Efficacy and safety of first-line (1L) nivolumab plus relatlimab (NIVO + RELA) versus NIVO plus ipilimumab (NIVO + IPI) in advanced melanoma: An updated indirect treatment comparison (ITC).

9557 Background: An ITC comparing NIVO + RELA and NIVO + IPI, approved dual immunotherapy treatment options for patients with advanced melanoma, was previously conducted using pt-level data from the pivotal RELATIVITY-047 (RELA-047; NIVO + RELA vs NIVO) and CheckMate 067 (CM-067; NIVO + IPI or NIVO vs IPI) trials (Schadendorf 2023). Here we present results using updated, 3-year follow-up data from RELA-047. Methods: Inverse probability of treatment weighting was used to adjust for cross-trial imbalances in baseline characteristics. Database locks were selected to best align follow-up length in RELA-047 (median 34 mo) and CM-067 (median 38 mo). Progression-free survival (PFS) per investigator, confirmed objective response rates (ORRs) per investigator, overall survival (OS), melanoma-specific survival (MSS), treatment-related adverse events (TRAEs), and TRAEs leading to discontinuation (DC) were analyzed. PFS, OS, and ORR were evaluated across key subgroups. PFS, OS, and MSS were compared using Kaplan–Meier curves and hazard ratios (HRs); ORRs were compared using odds ratios (ORs). The weighted NIVO arm from each trial was compared for internal validation. Results: After weighting, key baseline characteristics were balanced for NIVO + RELA (n=339) and NIVO + IPI (n=297). Efficacy outcomes after weighting were similar between NIVO + RELA and NIVO + IPI and between NIVO arms (table). Similar outcomes between the NIVO arms validate the ITC methodology. Across subgroups, efficacy appeared similar between treatments, although trends favoring NIVO + IPI were observed for ORR among pts with BRAF MT disease or lactate dehydrogenase > 2x the upper limit of normal. TRAEs were less common with NIVO + RELA (23%) compared to NIVO + IPI (61%); any-grade TRAEs leading to DC occurred in 17% and 41% of pts, respectively. Conclusions: Consistent with previous results, this updated ITC suggests that 1L treatment with NIVO + RELA may have comparable efficacy to, and lower toxicity than, NIVO + IPI in pts with advanced melanoma. Results should be interpreted with caution given differences in study designs and changes in treatment landscape. Research is ongoing to determine which pts respond best with each combination. Table: see text