FDA Approves First-in-Class LAG-3 Inhibitor Opdualag (Relatlimab + Nivolumab) for Unresectable or Metastatic Melanoma

On March 18, Bristol-Myers Squibb (BMS) announced that the FDA had approved the fixed-dose combination of Opdualag (relatlimab + nivolumab, LAG-3 + PD-1) for the treatment of unresectable or metastatic melanoma in adults and pediatric patients aged 12 years and older (weighing ≥40 kg).

Notably, relatlimab is the first LAG-3 antibody approved by the U.S. FDA and the first innovative cancer immunotherapy targeting a new immune checkpoint approved in nearly a decade. Additionally, relatlimab is the third type of immune checkpoint inhibitor to be approved globally, following CTLA-4 and PD-1/PD-L1. Bristol-Myers Squibb is also currently the first company to have three different immune checkpoint inhibitors on the market simultaneously.

Lymphocyte activation gene-3 (LAG-3) and programmed death receptor-1 (PD-1) are two distinct inhibitory immune checkpoints, often co-expressed on tumor-infiltrating lymphocytes (TILs), leading to tumor-mediated T-cell exhaustion. The combination of the novel LAG-3 blocking antibody relatlimab and the PD-1 inhibitor nivolumab can activate T cells, triggering an enhanced immune response and promoting tumor cell death. This FDA approval is primarily based on clinical trial data from the Phase II/III RELATIVITY-047 study. Detailed results of this study were published in The New England Journal of Medicine on January 6.

Data show that, for previously untreated patients with metastatic or unresectable melanoma, the fixed-dose combination of relatlimab + nivolumab as a first-line therapy achieved statistically and clinically meaningful progression-free survival (PFS) benefits compared to Opdivo monotherapy (10.12 vs 4.63 months, HR=0.75; 95% CI: 0.62-0.92, p=0.0055). This is the first treatment regimen demonstrating statistical superiority over anti-PD-1 antibody monotherapy in metastatic melanoma.

Subgroup analysis showed that the median PFS was 12.58 months in the LAG-3 positive (≥1%) population and only 4.83 months in the LAG-3 <1% population for the relatlimab + nivolumab group.

PFS Subgroup Analysis by LAG-3 Expression Levels in the RELATIVITY-047 Study

In terms of safety, grade 3 or 4 treatment-related adverse events (TRAEs) were more common in the combination therapy group, with an incidence rate of 18.9% in the relatlimab + nivolumab treatment group, compared to 9.7% in the NIVO monotherapy group.

RELATIVITY-047 Study Safety Data

Source: WuXi AppTec, PharmaCube