Bristol Myers Squibb  announced that the U.S. Food and Drug Administration (FDA) approved Opdivo^® (nivolumab) plus Yervoy^® (ipilimumab) as a first-line treatment for adult patients with unresectable or metastatic hepatocellular carcinoma (HCC), the most common primary liver cancer.This approval is based on the results from the global Phase 3 randomized, open-label CheckMate-9DW trial evaluating the combination of Opdivo plus Yervoy compared to investigator’s choice of tyrosine kinase inhibitor monotherapy (lenvatinib or sorafenib) in patients with unresectable or metastatic HCC who have not received prior systemic therapy. In the trial, Opdivo plus Yervoy demonstrated statistically significant overall survival (OS) and overall response rate (ORR) vs the comparator arm.¹ It is the only trial supporting an FDA approval to show superior results against this comparator arm.¹

MEDIA: @US_FDA approves first-line immunotherapy treatment option for certain patients with hepatocellular carcinoma.

“The CheckMate-9DW approval is an important advancement for patients, considering the incidence of liver cancer has tripled in the last four decades, yet prognosis for HCC patients remains poor,” said Aiwu Ruth He, MD, PhD, a CheckMate-9DW study investigator while at MedStar Georgetown University Hospital. “The availability of a new first-line treatment option that demonstrated a deep response can offer adults with this form of liver cancer long-term overall survival and may help address an unmet need.Given the strength of evidence from the trial, especially considering the selection and performance of a strong comparator arm, I believe that Opdivo plus Yervoy has the potential to become a standard of care for the first-line treatment of patients with unresectable or metastatic HCC.”¹

In the CheckMate-9DW trial, in which 85% of patients in the comparator arm were treated with lenvatinib and 15% were treated with sorafenib, mOS with Opdivo plus Yervoy (n=335) was 23.7 months (95% CI: 18.8-29.4) vs. 20.6 months (95% CI: 17.5-22.5) with lenvatinib or sorafenib (n=333; HR=0.79; 95% CI: 0.65-0.96 P=0.0180), reducing the risk of death by 21%.¹ Opdivo plus Yervoy showed an OS rate of 38% at three years vs. 24% with lenvatinib or sorafenib monotherapy.¹ The trial also showed a deeper response with Opdivo plus Yervoy, demonstrating an 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 (complete response 6.9% vs 1.8%; partial response 29.3% vs 11.4%).¹ Longer responses were seen with Opdivo plus Yervoy with a median duration of response (mDOR) of 30.4 months (95% CI: 21.2-NR) and 12.9 months (95% CI: 10.2-31.2) with lenvatinib or sorafenib.¹ DOR is not included in the statistical hierarchical testing and therefore is not a powered endpoint.¹ The safety profile with Opdivo plus Yervoy is well-established and there were no new safety signals identified.⁵

Opdivo plus Yervoy is associated with the following Warnings and Precautions: severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, other immune-mediated adverse reactions; infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation (HSCT); embryo-fetal toxicity; and increased mortality in patients with multiple myeloma when Opdivo is added to a thalidomide analogue and dexamethasone, which is not recommended outside of controlled clinical trials.¹ Please see the Important Safety Information section below.

“Bringing Opdivo plus Yervoy to patients with HCC in the first-line setting is a testament to our ongoing commitment to research and delivering important progress for people living with cancer,” said Wendy Short Bartie, senior vice president of Oncology Commercialization at Bristol Myers Squibb. “Today’s approval builds on the legacy of our dual immunotherapy and the value it has brought to patients for years.¹ We are thrilled to add this indication for this important therapy – our second approval for Opdivo plus Yervoy in the gastrointestinal space this week alone – and look forward to providing a new first-line treatment option to patients in need.^”1

The combination of Opdivo plus Yervoy was previously granted accelerated approval by the U.S. FDA in 2020 based on results from the Phase 1/2 CheckMate-040 trial and has been an established second-line treatment for patients with advanced HCC who were previously treated with sorafenib.¹ Today’s FDA decision converts this existing indication to full approval and expands the indication into the first-line setting based on the results from the CheckMate-9DW trial.¹