Bristol Myers Squibb's Opdualag Faces Setback in Melanoma Expansion Bid

Bristol Myers Squibb (BMS) has encountered a significant obstacle in its efforts to broaden the application of its first-in-class combination drug, Opdualag. The company recently announced that a phase 3 trial investigating Opdualag as an adjuvant treatment for patients with completely resected stage III and stage IV melanoma failed to meet its primary endpoint.

Trial Results and Implications

The RELATIVITY-098 trial did not demonstrate a significant improvement in recurrence-free survival (RFS) when comparing Opdualag to Opdivo monotherapy. This outcome deals a blow to BMS's strategy to expand Opdualag's reach in melanoma treatment. Currently, Opdualag is approved for patients aged 12 and older with unresectable or metastatic melanoma.

Dr. Jeffrey Walch, BMS's global program lead for Opdualag, expressed disappointment in the trial's outcome, stating, "We are disappointed that LAG-3 inhibition in the adjuvant setting did not lead to the same improved efficacy outcomes seen in advanced melanoma." He suggested that patients whose tumors are completely resected before treatment may not have sufficient antitumor T cells for Opdualag to exert its maximal effect.

Opdualag's Development and Future Prospects

This setback marks the second major clinical defeat for Opdualag, following the termination of a phase 3 trial in metastatic colorectal cancer (mCRC) 14 months ago. Despite these challenges, BMS remains optimistic about Opdualag's potential in other indications, particularly non-small cell lung cancer (NSCLC).

The company is initiating the RELATIVITY 1093 trial, which will evaluate Opdualag plus chemotherapy in patients with stage 4 or recurrent non-squamous NSCLC with PD-L1 expression between 1% and 49%. This trial will employ a higher dose of relatlimab than in the FDA-approved melanoma indication and will use Merck's Keytruda and chemotherapy as the comparator.

Additionally, BMS plans to launch another phase 3 trial this year, focusing on Opdualag in first-line, non-squamous NSCLC patients with PD-L1 expressions of at least 50%.

Market Performance and Competition

Despite the recent setback, Opdualag has shown strong market performance. In 2024, the drug achieved sales of $928 million, representing a 48% increase from the previous year. However, BMS faces potential competition in the LAG-3 inhibitor space, with Regeneron poised to challenge the company using its own LAG-3 inhibitor, fianlimab. Regeneron has already initiated four phase 3 programs combining fianlimab with its PD-1 inhibitor, Libtayo.

As the pharmaceutical landscape continues to evolve, the outcome of these ongoing trials and market dynamics will play a crucial role in shaping the future of LAG-3 inhibitors in cancer treatment.