Opdualag, a Novel Immunotherapy Combination, FDA Approved for Advanced Melanoma

Web Exclusives - FDA Approvals

On March 18, 2022, the FDA approved the combination of 2 types of immune checkpoint inhibitors, the PD-1 inhibitor nivolumab (Opdivo; Bristol Myers Squibb) plus the novel LAG-3 inhibitor relatlimab-rmbw (Opdualag; Bristol Myers Squibb), for patients aged ≥12 years with unresectable or metastatic melanoma. Opdualag is a new fixed-dose combination of the 2 monoclonal antibodies, relatlimab-rmbw and nivolumab.

The FDA approved this new combination therapy based on results of the RELATIVITY-047 clinical trial, a randomized (1:1) double-blind study of 714 patients with newly diagnosed metastatic or unresectable stage III or IV melanoma. The study excluded patients with active autoimmune disease requiring systemic therapy with moderate- or high-dose corticosteroids or immunosuppressive medications, uveal melanoma, or active or untreated brain or leptomeningeal metastases.

Patients were randomized to the combination of intravenous (IV) nivolumab 480 mg plus IV relatlimab 160 mg or to IV nivolumab 480 mg, alone, either infused every 4 weeks until disease progression or until unacceptable toxicity. The key efficacy outcome was progression-free survival (PFS) using RECIST version 1.1.

The results showed a significant PFS improvement favoring relatlimab plus nivolumab versus nivolumab alone (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.62-0.92; P = .0055). The median PFS was 10.1 months (95% CI, 6.4-15.7) with relatlimab plus nivolumab versus 4.6 months (95% CI, 3.4-5.6) with nivolumab alone. The overall survival (OS) was not significantly different between the 2 arms (HR, 0.80; 95% CI, 0.64-1.01), and the median OS was not reached (NR) in the relatlimab plus nivolumab arm (95% CI, 34.2-NR) and was 34.1 months (95% CI, 25.2-NR) in the nivolumab-alone arm.

“As the data from the RELATIVITY-047 trial mature, if the survival benefit of relatlimab–nivolumab is shown to be similar to or better than that of nivolumab–ipilimumab, this finding would reinforce the relatlimab–nivolumab regimen as the new standard of care for previously untreated patients with advanced melanoma,” Dr Frampton and Dr Sivakumar wrote in an editorial in the New England Journal of Medicine.1

The most common (≥20%) adverse reactions seen with this monoclonal antibodies combination were musculoskeletal pain, fatigue, rash, pruritus, and diarrhea. The most common (≥20%) laboratory abnormalities were decreased hemoglobin levels, decreased lymphocytes, increased aspartate aminotransferase, increased alanine aminotransferase, and decreased sodium.

The recommended dose of relatlimab plus nivolumab for patients aged ≥12 years weighing ≥40 kg is IV nivolumab 480 mg and IV relatlimab 160 mg every 4 weeks until disease progression or unacceptable toxicity occurs. The recommended dose for patients aged ≤12 years weighing <40 kg has not been established.

  1. Frampton AE, Sivakumar S. A new combination immunotherapy in advanced melanoma. N Engl J Med. 2022;386:91-92.
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Last modified: May 3, 2022
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