Opdivo plus Yervoy Shows Survival Benefit in Patients with Hepatocellular Carcinoma in Phase III CheckMate -9DW Trial

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First-line combination immunotherapy with Opdivo (nivolumab) plus Yervoy (ipilimumab) achieved the primary endpoint of overall survival (OS) in the Phase III CheckMate -9DW trial among patients with advanced hepatocellular carcinoma (HCC).¹ Opdivo plus Yervoy was found to produce a statistically significant and clinically meaningful OS improvement vs. investigator’s choice of sorafenib or lenvatinib at a pre-specified interim analysis.

“Advanced stage liver cancer patients remain in need of additional treatment options that may help improve survival,” Dana Walker, MD, MSCE, vice president, global program lead, gastrointestinal and genitourinary cancers, Bristol Myers Squibb, said in a press release. “The overall survival benefit demonstrated by the combination of Opdivo plus Yervoy in the CheckMate -9DW trial demonstrates its potential to improve outcomes compared to well-established (tyrosine kinase inhibitor [TKI]) treatment options.”¹

Opdivo is a monoclonal antibody that binds to the PD-1 receptor and inhibits tumor growth by improving T-cell function.^2,3 Opdivo has been approved across an array of indications, both as a single agent and in combination therapy, including for patients with unresectable or metastatic melanoma; metastatic NSCLC; advanced renal cell carcinoma; classical Hodgkin lymphoma; recurrent or metastatic squamous cell carcinoma of the head and neck; locally advanced or metastatic urothelial carcinoma; microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer; and hepatocellular carcinoma.²

Yervoy is a recombinant, human monoclonal antibody that attaches to the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), which is a negative T-cell activity regulator. By attaching to CTLA-4, Yervoy inhibits the interaction between CTLA-4 and its CD80/CD86 ligands. This action has been found to increase T-cell activation and proliferation, including tumor-infiltrating T-effector cells.

The FDA initially approved Yervoy 3 mg/kg monotherapy on March 25, 2011, for patients with unresectable or metastatic melanoma. The drug has since been approved for unresectable or metastatic melanoma in more than 50 countries.¹

HCC is the most common form of primary liver cancer, comprising approximately 90% of all liver cancer cases. The disease is frequently diagnosed at the advanced stage, with limited effective treatment options.¹

The Phase III randomized, open-label CheckMate -9DW trial is analyzing Opdivo plus Yervoy compared to investigator’s choice of sorafenib or lenvatinib monotherapy in patients with advanced HCC were not previously administered a systemic therapy.

Investigators randomly assigned approximately 668 patients to receive Opdivo 1mg/kg plus Yervoy 3 mg/kg every three weeks for up to four doses, followed by Opdivo monotherapy 480 mg every four weeks via infusion, compared with single agent sorafenib or lenvatinib as oral capsules in the control cohort. The trial’s primary endpoint is OS, with key secondary endpoints that include objective response rate and time to symptom deterioration.

In terms of safety, there were no new signals identified for the Opdivo plus Yervoy combination, with a profile that was consistent with prior findings and manageable with established protocols.

Bristol Myers Squibb said it will complete a full evaluation of the data and share the findings at an upcoming medical conference, in addition to discussing with health authorities.

References

1. Bristol Myers Squibb Announces CheckMate -9DW Trial Evaluating Opdivo (nivolumab) Plus Yervoy (ipilimumab) Meets Primary Endpoint of Overall Survival for the First-Line Treatment of Advanced Hepatocellular Carcinoma. Bristol Myers Squibb. News release. March 20, 2024. Accessed March 20, 2024. https://news.bms.com/news/details/2024/Bristol-Myers-Squibb-Announces-CheckMate--9DW-Trial-Evaluating-Opdivo-nivolumab-Plus-Yervoy-ipilimumab-Meets-Primary-Endpoint-of-Overall-Survival-for-the-First-Line-Treatment-of-Advanced-Hepatocellular-Carcinoma/default.aspx

2. Opdivo. Prescribing information. Bristol Myers Squibb; 2021. Accessed March 20, 2024. https://packageinserts.bms.com/pi/pi_opdivo.pdf

3. FDA approves first immunotherapy for initial treatment of gastric cancer [News release].FDA. April 16, 2021. Accessed March 20, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-immunotherapy-initial-treatment-gastric-cancer.