RELATIVITY-048: Triplet Immunotherapy Shows Activity in Untreated Advanced Melanoma
Source: The Asco Post, July 2024
As a first-line treatment of advanced melanoma, the triplet immunotherapy regimen of nivolumab, relatlimab-rmbw, and ipilimumab produced high response rates and promising progression-free and overall survival in the nonrandomized phase I/II RELATIVITY-048 trial, as reported by Paolo Antonio Ascierto, MD, of the Istituto Nazionale dei Tumori IRCCS in Naples, Italy, at the 2024 ASCO Annual Meeting.
“Preliminary efficacy data from 46 patients compare favorably with historical published data from nivolumab plus ipilimumab2 and nivolumab plus relatlimab,3 though cross-trial comparisons should be interpreted with caution,” Dr. Ascierto said. He cited the overall survival rate in RELATIVITY-048 (an exploratory endpoint) as 72% at 4 years, compared with approximately 20% with the doublets.
Background for the Triplet
Lymphocyte-activation gene 3 (LAG3) and PD-1 are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG3-blocking antibody, and nivolumab, a PD-1–blocking antibody, previously showed benefit in RELATIVITY-047. In an updated 2-year analysis presented at the 2023 ASCO Annual Meeting, median progression-free survival was 10.2 months with the doublet vs 4.6 months with nivolumab alone (hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.67–0.97).3 Median overall survival was not reached and was 33.2 months with nivolumab alone (HR = 0.82; 95% CI = 0.67–1.02). At 4 years 52% and 42% of the respective cohorts were alive. However, the study was not powered for an overall survival difference.