The European Commission has approved the fixed-dose combination of nivolumab and relatlimab for the first-line treatment of advanced (unresectable or metastatic) melanoma in adults and adolescents aged 12 years and older with tumor PD-L1 expression. <1%. Bristol Myers Squibb reports.
The decision of the EU Commission – reads a company note – is based on an exploratory analysis of the results of the global phase 2/3 study ‘Relativity-047’, randomized, double-blind in patients with tumor expression <1 %, which showed that treatment with the fixed-dose combination of nivolumab, a PD-1 inhibitor, and relatlimab, a new antibody that blocks LAG-3, more than doubled median progression-free survival (Pfs) compared to nivolumab monotherapy - an established standard of care. No new safety signals were identified with the combination versus nivolumab monotherapy.
“The fixed-dose association of nivolumab and relatlimab – says Samit Hirawat, executive vice president, chief medical officer, Global drug development, in Bristol Myers Squibb – is now the first association of nivolumab with an anti-LAG-3 antibody, relatlimab, approved in the European Union for advanced melanoma. The Relativity-047 study demonstrated the important advantage of inhibiting both LAG-3 and PD-1 with our new immunotherapy combination. It is the continuation of our commitment to offer innovative drugs to adults and adolescents suffering from melanoma. We thank all the patients, researchers and physicians who contributed to these advances and who made today’s approval possible ”.
The European Commission decision affects all EU member states, as well as Iceland, Liechtenstein and Norway.The centralized marketing authorization does not include approval in Great Britain. The indication in the EU is based on exploratory data analysis from the Relativity-047 study in patients with tumor PD-L1 expression <1%. From an efficacy perspective, the median progression-free survival was 6.7 months in patients treated with the fixed-dose combination of nivolumab and relatlimab compared to 3.0 months in patients treated with nivolumab alone. Median overall survival in the fixed dose combination arm of nivolumab and relatlimab was not achieved. On the safety front, however, the most common adverse reactions - continues the note - were fatigue (41%), musculoskeletal pain (32%), skin rash (29%), arthralgia (26%), diarrhea (26%), itching (26%), headache (20%) and nausea (19%). The incidence of Grade 3-5 adverse reactions was 43% for patients treated with the fixed-dose combination of nivolumab and relatlimab compared to 35% for patients treated with nivolumab alone. The Relativity-047 study also met the primary endpoint of progression-free survival in the entire observed population.
Lymphocyte activation gene 3 (LAG-3) is a surface molecule expressed on effector and regulatory T cells (Treg) and functions by controlling T cell response, activation and growth. Initial research shows that targeting the LAG-3 pathway in combination with other potentially complementary immune pathways may prove to be a key strategy to more effectively enhance anti-tumor immune activity.
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when the cancer spreads beyond the surface of the skin to other organs. Its incidence has steadily increased over the past 30 years. In the United States, 106,110 new melanoma diagnoses and approximately 7,180 related deaths were estimated in 2021. Globally, WHO estimates that, by 2035, the incidence of melanoma will reach 424,102, with 94,308 related deaths. Melanoma is for the most part treatable when treated in the early stages; however, survival rates decline as the disease progresses.