In the Clinic provides overviews of novel oncology agents, addressing indications, mechanisms of action, administration recommendations, safety profiles, and other essential information needed for the appropriate clinical use of these drugs.
On March 18, 2022, fixed-dose nivolumab and relatlimab-rmbw was approved for treatment of adult and pediatric patients aged 12 years and older with unresectable stage III or metastatic melanoma.1 This medication is a fixed-dose combination of the lymphocyte activation gene-3 (LAG-3)-blocking antibody relatlimab-rmbw and nivolumab.
Supporting Efficacy Data
Approval was based on findings in the phase III double-blind RELATIVITY-047 trial (ClinicalTrials.gov identifier NCT03470922). In this study, 714 patients were randomly assigned to receive the combination (nivolumab at 480 mg and relatlimab at 160 mg) every 4 weeks (n = 355) or nivolumab at 480 mg every 4 weeks (n = 359) until disease progression or unacceptable toxicity. Exclusion criteria included uveal melanoma and active or untreated brain or leptomeningeal metastases.
Median progression-free survival on blinded independent central review, the major efficacy outcome measure, was 10.1 months (95% confidence interval [CI] = 6.4–15.7 months) in the nivolumab/relatlimab group vs 4.6 months (95% CI = 3.4–5.6 months) in the nivolumab group (hazard ratio [HR] = 0.75, 95% CI = 0.62–0.92, P = .0055). The final overall survival analysis did not show a significant benefit with nivolumab/relatlimab (median = not reached, 95% CI = 34.2 months to not reached, vs 34.1 months, 95% CI = 25.2 months to not reached: HR = 0.80, 95% CI = 0.64–1.01).
How It Is Used
The recommended nivolumab/relatlimab dose for adult and pediatric patients aged 12 and older who weigh at least 40 kg is 480 mg of nivolumab and 160 mg of relatlimab every 4 weeks until disease progression or unacceptable toxicity. The recommended dose for pediatric patients who weigh less than 40 kg has not been established.
No dose reductions of nivolumab/relatlimab are recommended. Product labeling provides instructions for dosage modification for immune-mediated adverse reactions and infusion-related reactions.
In RELATIVITY-047, the most common adverse events of any grade in the nivolumab/relatlimab group were musculoskeletal pain (45% vs 31% in the nivolumab group), fatigue (39% vs 29%), rash (28% vs 21%), pruritus (25% vs 17%), and diarrhea (24% vs 17%). The most common grade 3 or 4 adverse events included musculoskeletal pain (4.2%) and rash (1.4%). The most common grade 3 or 4 laboratory abnormalities were increased alanine aminotransferase (3.2%) and decreased hemoglobin (2.7%).
Serious adverse events occurred in 36% of patients in the nivolumab/relatlimab group, most commonly adrenal insufficiency, anemia, colitis, and pneumonia (1.4% each). Adverse events led to treatment discontinuation in 18%, most commonly myocarditis (1.7%) and pneumonitis (1.4%). Fatal adverse events occurred in three patients (0.8%), consisting of hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
Nivolumab/relatlimab has warnings/precautions for immune-mediated adverse reactions (including pneumonitis, colitis, hepatitis, endocrinopathies, dermatologic reactions, nephritis with renal dysfunction, and myocarditis); infusion-related reactions; complications of allogeneic hematopoietic stem cell transplantation; and embryofetal toxicity. Patients should be advised not to breastfeed while receiving nivolumab/relatlimab.
1. Opdualag (nivolumab and relatlimab-rmbw) injection, for intravenous use, prescribing information, Bristol Myers Squibb Company, March 2022. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761234s000lbl.pdf. Accessed March 31, 2022.