NEWS

PIONEERING INTERNATIONAL STUDY ON THE TREATMENT OF METASTATIC MELANOMA WITH THE PARTICIPATION OF MRS. HELEN GOGAS, PROFESSOR OF THE NATIONAL AND KAPODISTRIAN UNIVERSITY OF ATHENS

Pioneering international study on the treatment of metastatic melanoma with the participation of Mrs. Helen Gogas, Professor of the National and Kapodistrian University of Athens

New checkpoint inhibitor shows efficacy in metastatic melanoma

Following the durable remissions in metastatic melanoma patients induced by PD-1/PD-L1 inhibitors, many combinatorial approaches with additional immunotherapeutic agents have been recently tested to overcome T-cell exhaustion and further enhance immunological response. Activated or chronically stimulated T cells upregulate various co-inhibitory molecules, such as programmed cell death protein 1 (PD-1), and lymphocyte activation gene 3 (LAG-3, CD223), contributing to tumor-mediated T-cell exhaustion. Relatlimab is a first-in-class human IgG4 LAG-3–blocking antibody that binds to LAG-3 and restores the effector function of exhausted T cells. In preclinical models, dual inhibition of LAG-3 and PD-1 showed synergistic antitumor activity.

In a phase 1–2 dose-escalation and cohort-expansion trial, the combination of relatlimab and nivolumab, a PD-1 inhibitor, showed antitumor activity, including durable responses and good tolerance in patients with melanoma that relapsed after, or was refractory to, PD-1 inhibition. In January 2022, the RELATIVITY-047 study, a phase 2–3, global, double-blind, randomized trial [NCT03470922], published its results from the LAG-3 and PD-1 co-inhibition with relatlimab–nivolumab as a new fixed-dose combination in comparison with nivolumab alone in patients with previously untreated metastatic or unresectable melanoma.

The primary end point was progression-free survival (PFS) as assessed by blinded independent central review. After a median follow-up of 13.2 months, the median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab–nivolumab as compared with 4.6 months (95%CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P = 0.006 by the log-rank test). At 12 months PFS% was 47.7% (95% CI, 41.8 to 53.2) with relatlimab–nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Across key subgroups, PFS favored relatlimab–nivolumab over nivolumab. Grade 3 or 4 TRAES occurred in 18.9% of patients in the relatlimab-nivolumab group and in 9.7% of patients in the nivolumab group.

The authors concluded that the inhibition of both immune checkpoints, LAG-3 and PD-1, provided a greater benefit with regard to PFS than anti-PD-1 monotherapy in patients with previously untreated metastatic or unresectable melanoma, without adding any new safety signals.

Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma