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) with 4-year follow-up data.

9554 Background: An ITC comparing NIVO + RELA and NIVO + IPI, approved dual immunotherapy treatment options for patients (pts) 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 (Long JCO 2024). Here we present updated results using 4-year follow-up data from RELA-047. Methods: Inverse probability of treatment weighting was used to adjust for cross-trial imbalances in baseline characteristics. CM-067 follow-up was truncated (median 41.0 mo) to best align with the follow-up length in RELA-047 (median 34.9 mo). Progression-free survival (PFS) per investigator, confirmed objective response rates (ORRs) per investigator, overall survival (OS), and melanoma-specific survival (MSS) were analyzed. Outcomes were also evaluated across key subgroups. The weighted NIVO arms from each trial were compared for internal validation. Results: After weighting, key baseline characteristics were balanced for NIVO + RELA (n=339) and NIVO + IPI (n=297). Outcomes after weighting were similar between NIVO + RELA and NIVO + IPI (hazard ratio [HR] [95% CI]: PFS 1.08 [0.89–1.33]; OS 0.95 [0.76–1.19]; table). Outcomes were similar between the NIVO arms, validating the ITC methodology. Across subgroups, efficacy appeared similar between treatments, although trends favoring NIVO + IPI were observed for ORR among pts with BRAF-mutant disease or serum lactate dehydrogenase >2x the upper limit of normal. Results when NIVO + IPI follow-up was untruncated were consistent with the truncated analyses. Conclusions: Consistent with previous results, this updated ITC with longer follow-up from RELA-047 suggests that 1L treatment with NIVO + RELA may have comparable efficacy to NIVO + IPI in pts with advanced melanoma, including most—but not all—subgroups. Results should be interpreted with caution given differences in study design and changes in the treatment landscape over time. Efficacy outcomes after weighting. NIVO + RELA (n = 339) NIVO + IPI (n = 297) HR/odds ratio [OR] (95% CI) NIVO RELA-047 (n = 338) NIVO CM-067 (n = 288) HR/OR (95% CI) Median PFS per INV, mo (95% CI) 12.0 (8.2–17.1) 11.2 (8.5–18.1) 1.08 (0.89–1.33) 6.6 (4.6–10.1) 5.7 (3.9–9.1) 0.96 (0.79–1.16) Confirmed ORR per INV, % 48 50 0.91 (0.73–1.14) 40 40 1.00 (0.79–1.28) Median OS, mo (95% CI) 64.5 (38.6–NR) NR (37.1–NR) 0.95 (0.76–1.19) 35.1 (27.3–48.8) 35.7 (26.4–NR) 1.02 (0.83–1.26) Median MSS, mo (95% CI) NR (NR–NR) NR (NR–NR) 0.87 (0.68–1.12) 51.2 (34.7–NR) 44.8 (32.3–NR) 0.96 (0.76–1.21) NR: not reached; HR/OR are NIVO+RELA vs NIVO+IPI.