BMS’ Opdivo plus LAG-3 antibody relatlimab show promise in melanoma

Bristol Myers Squibb (BMS) has revealed top-line data from a Phase II/III trial evaluating its PD-1 inhibitor Opdivo plus its investigational anti-LAG-3 antibody relatlimab in previously untreated metastatic or unresectable melanoma.

The RELATIVITY-047 trial is evaluating a fixed-dose combination of Opdivo (nivolumab) and relatlimab compared to Opdivo alone in these patients.

According to BMS, the trial met its primary endpoint of progression-free survival, with follow-up for the secondary endpoint of overall survival still ongoing.

Although the company did not disclose the actual figures for the combination treatment, BMS said it would present the results at an upcoming meeting and discuss the findings with regulatory authorities.

Lymphocyte-activation gene 3 (LAG-3) is expressed on effector T cells and regulatory T cells (Tregs). It regulates an inhibitory immune checkpoint pathway that limits the activity of T cells, which is believed to cause an impaired ability to attack tumour cells.

In cancer, T cells exhibit progressive exhaustion that is characterised by the upregulation of inhibitory immune checkpoints, including PD-1 and LAG-3.

Although PD-1 and LAG-3 are distinct immune checkpoint pathways, they could potentially act ‘synergistically’ on effector T cells leading to T cell exhaustion, BMS said in a statement.

“Immune checkpoint inhibitors alone or in combination have transformed treatment and improved survival rates for patients with metastatic or unresectable melanoma,” said Jonathan Cheng, senior vice president and head of oncology development, BMS.

He added: “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.”