FDA Approves Bristol Myers’ Opdualag for Unresectable or Metastatic Melanoma
American multinational pharmaceutical company Bristol Myers Squibb has announced that OpdualagTM , a new, first-in-class, fixed-dose combination of nivolumab and relatlimab, administered as one intravenous infusion, was approved by the FDA for the treatment of patients 12 years of age or older with unresectable or metastatic melanoma. The approval is based on the Phase 2/3 RELATIVITY-047 trial, which compared Opdualag (n=355) to nivolumab alone (n=359).
The First LAG-3-Blocking Antibody Combination, Opdualag™ (nivolumab and relatlimab-rmbw) approved by the FDA
The Phase 2/3 RELATIVITY-047 trial met its primary endpoint, progression-free survival (PFS), and Opdualag more than doubled the median PFS when compared to nivolumab monotherapy, 10.1 months (95% Confidence Interval [CI]: 6.4 to 15.7) versus 4.6 months (95% CI: 3.4 to 5.6); (Hazard Ratio [HR] 0.75; 95% CI: 0.62 to 0.92, P=0.0055). The Opdualag safety profile was comparable to that previously reported for nivolumab. No new safety events were identified with the combination when compared to nivolumab monotherapy. Grade 3/4 drug-related adverse events were 18.9% in the Opdualag arm compared to 9.7% in the nivolumab arm. Drug-related adverse events leading to discontinuation were 14.6% in the Opdualag arm compared to 6.7% in the nivolumab arm.
F. Stephen Hodi, M.D., director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber Cancer Institute stated:
“Since the approval of the first immune checkpoint inhibitor more than 10 years ago, we’ve seen immunotherapy, alone and in combination, revolutionize the treatment of patients with advanced melanoma. Today’s approval is particularly significant, as it introduces an entirely new combination of two immunotherapies that may act together to help improve anti-tumor response by targeting two different immune checkpoints — LAG-3 and PD-1.”
Samit Hirawat, chief medical officer, global drug development, Bristol Myers Squibb said:
“While we have made great progress in the treatment of advanced melanoma over the past decade, we are committed to expanding dual immunotherapy treatment options for these patients. Inhibiting LAG-3 with relatlimab, in a fixed-dose combination with nivolumab, represents a new treatment approach that builds on our legacy of bringing innovative immunotherapy options to patients. The approval of a new medicine that includes our third distinct checkpoint inhibitor marks an important step forward in giving patients more options beyond monotherapy treatment.”
Lymphocyte activation gene-3 (LAG-3) and programmed death-1 (PD-1) are two distinct inhibitory immune checkpoints that are often co-expressed on tumor-infiltrating lymphocytes, thus contributing to tumor-mediated T-cell exhaustion. The combination of nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) results in increased T-cell activation compared to the activity of either antibody alone. Relatlimab (in combination with nivolumab) is the first LAG-3-blocking antibody to demonstrate a benefit in a Phase 3 study. For Bristol Myers Squibb It is the third checkpoint inhibitor, along with anti-PD-1 and anti-CTLA-4.
Michael Kaplan, president and CEO, Melanoma Research Alliance commented:
“Today’s approval is exciting news and offers new hope to the melanoma community. The availability of this treatment combination may enable patients to potentially benefit from a new, first-in-class dual immunotherapy.”
About the RELATIVITY-047 Trial
RELATIVITY-047 is a global, randomized, double-blind Phase 2/3 study evaluating the fixed-dose combination of nivolumab and relatlimab versus nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. The clinical trial excluded patients with active autoimmune disease, medical conditions requiring systemic treatment with moderate or high dose corticosteroids or immunosuppressive medications, uveal melanoma, and active or untreated brain or leptomeningeal metastases. The primary endpoint of the trial is progression-free survival (PFS) determined by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumors (RECIST v1.1). The secondary endpoints are overall survival (OS) and objective response rate (ORR). A total of 714 patients were randomized 1:1 to receive a fixed-dose combination of nivolumab (480 mg) and relatlimab (160 mg) or nivolumab (480 mg) by intravenous infusion every four weeks until disease progression or unacceptable toxicity.
Melanoma is a form of skin cancer characterized by the uncontrolled growth of pigment-producing cells (melanocytes) located in the skin. Metastatic melanoma is the deadliest form of the disease and occurs when cancer spreads beyond the surface of the skin to other organs. The incidence of melanoma has been increasing steadily for the last 30 years. In the US, approximately 99,780 new diagnoses of melanoma and about 7,650 related deaths are estimated for 2022. Melanoma can be mostly treatable when caught in its very early stages; however, survival rates can decrease as the disease progresses.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, please visit us at BMS.com
Celgene and Juno Therapeutics are wholly owned subsidiaries of Bristol-Myers Squibb Company. In certain countries outside the U.S., due to local laws, Celgene and Juno Therapeutics are referred to as, Celgene, a Bristol Myers Squibb company and Juno Therapeutics, a Bristol Myers Squibb company.
Original Press Release – Published 03/18/2022 : https://news.bms.com/news/details/2022/U.S.-Food-and-Drug-Administration-Approves-First-LAG-3-Blocking-Antibody-Combination-Opdualag-nivolumab-and-relatlimab-rmbw-as-Treatment-for-Patients-with-Unresectable-or-Metastatic-Melanoma/default.aspx