Opdualag was approved for unresectable/metastatic melanoma | LAG-3 inhibitors | Mode of action

Bristol Myers Squibb announced that the European Commission had approved Opdualag (nivolumab and relatlimab) for treating advanced melanoma as first-line therapy in patients with <1% PD-L1 expression in adults and adolescents of 12 years and older.


Nivolumab was a PD-1 inhibitor, and relatlimab was a LAG-3-blocking antibody. Opdualag is the first fixed-dose immunotherapy approved for melanoma.

The approval was based on the Phase 2/3 RELATIVITY-047 trial, which recruited patients with <1% PD-L1 expression. The fixed-dose combination has more than doubled the progression-free survival compared to nivolumab monotherapy. Further, no new safety events were observed compared to nivolumab monotherapy.

The median progression-free survival was 6.7 months in patients on Opdualag versus 3.0 months in patients on nivolumab monotherapy. The median overall survival in patients on Opdualag was not reached at the time of analysis.

BMS announced that it is evaluating relatlimab in combination with other drugs for different cancers.




How do LAG-3 inhibitors work?

T-cells are the white blood cells involved in fighting foreign bodies and unhealthy cells. Lymphocyte-activation gene 3 (LAG-3) is a checkpoint receptor protein involved in the activation and growth of T cells. It is an inhibitory receptor that prevents T-cell attacks on normal cells.

Prolonged exposure to cancer cells will exhaust the T cells, thereby inactivating T cells and reducing the immune response. In this case, there will be an increase in the production of LAG-3 inhibitors.

Inhibition of LAG-3 helps restore T cells' function, thereby promoting anti-tumor activity.


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