Bristol Myers Squibb made history in March by introducing the first LAG-3 drug as part of an Opdivo combo called Opdualag. As the first in a new cancer immunotherapy class, Opdualag now has additional data to back its use in various melanoma patients.
Compared with single-agent Opdivo, Opdualag’s benefits in key patient subgroups were “generally consistent” with the outcomes from the overall population of a phase 3 melanoma trial, Mark Rutstein, M.D., vice president of Opdivo development at BMS, said in an interview with Fierce Pharma.
Rutstein’s description covered patients divided by PD-L1 and LAG-3 expressions, by BRAF mutations and by baseline levels of the enzyme lactate dehydrogenase, a prognostic factor. The data, from the Relativity-047 trial, will be presented at the American Society of Clinical Oncology 2022 annual meeting.
Opdualag earned its FDA approval in melanoma based on Relativity-047 data showing it could pare down the risk of disease progression or death by 25% over Opdivo alone.
Because Opdualag adds anti-LAG-3 antibody relatlimab to Opdivo, people might suspect that Opdualag’s benefit was only for those patients whose tumors expressed LAG-3. But that doesn’t seem to be the case in Relativity-047.
In patients who had tumor LAG-3 expression at or above 1%, Opdualag cut the risk of disease progression or death by 20% over Opdivo, Rutstein said. And the reduction was 28% in those with LAG-3 expression below 1%.
Targeted therapies such as Novartis’ combo of Tafinlar and Mekinist are currently used as standard of care for newly diagnosed melanoma patients with certain BRAF mutations. Opdualag's use in patients with or without BRAF mutations showed comparable results in terms of disease progression or life extension, Rutstein said.
Opdualag reduced the disease progression or death risk by 23% among patients with BRAF-mutant tumors and by 22% in patients with normal BRAF. He also described the tumor response rate and the overall survival data as similar in both subgroups.
Rutstein did note “some variability” in Opdualag’s showing in a couple subgroups, where the evidence of benefit appeared stronger for some patients. For example, in PD-L1 expressors, for whom PD-1 inhibitors like Opdivo typically work better than in PD-L1 nonexpressors, patients had roughly the same risk of disease progression or death between Opdualag and Opdivo. But in patients with PD-L1 less than 1%, Opdualag offered a 32% risk reduction in progression-free survival.
Like drugmakers would typically do, Rutstein noted the analyses of small subgroups aren’t conclusive because they don’t bear statistical power. What’s more, Opdualag did reduce the risk of death by 16% in those with PD-L1 of at least 1% and showed an improvement of 8 percentage points in tumor shrinkage rate, he said.
Overall, Rutstein argued that the new data showed consistency in the trial endpoints across patient subgroups.
Although Opdualag showed wide-ranging benefits, Rutstein wouldn’t say that Opdivo is particularly weak in any patient groups, only stressing that they’re offering patients more options.
Opdualag comes with a cleaner safety profile than Bristol Myers’ other dual-immunotherapy regimen that pairs Opdivo with CTLA-4 inhibitor Yervoy. The company is counting on Opdualag's improved tolerability to convince more doctors to use a doublet.