BMS Submits BLA for Fixed-Dose Relatlimab (LAG-3) + Nivolumab (PD-1) Combination Therapy with FDA Granting Priority Review

Source: PharmaCube Info

On September 20, BMS announced that the FDA has accepted the marketing application for the fixed-dose combination of relatlimab (LAG-3) and nivolumab (PD-1) for the treatment of adults and adolescents aged 12 years and older (weighing ≥40 kg) with unresectable or metastatic melanoma, with a PDUFA goal date of March 19, 2022.

Lymphocyte-activation gene 3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are typically co-expressed on tumor-infiltrating lymphocytes (TILs) and lead to tumor-mediated T cell exhaustion. Combination therapy with the novel LAG-3-blocking antibody relatlimab and the PD-1 inhibitor nivolumab can activate T cells, thereby eliciting an enhanced immune response and promoting tumor cell death.

On May 19 this year, Bristol-Myers Squibb (BMS) announced the clinical trial data from the Phase II/III RELATIVITY-047 study. The results demonstrated that, in patients with previously untreated metastatic or unresectable melanoma, the fixed-dose combination of relatlimab and nivolumab as first-line therapy achieved a statistically and clinically significant progression-free survival (PFS) benefit compared with Opdivo monotherapy (10.12 vs. 4.63 months; HR = 0.75; 95% CI: 0.62–0.92; p = 0.0055). This marks the first presentation of Phase III clinical trial data for an anti-LAG-3 antibody, as well as the first treatment regimen to demonstrate statistical superiority over anti-PD-1 antibody monotherapy in metastatic melanoma.

The safety profile of the fixed-dose combination therapy of relatlimab and Opdivo was manageable, consistent with previous reports. Compared with Opdivo monotherapy, no new safety signals or clinically significant events were observed with the combination therapy. The incidence of Grade 3/4 treatment-related adverse events was 18.9% in the combination group and 9.7% in the Opdivo group. The proportion of patients discontinuing treatment due to treatment-related adverse events was 14.6% in the combination group and 6.7% in the monotherapy group.

If this combination therapy is approved, relatlimab will become the third class of immune checkpoint inhibitors to reach the market, following CTLA-4 and PD-1/PD-L1.