EU Approves Opdivo and Yervoy Combo for Advanced Liver Cancer

On March 7, 2025, Bristol Myers Squibb made a significant announcement regarding cancer treatment advancements. The European Commission (EC) has authorized the use of Opdivo® (nivolumab) combined with Yervoy® (ipilimumab) for front-line therapy in adult patients with unresectable or advanced hepatocellular carcinoma (HCC). This approval is rooted in the findings from Phase 3 CheckMate -9DW clinical trials, showcasing a noteworthy enhancement in overall survival when compared to other treatments such as lenvatinib or sorafenib.

Dana Walker, M.D., M.S.C.E., who is the vice president and Opdivo global program lead at Bristol Myers Squibb, emphasized the importance of this approval in enriching the pool of evidence supporting the efficacy of dual immunotherapy. She highlighted that this new treatment option could potentially extend the lives of patients battling hepatocellular carcinoma. Walker expressed excitement about introducing this first-line treatment to patients in the European Union.

The approval is supported by the CheckMate -9DW study results, which were shared at several notable conferences, including the 2024 American Society of Oncology Annual Meeting, the 2024 European Society for Medical Oncology Congress, and the 2025 ASCO Gastrointestinal Cancers Symposium. The research demonstrated that the combination of Opdivo plus Yervoy led to a statistically significant improvement in overall survival, the primary endpoint of the study. In the trial, patients receiving Opdivo and Yervoy had a median overall survival of 23.7 months, compared to 20.6 months for those treated with lenvatinib or sorafenib, indicating a clear survival benefit across different patient subgroups.

In addition to overall survival, the trial reported an impressive overall response rate: 36.1% for patients treated with Opdivo plus Yervoy, in contrast to 13.2% for those receiving lenvatinib or sorafenib. The dual therapy showed a more profound response, and the safety profile remained consistent with previous data, with no new safety concerns arising.

This EC approval is applicable across all 27 member states of the European Union, as well as Iceland, Liechtenstein, and Norway. Furthermore, Opdivo-based treatments are approved for various tumor types within the EU, underscoring the versatility and effectiveness of these medications.

In a parallel development, the U.S. FDA acknowledged Bristol Myers Squibb’s supplemental Biologics License Application (sBLA) for the Opdivo and Yervoy combination in August 2024, marking it as a potential first-line treatment for adult patients with unresectable HCC. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal date of April 21, 2025. Notably, the combination was granted accelerated approval in 2020 by the U.S. FDA as a second-line treatment for advanced HCC, based on the Phase 2 CheckMate -040 trial results.

The CheckMate -9DW trial itself was a Phase 3 randomized, open-label study assessing the efficacy of Opdivo plus Yervoy against the investigator’s choice of lenvatinib or sorafenib monotherapy in adults with unresectable or advanced hepatocellular carcinoma, who had not previously received systemic therapy. The trial involved 668 patients randomized to either the combination treatment or single-agent lenvatinib or sorafenib. The primary focus was on overall survival, with secondary endpoints including objective response rate and time to symptom deterioration.

Overall, this approval signifies a pivotal advancement in the treatment landscape for hepatocellular carcinoma, offering new hope to patients and reinforcing the potential of immunotherapy to transform cancer care.