"Bristol Myers Squibb announced that the European Commission (EC) has approved Opdivo (nivolumab) plus Yervoy (ipilimumab) for the first-line treatment of adult patients with unresectable or advanced hepatocellular carcinoma (HCC).
“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 US 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 US FDA in 2020 based on results from the Phase 2 CheckMate -040 trial.
Bristol Myers Squibb thanks the patients and investigators for their important contributions to the Phase 3 CheckMate -9DW clinical trial.
CheckMate -9DW is a phase 3 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.
Liver cancer is the third most frequent cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for 90% of global cases. HCC is often diagnosed at an advanced stage, where effective treatment options are limited and are usually associated with poor outcomes.
Up to 70% of patients experience recurrence within five years, particularly those still considered to be at high risk after surgery or ablation. While most cases of HCC are caused by hepatitis B virus or hepatitis C virus infections, metabolic syndrome and nonalcoholic steatohepatitis are rising in prevalence and expected to contribute to increased rates of HCC.
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-tumour 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 programme 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 tumour types. To date, the Opdivo clinical development program has treated more than 35,000 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 65 countries, including the United States, the European Union, Japan and China. 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.
Yervoy is a recombinant, human monoclonal antibody that binds to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4). CTLA-4 is a negative regulator of T-cell activity. Yervoy binds to CTLA-4 and blocks the interaction of CTLA-4 with its ligands, CD80/CD86. Blockade of CTLA-4 has been shown to augment T-cell activation and proliferation, including the activation and proliferation of tumour infiltrating T-effector cells. Inhibition of CTLA-4 signalling can also reduce T-regulatory cell function, which may contribute to a general increase in T-cell responsiveness, including the anti-tumour immune response. On March 25, 2011, the US Food and Drug Administration (FDA) approved Yervoy 3 mg/kg monotherapy for patients with unresectable or metastatic melanoma. Yervoy is approved for unresectable or metastatic melanoma in more than 50 countries. There is a broad, ongoing development programme in place for Yervoy spanning multiple tumour types.
In 2011, through a collaboration agreement with Ono Pharmaceutical Co., Bristol Myers Squibb expanded its territorial rights to develop and commercialize Opdivo globally, except in Japan, South Korea and Taiwan, where Ono had retained all rights to the compound at the time. On July 23, 2014, Ono and Bristol Myers Squibb further expanded the companies’ strategic collaboration agreement to jointly develop and commercialize multiple immunotherapies – as single agents and combination regimens – for patients with cancer in Japan, South Korea and Taiwan.
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases.