dedicated to transforming the lives of cancer patients around the world through scientific innovation and collaboration.