FDA Accepts Priority Review Application for Relatlimab, Nivolumab Combination in Unresectable, Metastatic Melanoma

Officials with the FDA have accepted a Priority Review application for a fixed-dose combination of relatlimab and nivolumab in patients with unresectable or metastatic melanoma, according to a press release from Bristol Myers Squibb.

The application is based on findings from the phase 2/3 RELATIVITY-047 trial, which found a statistically significant and clinically meaningful progression-free survival (PFS) benefit for the combination compared to monotherapy with nivolumab. The FDA set a target action date for March 19, 2022.

Relatlimab is a lymphocyte-activation gene 3 (LAG-3)-blocking antibody that is being investigated with other agents in a variety of tumor types. LAG-3 is a cell-surface molecule found on effector T cells and regulatory T cells, and it works to control T cell response, activation, and growth. Preclinical studies suggest that inhibiting LAG-3 could restore effector function of exhausted T cells and could potentially promote an anti-tumor response.

The RELATIVITY-047 trial is a global, randomized, double-blind phase 2/3 study evaluating the combination of relatlimab and nivolumab in patients with previously untreated metastatic or unresectable melanoma compared with nivolumab alone. The primary endpoint is PFS, and the secondary endpoints are overall survival (OS) and objective response rate (ORR).

In the study, a total of 714 patients were randomized 1:1 to receive either nivolumab 480 mg or a fixed-dose combination of relatlimab 160 mg and nivolumab 480 mg by intravenous infusion every 4 weeks until disease recurrence, unacceptable toxicity, or withdrawal of consent. Follow-up for the secondary endpoints of OS and ORR is ongoing.

“Although we’ve seen significant advances in the treatment of melanoma since the introduction of immune checkpoint inhibitors, there continue to be patients who could benefit from a novel dual immunotherapy approach,” said Jonathan Cheng, MD, senior vice president and head of oncology development at Bristol Myers Squibb, in the press release. “Based on the results of the RELATIVITY-047 trial, we believe that the relatlimab and nivolumab fixed-dose combination has the potential to improve outcomes for patients with metastatic or unresectable melanoma.”

The Biologics License Application is based on efficacy and safety results from the phase 2/3 RELATIVITY-047 trial, which found a statistically significant and clinically meaningful PFS benefit with the combination therapy in metastatic melanoma. Relatlimab is the first LAG-3-blocking antibody to demonstrate a clinical benefit for patients with phase 3 data, and primary results from the trial were presented during the American Society of Clinical Oncology (ASCO) Annual Meeting in June 2021.

REFERENCE

US Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for LAG-3-Blocking Antibody Relatlimab and Nivolumab Fixed-Dose Combination as Treatment for Patients with Unresectable or Metastatic Melanoma. News release. Bristol Myers Squibb; September 20, 2021. Accessed September 20, 2021. https://news.bms.com/news/corporate-financial/2021/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibbs-Application-for-LAG-3-Blocking-Antibody-Relatlimab-and-Nivolumab-Fixed-Dose-Combination-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx