Summary of Clinical Use

Relatlimab (BMS-986016) was advanced to clinical trial in solid tumours and haematological malignancies. It was evaluated in combination with other immune checkpoint inhibitors (nivolumab, ipilimumab) and/or selected kinase inhibitor chemotherapeutics (dasatinib, cobimetinib), and/or other monoclonals (daratumumab). Relatlimab, in combination with nivolumab was granted FDA orphan drug designation for the treatment of advanced melanoma [4] in 2019, and as Opdualag® this combination was FDA approved in March 2022 as a therapy for unresectable/metastatic melanoma. EMA authorisation of Opdualag® followed in September 2022.

Mechanism Of Action and Pharmacodynamic Effects

Membrane-bound LAG-3 is expressed on activated T cells and is upregulated on exhausted T cells, and is also found on activated Treg cells [1,3]. Antibody-mediated LAG-3 blockade may therefore inhibit the suppressive effects of Tregs in addition to promoting effector T-cell function. This dual effect makes for a promising approach for immunotherapy/immuno-oncology.

Clinical Trials
Clinical Trial ID	Title	Type	Source	Comment	References
NCT03470922	A Study of Relatlimab Plus Nivolumab Versus Nivolumab Alone in Participants With Advanced Melanoma	Phase 2/Phase 3 Interventional	Bristol-Myers Squibb	RELATIVITY-047 study; comparing relatlimab monotherapy against relatlimab + nivolumab as first-line therapy for metastatic or unresectable melanoma.