Patients in the European Union with advanced melanoma can now get a two-in-one immunotherapy. The European Commission approved Opdualag, Bristol Myers Squibb announced in mid-September 2022, for first-line treatment in adults and adolescents aged 12 and older.
The approval covers disease that cannot be removed by surgery or has spread, in patients whose tumor cells show PD-L1 expression below 1%.
Two antibodies in one infusion
Here’s what is in it. Opdualag combines nivolumab, which blocks PD-1, with relatlimab, a new antibody that blocks a second immune checkpoint called LAG-3. Both go in together as a fixed-dose combination, and Bristol Myers Squibb calls it a first-in-class treatment.
Think of it like taking off two parking brakes rather than one. LAG-3 sits on T cells and helps rein in their response, activation and growth. Lab studies suggest that blocking it may bring worn-out T cells back to working order and give the body a better shot at attacking the tumor.
It is also the first approved LAG-3-blocking antibody combination for advanced melanoma in the EU. “The RELATIVITY-047 study demonstrated the important benefit of inhibiting both LAG-3 and PD-L1,” said Samit Hirawat, M.D., the company’s chief medical officer for Global Drug Development.
What the trial showed
The decision rests on an exploratory analysis of RELATIVITY-047, limited to patients with that low PD-L1 level. In that group, median progression-free survival was 6.7 months on Opdualag. Patients on nivolumab alone had 3.0 months. The hazard ratio was 0.68. Median overall survival in the Opdualag arm had not yet been reached.
The trial also met its primary endpoint of progression-free survival in the all-comer population.
Side effects were common. Fatigue was the most frequent adverse reaction, at 41%, followed by musculoskeletal pain at 32% and rash at 29%. Serious reactions included adrenal insufficiency at 1.4%, anemia at 1.4% and myocarditis at 1.1%. Grade 3-5 adverse reactions hit 43% of patients on Opdualag, against 35% of those on nivolumab alone.
Why melanoma
Melanoma starts in the pigment-producing cells of the skin. When it spreads to other organs it becomes the deadliest form of the disease. Cases have climbed steadily for the last 30 years. In the United States, 106,110 new diagnoses and about 7,180 deaths were estimated for 2021. The World Health Organization projects that by 2035 melanoma incidence will reach 424,102, with 94,308 related deaths.
Caught early, melanoma is mostly treatable. Survival drops as it progresses.
Bristol Myers Squibb is testing relatlimab in other combinations across a variety of tumor types. The marketing authorization does not extend to Great Britain, meaning England, Scotland and Wales.
