Fixed dose combination of nivolumab and relatlimab improved progression free survival

A trial investigating programmed death-1 (PD-1) inhibitor nivolumab in combination with relatlimab, an anti-LAG-3 antibody, has met the primary endpoint of progression free-survival (PFS).  

In the Phase II/III RELATIVITY-047 trial, a total of 714 patients with previously untreated metastatic or unresectable melanoma were randomised 1:1 to receive a fixed dose combination of relatlimab 160 mg and nivolumab 480 mg or nivolumab 480 mg by intravenous infusion every four weeks.

Although the actual PFS figures were not disclosed in the top-line results, researchers reported that the fixed-dosed combination of nivolumab plus relatlimab demonstrated benefit for patients with previously untreated metastatic or unresectable melanoma.

The follow-up for overall survival – a secondary endpoint of the trial – is still ongoing.  

Relatlimab is designed to block the lymphocyte-activation gene 3 (LAG-3), a cell-surface molecule expressed on effector T cells and regulatory T cells (Tregs). 

This molecule functions to control T cell response, activation and growth, with preclinical studies indicating that inhibition of the LAG-3 pathway may restore effector function of exhausted T cells. 

Researchers believe that this could potentially promote an anti-tumour response – early research has demonstrated that targeting the LAG-3 pathway in combination with other immune checkpoint pathways, such as PD-1, could ‘more effectively’ increase the power of anti-tumour immune activity. 

“The results of this study suggest that targeting the LAG-3 pathway in combination with PD-1 inhibition may be a key strategy to enhance the immune response and help improve outcomes for these patients,” said Jonathan Cheng, senior vice president and head of oncology development, Bristol Myers Squibb (BMS).

In addition to melanoma, BMS is evaluating relatlimab in clinical trials in combination with other agents across a number of tumour types.