EC Approves Opdivo and Yervoy for Liver Cancer

“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,” said Dana Walker, M.D., M.S.C.E., vice president, Opdivo global program lead, Bristol Myers Squibb. “This approval marks a critical milestone in our commitment to improving outcomes for patients with liver cancer. We look forward to bringing this new first-line treatment option to patients in the European Union.”

The decision is based on results from the CheckMate -9DW study, which were presented at the 2024 American Society of Oncology (ASCO ) Annual Meeting , the 2024 European Society for Medical Oncology Congress and the 2025 ASCO Gastrointestinal Cancers Symposium. Results showed that dual immunotherapy treatment with Opdivo plus Yervoy led to a statistically significant and clinically meaningful improvement in overall survival (OS), the clinical trial’s primary endpoint. In the trial, 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib. The median OS was 23.7 months (95% CI: 18.8–29.4) for Opdivo plus Yervoy compared to 20.6 months (95% CI: 17.5–22.5) with the investigator’s choice of lenvatinib or sorafenib (HR: 0.79 (0.65–0.96); p=0.018). The OS benefit was observed across clinically relevant patient subgroups. The trial also showed an overall response rate (ORR) of 36.1% (95% CI: 31-41.5) compared to 13.2% (95% CI: 9.8-17.3; P<0.0001) of patients treated with lenvatinib or sorafenib and a deeper response with Opdivo plus Yervoy . The safety profile for the combination of Opdivo plus Yervoy remained consistent with previously reported data and was manageable with established protocols, with no new safety signals identified.

This approval by the EC for Opdivo plus Yervoy for the first-line treatment of adult patients with unresectable or advanced HCC is valid in all 27 member states of the European Union (EU), as well as Iceland, Liechtenstein and Norway. In addition to approval in HCC, Opdivo- based options are also approved for treatment of multiple tumor types in the EU.

In August 2024, the U.S. FDA also accepted the Company's supplemental Biologics License Application (sBLA) for Opdivo plus Yervoy as a potential first-line treatment option for adult patients with unresectable HCC and assigned a Prescription Drug User Fee Act (PDUFA) goal date of April 21, 2025. The combination of Opdivo plus Yervoy was granted accelerated approval as a second-line treatment for patients with advanced HCC by the U.S. FDA in 2020 based on results from the Phase II CheckMate -040 trial.

CheckMate -9DW is a Phase III randomized, open-label clinical trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of lenvatinib or sorafenib monotherapy in adult patients with unresectable or advanced hepatocellular carcinoma who have not received prior systemic therapy. A total of 668 patients were randomized to receive Opdivo plus Yervoy ( Opdivo 1mg/kg plus Yervoy 3mg/kg Q3W for up to four doses, followed by Opdivo monotherapy 480mg Q4W) infusion, or single agent lenvatinib or sorafenib taken orally in the control arm. 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib. The primary endpoint of the trial is overall survival (OS) and secondary endpoints include objective response rate (ORR) and time to symptom deterioration. The study was not designed to independently compare Opdivo plus Yervoy vs. lenvatinib or Opdivo plus Yervoy vs. sorafenib.