Bristol Myers Squibb Gets EC Approval for Opdivo® + Yervoy® in Advanced Hepatocellular Carcinoma
Bristol Myers Squibb (NYSE: BMY) has announced that the European Commission (EC) has granted approval for the combination of Opdivo® (nivolumab) and Yervoy® (ipilimumab) as a first-line treatment for adult patients with unresectable or advanced hepatocellular carcinoma (HCC).This decision marks a significant step forward for patients with this challenging and often fatal form of liver cancer.
According to Dr. Dana Walker, Vice President and Opdivo Global Program Lead at Bristol Myers Squibb, “The European Commission’s approval for Opdivo plus Yervoy adds to the growing body of evidence demonstrating the value of dual immunotherapy and represents an important new treatment option that may extend survival for patients with hepatocellular carcinoma. This approval marks a critical milestone in our commitment to improving outcomes for patients with liver cancer.”
The approval follows promising results from the Phase 3 CheckMate -9DW clinical trial, which were presented at major medical conferences, including the 2024 American Society of Oncology (ASCO®) Annual Meeting, the 2024 European Society for Medical Oncology Congress, and the 2025 ASCO Gastrointestinal Cancers Symposium. The study demonstrated a statistically significant and clinically meaningful improvement in overall survival (OS) for patients treated with Opdivo plus Yervoy compared to the standard of care therapies—lenvatinib and sorafenib.
In the trial, Opdivo plus Yervoy demonstrated a median OS of 23.7 months (95% CI: 18.8–29.4) compared to 20.6 months (95% CI: 17.5–22.5) for the combination of lenvatinib or sorafenib, with a hazard ratio of 0.79 (0.65–0.96; p=0.018). The benefit in survival was observed across various clinically relevant patient subgroups, further supporting the potential of this combination regimen. The trial also showed a significantly higher overall response rate (ORR) of 36.1% (95% CI: 31–41.5) for Opdivo plus Yervoy compared to just 13.2% (95% CI: 9.8–17.3; P<0.0001) for those treated with lenvatinib or sorafenib. This dual immunotherapy approach also led to a deeper response in patients.
The safety profile of Opdivo plus Yervoy remained consistent with previous findings, and no new safety concerns were identified. The combination was well-managed with established treatment protocols, ensuring that the therapy could be safely administered to a wide range of patients.
This approval is applicable in all 27 EU member states, as well as Iceland, Liechtenstein, and Norway. Opdivo-based regimens are also approved across multiple tumor types in the EU, solidifying the broad utility of these immunotherapies in oncology.
The approval of Opdivo plus Yervoy in the first-line setting for HCC in Europe comes shortly after the U.S. Food and Drug Administration (FDA) accepted the supplemental Biologics License Application (sBLA) for this combination, with a Prescription Drug User Fee Act (PDUFA) goal date set for April 21, 2025. Opdivo plus Yervoy was granted accelerated approval as a second-line treatment for patients with advanced HCC in 2020, based on results from the Phase 2 CheckMate -040 trial.
Dr. Walker expressed gratitude toward the patients and investigators who contributed to the CheckMate -9DW trial: “We extend our thanks to the patients and investigators for their invaluable contributions to this pivotal study. Their participation has helped bring us one step closer to improving the prognosis for patients with advanced liver cancer.”
About CheckMate -9DW
The CheckMate -9DW trial is a Phase 3, randomized, open-label clinical study designed to compare the combination of Opdivo and Yervoy with the investigator’s choice of either lenvatinib or sorafenib in patients with unresectable or advanced hepatocellular carcinoma who have not received prior systemic therapy. The trial enrolled 668 patients, with 85% of those in the control arm receiving lenvatinib and 15% receiving sorafenib. The primary endpoint of the study was overall survival, while secondary endpoints included objective response rate (ORR) and time to symptom deterioration. Importantly, the study was not designed to compare Opdivo plus Yervoy against either lenvatinib or sorafenib directly.
About Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is the most common type of liver cancer, representing about 90% of all cases globally. Liver cancer is the third most common cause of cancer-related death worldwide, and HCC often presents at an advanced stage, leaving limited treatment options and poor survival rates. HCC recurrence is a significant concern, with up to 70% of patients experiencing relapse within five years, particularly those still considered at high risk following surgery or ablation. Factors such as hepatitis B and C infections, metabolic syndrome, and nonalcoholic steatohepatitis (NASH) are major contributors to the increasing incidence of liver cancer.
About Opdivo and Yervoy
Opdivo is a PD-1 immune checkpoint inhibitor that works by helping the immune system recognize and attack cancer cells. It has been approved for the treatment of several cancers, including non-small cell lung cancer, melanoma, and renal cell carcinoma, among others. Yervoy is a CTLA-4 inhibitor that enhances T-cell activation by blocking a negative regulator of T-cell activity, contributing to a robust anti-tumor immune response.
Together, Opdivo and Yervoy represent a powerful combination that has shown promise across multiple cancer types, including melanoma, non-small cell lung cancer, and now hepatocellular carcinoma.
The approval of Opdivo plus Yervoy as a first-line treatment option for advanced HCC in Europe is a significant advancement in the field of oncology, providing a new therapeutic option that may extend survival and improve quality of life for patients facing this difficult diagnosis.
