The Food and Drug Administration has accepted for Priority Review the Biologics License Application for the fixed-dose combination of relatlimab plus nivolumab for the treatment of adult and pediatric patients 12 years of age and older weighing at least 40kg with unresectable or metastatic melanoma.
Relatlimab is a lymphocyte-activation gene 3 (LAG-3) blocking antibody. LAG-3 functions to control T-cell response, activation and growth. Nivolumab is a programmed death-1 (PD-1) immune checkpoint inhibitor designed to help restore anti-tumor immune response.
The application is supported by data from the phase 2/3 RELATIVITY-047 trial (ClinicalTrials.gov Identifier: NCT03470922), which assessed the efficacy and safety of relatlimab plus nivolumab in 714 patients with previously untreated metastatic or unresectable melanoma. Patients were randomly assigned 1:1 to receive either a fixed-dose combination of relatlimab 160mg plus nivolumab 480mg by intravenous infusion every 4 weeks or nivolumab 480mg by intravenous infusion every 4 weeks until disease recurrence, unacceptable toxicity or withdrawal of consent.
The primary endpoint was progression-free survival (PFS), as assessed by blinded independent central review using RECIST v1.1.
Results showed a median PFS of 10.12 months (95% CI, 6.37-15.74) for the fixed-dose combination therapy compared with 4.63 months (95% CI, 3.38-5.62) for nivolumab alone (hazard ratio, 0.75; 95% CI, 0.62-0.92; P =.0055). At 12 months, the PFS rates were 47.7% (95% CI, 41.8-53.2) for the fixed-dose combination and 36% (95% CI, 30.5-41.6) for nivolumab alone. No new safety signals or new types of clinically important events were observed with the combination therapy when compared to nivolumab monotherapy.
A Prescription Drug User Fee Act (PDUFA) target date of March 19, 2022 has been set for the application.
- 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. https://news.bms.com/news/details/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.
- Lipson EJ, Tawbi HA, Schadendorf D, et al. Relatlimab (RELA) plus nivolumab (NIVO) versus NIVO in first-line advanced melanoma: primary phase III results from RELATIVITY-046 (CA224-047). J Clin Oncol. 2021;39(suppl 15):9503. doi:10.1200/JCO.2021.39.15_suppl.9503
- Bristol Myers Squibb announces LAG-3-blocking antibody relatlimab and nivolumab fixed-dose combination significantly improves progression-free survival vs. Opdivo (nivolumab) in patients with previously untreated metastatic or unresectable melanoma. News release. Bristol Myers Squibb. May 19, 2021. https://news.bms.com/news/corporate-financial/2021/Bristol-Myers-Squibb-Announces-LAG-3-Blocking-Antibody-Relatlimab-and-Nivolumab-Fixed-Dose-Combination-Significantly-Improves-Progression-Free-Survival-vs.-Opdivo-nivolumab-in-Patients-with-Previously-Untreated-Metastatic-or-Unresectable-Melanoma/default.aspx.