Opdualag Misses Primary Endpoint in Phase III RELATIVITY-098 Trial for Melanoma
Results from the RELATIVITY-098 trial of Opdualag in the adjuvant treatment of completely resected stage III-IV melanoma did not meet the primary endpoint of recurrence-free survival.
Credit: Ocskay Mark | stock.adobe.com
The Phase III RELATIVITY-098 trial (NCT05002569) of Opdualag (nivolumab and relatlimab-rmbw) in the adjuvant treatment of completely resected stage III-IV melanoma fell short of the primary endpoint of recurrence-free survival (RFS).1,2
Data regarding the secondary endpoints, which included overall survival and distant metastasis-free survival, were not yet released; however, for the secondary endpoint of safety, the results were consistent with the previously established profiles of both nivolumab and relatlimab.
“We are disappointed in the outcome of the RELATIVITY-098 trial and that (lymphocyte activation gene-3 [LAG-3]) inhibition in the adjuvant setting did not lead to the same improved efficacy outcomes seen in advanced melanoma,” Jeffrey Walch, MD, PhD, vice president, Opdualag global program lead, Bristol Myers Squibb, said in a press release.1
Nivolumab, sold under the brand name Opdivo, is a human IgG4 monoclonal PD-1 blocking antibody. The drug attaches to the PD-1 receptor to block the interaction with its ligands PD-L1 and PD-L2, and decrease PD-1 pathway-mediated inhibition of the immune response.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 non-small cell lung cancer; 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.
Relatlimab is a human IgG4 monoclonal LAG-3 blocking antibody. The drug attaches to the LAG-3 receptor to block the interaction with its ligands, thereby lowering LAG-3 pathway-mediated inhibition of the immune response to promote cytokine secretion and T-cell proliferation.3
Opdualag has been found to increase T-cell activation compared to treatment with each individual medication. The FDA approved Opdualag in March 2022 to treat patients aged 12 years and older with unresectable or metastatic melanoma.4
Trial Design
The randomized, double-blind RELATIVITY-098 trial compared adjuvant immunotherapy with Opdualag vs. Opdivo monotherapy after complete resection of stage III-IV melanoma.
Eligibility criteria included diagnosis of stage IIIA/B/C/D or stage IV melanoma by American Joint Committee on Cancer v8 criteria with complete resection of histologically confirmed melanoma with negative margins.
Patients aged 18 years or older were required to have an ECOG performance status score of 0 or 1, whereas patients aged 12 to 17 years were required to have a Lansky/Karnofsky performance score of 80% or higher. Further, complete resection was required to have occurred within 90 days before randomization; all patients were required to have disease-free status by complete physical examination within 14 days to randomization; and tumor tissue must have been available for biomarker analysis.
Detailed data from the trial were not yet released. Walch added that Opdualag is the standard of care in the adjuvant setting for patients 12 years of age and older with completely resected stage IIB, stage IIC, stage III, or stage IV melanoma.
“Patients whose tumors are completely resected before treatment may not have sufficient antitumor T cells in place for Opdualag to have its maximal effect,” he said in the release. “However, Opdualag remains a standard of care in the first-line treatment of unresectable or metastatic melanoma, and we continue to explore its potential across tumor types, including in non-small cell lung cancer.”1
References
1. Bristol Myers Squibb Provides Update on Phase 3 RELATIVITY-098 Trial. News release. Bristol Myers Squibb. February 13, 2025. Accessed February 28, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Provides-Update-on-Phase-3-RELATIVITY-098-Trial/default.aspx
2. A study to assess adjuvant immunotherapy with nivolumab plus relatlimab versus nivolumab alone after complete resection of stage iii-iv melanoma (RELATIVITY-098). ClinicalTrials.gov. Updated January 20, 2025. Accessed February 28, 2025. https://clinicaltrials.gov/study/NCT05002569
3. Opdualag. Prescribinginformation.Bristol Myers Squibb; 2022. Accessed February 28, 2025. https://packageinserts.bms.com/pi/pi_opdualag.pdf
4. U.S. Food and Drug Administration approves first LAG-3-blocking antibody combination, Opdualag(nivolumab and relatlimab-rmbw), as treatment for patients with unresectable or metastatic melanoma. Bristol-Myers Squibb. News release. March 18, 2022. Accessed February 28, 2025. https://news.bms.com/news/corporate-financial/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx
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