Relatlimab-nivolumab combination effective in metastatic melanoma

21st January 2022

Relatlimab-nivolumab in combination led to an increase in progression-free survival in metastatic melanoma compared to nivolumab alone

The combination of relatlimab-nivolumab has been shown to improve progression-free survival to a greater extent that nivolumab alone in patients with metastatic or unresectable melanoma, compared to nivolumab alone. This was the conclusion of a Phase II-III trial by researchers from the Department of Melanoma Medical Oncology, University of Texas, US.

The prognosis for patients with advanced melanoma is poor, with 5-years survival rates of 5-19%, depending on the location and the number of metastases. Nevertheless, over the past decade, there have been improvements in survival for such patients, after the introduction of drugs such as ipilimumab (an anti–cytotoxic T-lymphocyte–associated antigen 4 monoclonal antibody) and anti–programmed death 1 agents such as nivolumab.

In fact, studies suggest that the combination of ipilimumab and nivolumab, can produce a median overall survival of more than 60.0 months, compared to 36.9 months with nivolumab and 19.9 months ipilimumab mono-therapy respectively.

Lymphocyte Activation Gene – 3 (LAG-3) is an immune checkpoint molecule that regulates both T-cell activation and homeostasis and is up-regulated in melanoma. In addition, it has been found that both LAG-3 and programmed cell death 1 (PD-1) act synergistically to regulate T-cell function to promote tumour immune escape.

Consequently, the use of relatlimab (an antibody that binds to LAG-3) and nivolumab (a PD-1 inhibitor), has showed promising anti-tumour activity, including a durable objective responses in patients with melanoma that relapsed after, or was found to be refractory to PD-1 inhibition.

For the present study, the US team used relatlimab-nivolumab as a fixed-dose combination, compared to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. They included patients 12 years of age and older, with previously untreated, histologically confirmed, unresectable stage III or IV melanoma.

In phase 2–3, double-blind trial, included patients were randomised 1:1 to 160 mg of relatlimab and 480 mg of nivolumab or 480 mg of nivolumab, with both therapies administered in a single 60-minute intravenous infusion every 4 weeks. The primary end point of the study was progression-free survival assessed according to RECIST, version 1.1.

Findings

A total of 714 patients with a mean age of 63 years (41.7% female) were randomised to either relatlimab-nivolumab (355) or nivolumab alone.

The median progression-free survival interval was 10.1 months with relatlimab–nivolumab and 4.6 months with nivolumab, giving a hazard ratio (HR) for progression or death of 0.75 (95% CI 0.62 – 0.92, p = 0.006). After 12 months, progression-free survival was 47.7% with relatlimab–nivolumab and 36% with nivolumab.

The authors concluded that their data support the role of dual checkpoint inhibition over mono-therapy and establish relatlimab–nivolumab as a potential new treatment option for patients with previously untreated metastatic or unresectable melanoma.

Citation

Tawbi HA et al. Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. New Eng J Med 2022