FDA approves first LAG-3 antibody therapy

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FDA approves first LAG-3 antibody therapy

On March 18, Bristol-Myers Squibb (BMS) announced that the FDA approved the marketing application of Opdualag (relatlimab + nivolumab, LAG-3 + PD-1) fixed-dose combination combination for the treatment of adults and adolescents over 12 years old (weight ≥ 40kg) unresectable or metastatic melanoma.

It is worth mentioning that relatlimab is the first LAG-3 antibody approved by the US FDA and the first innovative cancer immunotherapy approved for a new immune checkpoint in the past 10 years.

In addition, relatlimab is the third class of immune checkpoint inhibitors approved globally after CTLA-4 and PD-1/PD-L1. BMS is also the first company to list three different immune checkpoint inhibitors at the same time.

Lymphocyte-activating gene-3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are commonly co-expressed on tumor-infiltrating lymphocytes (TILs) and contribute to tumorigenesis mediated T cell exhaustion.

Combination treatment with the novel LAG-3-blocking antibody relatlimab and the PD-1 inhibitor nivolumab activates T cells, triggering an improved immune response and promoting tumor cell death.

The FDA approval is based primarily on clinical trial data from the Phase II/III RELATIVITY-047 study. Detailed results of the study were published Jan. 6 in the New England Journal of Medicine.

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

FDA approves first LAG-3 antibody therapy

Subgroup analysis showed that the median PFS of the patient population with positive LAG-3 expression (≥1%) in the relatlimab+nivolumab group was 12.58 months, while the median PFS of the patient population with LAG-3 expression <1% was only 4.83 months. moon.

FDA approves first LAG-3 antibody therapy

Subgroup analysis of PFS 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 arm, with an incidence of 18.9% in the relatlimab+nivolumab arm and 9.7% in the NIVO monotherapy arm.

FDA approves first LAG-3 antibody therapy