BMS Defends Opdualag's Future After Adjuvant Melanoma Setback

Highlights

• Opdualag failed to improve recurrence-free survival compared to Opdivo alone in the adjuvant treatment of stage 3 and 4 melanoma in the Relativity-098 trial.
• Both arms showed approximately 39% recurrence or death rate with no statistically significant difference at 23.4 months median follow-up.
• Opdualag was linked to a higher rate of severe adverse events (19%) and two treatment-related deaths.
• The failure in resected melanoma raises doubts about the clinical utility of LAG-3 targeting antibodies in this setting.
• BMS CMO Dr. Samit Hirawat stressed that these results do not impact the ongoing development of Opdualag in metastatic NSCLC, where tumor presence and PD-1 expression levels influence treatment benefit.
• Relativity-104 phase 2 data in NSCLC showed mixed results, with some subgroups benefiting, leading to the launch of the phase 3 Relativity-1093 trial.
• Criticism persists over BMS' interpretation of NSCLC data, but the company remains committed to advancing Opdualag in lung cancer.

Opdualag Fails to Improve Outcomes in Adjuvant Melanoma

Bristol Myers Squibb (BMS) disclosed full results from the Phase 3 Relativity-098 trial at the 2025 American Society of Clinical Oncology (ASCO) meeting, confirming that its fixed-dose combination immunotherapy, Opdualag—a regimen combining Opdivo (nivolumab) and the LAG-3 antibody relatlimab—did not show benefit as an adjuvant treatment for patients with completely resected stage 3 and 4 melanoma.

With a minimum follow-up of 23.4 months, Opdualag demonstrated no significant difference compared to Opdivo alone regarding risk of disease recurrence or death. Approximately 39% of patients in both treatment arms had experienced recurrence or passed away by the analysis time point.

At two years, 62% of patients receiving Opdualag remained alive without recurrence, versus 63.6% of patients treated with Opdivo alone. The median recurrence-free survival was not reached in the Opdualag group but was 33.1 months for the control group. However, Opdualag was associated with a higher incidence of severe (grade 3 or 4) treatment-related adverse events—19% compared to 8% in the Opdivo-only group—and reported two treatment-related deaths versus one in the control arm.

Questions Raised Over LAG-3 Antibody Utility

This negative outcome reignites skepticism surrounding the clinical value of LAG-3 antibodies in the adjuvant melanoma setting and calls into question BMS' strategic choice last year to advance a higher dose of relatlimab combined with Opdivo into phase 3 testing for first-line treatment of non-small cell lung cancer (NSCLC).

Nevertheless, BMS Chief Medical Officer Dr. Samit Hirawat emphasized that results from adjuvant melanoma should not be extrapolated to metastatic NSCLC, where the tumor microenvironment differs significantly. Hirawat explained that relatlimab enhances immune activation synergistically with Opdivo when a tumor is present by attracting T cells to the site of disease.

In contrast, the Relativity-098 trial involved patients with resected melanoma who had no detectable tumor at the time of treatment, which may account for the lack of added benefit.

NSCLC Trials and Ongoing Confidence in Opdualag

Dr. Hirawat pointed to data from the phase 2 Relativity-104 trial in metastatic NSCLC, noting that patients with PD-1 expression greater than 1% showed clinical benefit from the Opdualag combination. Although the trial fell short of impressing in an all-comers first-line NSCLC population, BMS highlighted improved outcomes in nonsquamous patients with PD-L1 expression between 1% and 49%. This subgroup data supported BMS' decision to proceed with the phase 3 Relativity-1093 trial, later amended to include all PD-L1-positive patients after further evaluation of PD-L1-high data.

Critics have questioned BMS' approach, arguing that the company's attempts to identify positive signals by focusing on narrower patient populations risked overinterpretation. Additionally, concerns arose because the control arm in the phase 2 trial performed worse than historical expectations, casting doubt on the robustness of the observed benefits.

Despite these criticisms and the recent adjuvant melanoma setback, Dr. Hirawat reaffirmed BMS' confidence in continuing the first-line NSCLC study with Opdualag.