General Information

Opdualag is a combination of nivolumab, a programmed death receptor-1 (PD-1) blocking antibody, and relatlimab, a lymphocyte activation gene-3 (LAG-3) blocking antibody.

Opdualag is specifically indicated for the treatment of adult and pediatric patients 12 years of age or older with unresectable or metastatic melanoma.

Opdualag is supplied as an injection for intravenous administration. The recommended dosage of Opdualag for adult patients and pediatric patients 12 years of age or older who weigh at least 40 kg is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks until disease progression or unacceptable toxicity occurs. The recommended dosage for pediatric patients 12 years of age or older who weigh less than 40 kg has not been established.

Mechanism of Action

Relatlimab is a human IgG4 monoclonal antibody that binds to the LAG-3 receptor, blocks interaction with its ligands, including MHC II, and reduces LAG-3 pathway mediated inhibition of the immune response. Antagonism of this pathway promotes T cell proliferation and cytokine secretion. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T-cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors, and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.

Nivolumab is a human IgG4 monoclonal antibody that binds to the PD-1 receptor, blocks interaction with its ligands PD-L1 and PD-L2, and reduces PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

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. In murine syngeneic tumor models, LAG-3 blockade potentiates the anti-tumor activity of PD-1 blockage, inhibiting tumor growth and promoting tumor regression.

Side Effects

Adverse effects associated with the use of Opdualag may include, but are not limited to, the following:

• musculoskeletal pain
• fatigue
• rash
• pruritus
• diarrhea
• laboratory abnormalities, including decreased hemoglobin, decreased lymphocytes, increased AST, increased ALT, and decreased sodium

Clinical Trial Results

FDA approval was based on the Phase 2/3 RELATIVITY-047 trial which compared Opdualag (n=355) to nivolumab alone (n=359). The trial met its primary endpoint, progression-free survival (PFS). Opdualag more than doubled the median PFS when compared to nivolumab monotherapy: 10.1 months versus 4.6 months.