RELATIVITY-048

Based on the results of CheckMate-067 and RELATIVITY-047, the combination of nivolumab with either ipilimumab or relatlimab (anti LAG-3) gained approval as first line treatment options for patients with advanced melanoma. The findings of these trials also formed the rationale for part 2B of the phase I/II RELATIVITY-048 study, in which the triplet combination of nivolumab, ipilimumab and relatlimab was evaluated in previously untreated advanced melanoma patients. During ASCO 2024, Prof Dr Paolo Ascierto (Istituto Nazionale Tumori – Fondazione G. Pascale, Naples, Italy) discussed the safety and efficacy results of this trial.

In total 46 patients with previously untreated advanced melanoma were treated with a combination of nivolumab (480 mg q4w), relatlimab (160 mg q4w) and ipilimumab (1 mg/kg q8w). The median age of these patients was 61 years, 50% had a BRAF-mutation, 20% had a baseline lactate dehydrogenase level of more than twice the upper limit of normal and 30% presented with liver metastases at study entry.

The objective response rate (per investigator) was reported at 59%, with 17% of patients obtaining a complete response. With an additional 17% of patients experiencing disease stabilization, the clinical benefit rate with the triplet combination mounted to 76%. At the 4-year landmark, the rate of progression-free (PFS) and overall survival (OS) was impressive at 52% and 72%, respectively. Importantly, these rates exceed the 4-year PFS, and OS rates reported in CheckMate-067 and RELATIVITY-047 by approximately 20%.

The investigators did not encounter any new safety signals with the triplet regimen compared to other immunotherapy combinations. All grade and grade ≥3 treatment related adverse events (TRAEs) were observed in 96% and 39% of patients, respectively. Overall, 41% of patients discontinued the treatment due to a TRAE.

Prof Ascierto concluded that the efficacy findings in this study are very promising and warrant further evaluation in a larger, randomized-controlled trial. Furthermore, the safety profile of this triplet regimen seems to be comparable to that of established dual immunotherapy combinations.