FDA Approves Opdualag™ (Nivolumab and Relatlimab-rmbw): First PD-1/LAG-3 Dual Immune Checkpoint Inhibitor for First-Line Treatment of Unresectable or Metastatic Melanoma

News on March 20, 2022 /BioValleyBIOON/ --Bristol-Myers Squibb (BMS) recently announced that the U.S. Food and Drug Administration (FDA) has approved Opdualag (nivolumab and relatlimab-rmbw), administered as a single intravenous infusion, for the treatment of unresectable or metastatic disease in patients aged 12 years and older.MelanomaAdult patients and pediatric patients.

Opdualag is the first LAG-3 blocking antibody combination product to receive regulatory approval., is a first-of-its-kind, fixed-dose, dual immunotherapy product composed of the PD-1 inhibitor nivolumab (Opdivo) and the novel LAG-3 blocking antibody relatlimab. In the Phase 2/3 RELATIVITY-047 (CA224-047) trial, Opdualag more than doubled progression-free survival (PFS) compared to the standard-of-care therapy Opdivo (nivolumab).

Relatlimab is the third unique checkpoint inhibitor (anti-PD-1, anti-CTLA-4, anti-LAG-3) being evaluated by Bristol-Myers Squibb, further expanding the company's growing and differentiated portfolio.TumorThe academic product portfolio has been infused with new vitality.

This approval is based on the results of the Phase 2/3 RELATIVITY-047 (CA224-047) trial, a randomized, double-blind Phase 2/3 study in patients with metastatic or unresectable disease who had not received prior treatment.MelanomaConducted in patients, evaluating the efficacy and safety of Opdualag (relatlimab 160mg and nivolumab 400mg, intravenous infusion once every 4 weeks) and standard-of-care Opdivo (nivolumab, 480mg, intravenous infusion once every 4 weeks) as monotherapy for first-line treatment.

The results showed that the trial met the primary endpoint:Compared with standard-of-care Opdivo monotherapy, first-line treatment with Opdualag demonstrated strong efficacy, more than doubling progression-free survival (PFS) (median PFS: 10.1 months vs 4.6 months) and reducing the risk of disease progression or death by 25% (HR=0.75, 95% CI: 0.62-0.92; p=0.0055), with statistically significant and clinically meaningful data.

The PFS benefit of Opdualag was observed as early as the first scan and showed consistency over time. In exploratory, descriptive analyses, Opdualag extended PFS regardless of prespecified subgroups and stratification factors.

In the trial, the safety of Opdualag was similar to the previously reported safety profile of Opdivo. No new safety events were identified with the combination therapy compared to Opdivo monotherapy. The incidence of grade 3/4 drug-related adverse events was 18.9% in the Opdualag group and 9.7% in the Opdivo group. The incidence of drug-related adverse events leading to discontinuation was 14.6% in the Opdualag group and 6.7% in the Opdivo group.

Relatlimab Mechanism of Action (Click image to enlarge)

Lymphocyte activation gene 3 (LAG-3, CD223) is a cell surface molecule expressed on effector T cells and regulatory T cells (Tregs). LAG-3 regulates an inhibitory immune checkpoint pathway, limiting T cell activity, leading to reduced attack.TumorThe ability of cells is impaired. In chronic diseases such as cancer, T cells exhibit progressive exhaustion, characterized by the upregulation of inhibitory immune checkpoints such as PD-1 and LAG-3. Although LAG-3 and PD-1 are distinct immune checkpoint pathways, they may synergistically act on effector T cells, leading to T cell exhaustion.

Immune checkpoint inhibitors, used alone or in combination, have transformed the treatment landscape for metastatic or unresectable diseases.MelanomaThe treatment method for patients has improved survival rates. However, a significant number of patients may still benefit from a new combination therapy that utilizes potentially complementary pathways to enhance anti-TumorActivity. The results of the RELATIVITY-047 study indicate that targeting the LAG-3 pathway in combination with PD-1 inhibition may be a key strategy to enhance immune response and help improve outcomes for these patients.

LAG-3 represents a new immunotherapy target, and the RELATIVITY-047 study confirmed the significant benefits of using the novel combination regimen of relativimab and nivolumab (Opdualag) to simultaneously inhibit LAG-3 and PD-1. Based on the observed efficacy and safety, Opdualag will provide a new treatment option for metastaticMelanomaPatients are provided with an important new treatment option. (Bioon.com)

Source of the original text: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