Relatlimab: A Comprehensive Clinical and Scientific Monograph on the First-in-Class LAG-3 Checkpoint Inhibitor

Executive Summary

Relatlimab is a first-in-class, human immunoglobulin G4 (IgG4) monoclonal antibody that represents a significant advancement in the field of immuno-oncology by targeting the Lymphocyte-Activation Gene 3 (LAG-3) immune checkpoint.[1] Developed by Bristol Myers Squibb (BMS) under the development code BMS-986016, Relatlimab is exclusively marketed as a fixed-dose combination with the established programmed death-1 (PD-1) inhibitor, nivolumab.[3] This combination product, branded as Opdualag, delivers a dual checkpoint blockade strategy in a single intravenous infusion.[5]

The mechanism of action of Relatlimab involves binding to the LAG-3 receptor on exhausted T-cells, thereby blocking its inhibitory signaling pathway. When co-administered with nivolumab, which blocks the separate PD-1 pathway, this dual inhibition synergistically restores T-cell effector function and enhances anti-tumor immunity.[1] This approach is designed to overcome the limitations of single-agent immunotherapy and provide a more robust anti-cancer response.

The cornerstone of Relatlimab's clinical validation is the pivotal Phase 2/3 RELATIVITY-047 trial. In this study, Opdualag demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) compared to nivolumab monotherapy for patients with previously untreated, unresectable or metastatic melanoma.[5] The combination more than doubled the median PFS from 4.6 months with nivolumab alone to 10.1 months with Opdualag, with long-term follow-up confirming the durability of this benefit.[9]