BMS study of Opdualag in adjuvant melanoma ends in failure

Bristol Myers Squibb has reported disappointing results for its checkpoint inhibitor combination Opdualag in melanoma, dashing its hopes of moving the drug earlier in the treatment pathway.

Opdualag – which combines the PD-1 inhibitor nivolumab in BMS' blockbuster cancer drug Opdivo with LAG-3 inhibitor relatlimab – was unable to improve on Opdivo alone in the RELATIVITY-098 study, which enrolled people with stage III-IV melanoma that had been completely surgically removed.

Opdualag did not perform significantly better than Opdivo on the primary endpoint of recurrence-free survival (RFS) when used as adjuvant (post-surgery) therapy to try to prevent the cancer from coming back, according to a company statement.

Jeffrey Watch, head of the Opdualag development programme at BMS, said one possible reason for the disappointing result is that patients whose tumours are completely removed in surgery "may not have sufficient antitumour T-cells in place for Opdualag to have its maximal effect."

Checkpoint inhibitors like nivolumab and relatlimab act by removing a brake on the activity of T-cells against tumour cells, encouraging the body to mount an immune response against the cancer.

Opdualag was the first drug in the LAG-3 class to get FDA approval in 2022 and sales in its first indication of first-line treatment of unresectable or metastatic melanoma have grown steadily since then and look set to broach the blockbuster threshold this year.

In 2024, Opdualag grew by a solid 48% to $928 million, although, it remains dwarfed by sales of Opdivo, which came in at $9.3 billion. Opdivo is heading for patent expiry in the next few years, likely around 2028, and – given Opdualag is one of the drugs intended to step into its shoes after biosimilar competition starts – the failed trial comes as a blow to the drugmaker.

While Opdivo has a list of indications as long as your arm, extending the uses of Opdualag has proved to be more challenging, with a phase 3 trial scrapped in microsatellite-stable (MSS) colorectal cancer towards the end of 2023.

Other than the adjuvant melanoma study, other late-stage trials in BMS' current pipeline listing that mention the LAG-3 inhibitor include RELATIVITY-1093 in first-line non-small cell lung cancer (NSCLC) with PD-L1 expression of 1% or more – which would be a much larger potential market – and a first-line melanoma study involving a subcutaneous formulation of nivolumab and relatlimab as first-line therapy for the skin cancer.

In its statement on the RELATIVITY-098 study, the company says that it is evaluating relatlimab "in clinical trials in combination with other agents in a variety of tumour types."

Meanwhile, competition in the LAG-3 category could be on the way from Immutep, whose eftilagimod alfa (efti) was shown to boost the activity of MSD's PD-1 inhibitor Keytruda (pembrolizumab) in PD-L1-negative head and neck cancer last year, which the company said could potentially support regulatory filings.

MSD's own efforts in this area hit the buffers last December, however, when it stopped development of its anti-LAG-3 antibody favezelimab after a negative readout in PD-L1-positive MSS metastatic colorectal cancer.

Photo by Donald Giannatti on Unsplash