On March 18, 2022, the Food and Drug Administration approved nivolumab and relatlimab-rmbw for adult and paediatric patients 12 years of age or older with unresectable or metastatic melanoma. Nivolumab and relatlimab-rmbw is a fixed-dose combination of the LAG-3-blocking antibody relatlimab and the programmed death receptor-1 blocking antibody nivolumab.

Efficacy was evaluated in RELATIVITY-047 (NCT03470922), a randomized (1:1), double-blinded trial in 714 patients with previously untreated metastatic or unresectable Stage III or IV melanoma.

The 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. Patients were randomized to receive nivolumab and relatlimab-rmbw (nivolumab 480 mg and relatlimab 160 mg) by intravenous infusion every 4 weeks or nivolumab 480 mg by intravenous infusion every 4 weeks until disease progression or unacceptable toxicity.

The major efficacy outcome measure was progression-free survival (PFS) determined by Blinded Independent Central Review (BICR) using RECIST v1.1.

The trial demonstrated a statistically significant improvement in PFS by BICR for nivolumab and relatlimab-rmbw compared to nivolumab (HR=0.75; 95% confidence interval [CI]: 0.62, 0.92; p-value=0.0055). Median PFS was 10.1 months (95% CI: 6.4, 15.7) in the nivolumab and relatlimab-rmbw arm and 4.6 months (95% CI: 3.4, 5.6) in the nivolumab arm.

An additional efficacy outcome measure was overall survival (OS). The final analysis of OS was not statistically significant (HR=0.80; 95% CI: 0.64, 1.01) with median OS not reached (NR) in the nivolumab and relatlimab-rmbw arm (95% CI: 34.2, NR) and 34.1 months (95% CI: 25.2, NR) in the nivolumab arm.

The most common adverse reactions (≥20%) of nivolumab and relatlimab-rmbw, were musculoskeletal pain, fatigue, rash, pruritus, and diarrhoea. The most common laboratory abnormalities (≥20%) were decreased haemoglobin, decreased lymphocytes, increased AST, increased ALT, and decreased sodium.

The recommended nivolumab and relatlimab-rmbw dose for adult and paediatric 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 dose for paediatric patients 12 years of age or older who weigh less than 40 kg has not been established.

View full prescribing information for nivolumab and relatlimab-rmbw here.

Source: FDA