Nivolumab + relatlimab (NIVO + RELA) in advanced melanoma: 5-year update of RELATIVITY-047.

Abstract

9532 Background: NIVO + RELA improved progression-free survival (PFS) vs NIVO in patients (pts) with advanced melanoma in the randomized, double-blind, phase 3 RELATIVITY-047 trial (NCT03470922), leading to regulatory approval as a fixed-dose combination (FDC). The combination also improved clinically meaningful efficacy outcomes (objective response rate [ORR], overall survival [OS], melanoma-specific survival [MSS]) vs NIVO. Here, we report 5-year trial outcomes that characterize long-term response durability and landmark survival. Methods: 714 pts were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg FDC or NIVO 480 mg intravenously every 4 weeks, as previously described. PFS per RECIST v1.1 (primary endpoint) was assessed by blinded independent central review (BICR); secondary endpoints included ORR per BICR and OS. MSS (censoring nonmelanoma-related deaths) was a post hoc analysis. Results: At data cutoff (25 Sept 2025), minimum potential follow-up was 57.3 months (mo; time from last pt randomization to clinical cutoff date). NIVO + RELA continued to show a clinically meaningful benefit vs NIVO for PFS, OS, MSS, and ORR (table). Improvements in absolute landmark survival rates were observed over 3, 4, and 5 years as follows: PFS, 4%, 7%, and 10%; OS, 7%, 9%, and 10%; MSS, 9%, 10%, and 13%. In addition, NIVO + RELA demonstrated consistent improvement in efficacy outcomes vs NIVO across the majority of key subgroups. Subsequent systemic therapy was received by 40% of pts treated with NIVO + RELA and 41% with NIVO. Secondary efficacy and biomarker analyses will be presented. Grade 3–4 treatment-related adverse events (TRAEs) occurred in 23% of pts treated with NIVO + RELA and 12% with NIVO; TRAEs (any grade) led to treatment discontinuation in 17% and 10% of pts, respectively. No new treatment-related deaths were reported since the 2-year analysis. Conclusions: With a follow-up of 5 years, first-line NIVO + RELA continued to demonstrate durable, clinically meaningful long-term improvements in PFS, OS, ORR, and MSS vs NIVO, with median MSS not reached for the combination. Across landmark timepoints, absolute separations in PFS, OS, and MSS rates were maintained and increased at the 5-year follow-up. Safety remained consistent with prior reports, with no new or unexpected safety signals. Clinical trial information: NCT03470922 . NIVO + RELA (n = 355) NIVO (n = 359) HR/ORR difference (95% CI) Median PFS, mo (95% CI) 10.2 (6.5–15.7) 4.6 (3.5–6.5) 0.77 (0.65–0.92) 60 mo PFS rate, % (95% CI) 29 (24–35) 19 (15–24) — Median OS, mo (95% CI) 54.8 (33.6–81.1) 33.2 (25.2–44.7) 0.78 (0.64–0.95) 60 mo OS rate, % (95% CI) 48 (43–53) 38 (33–43) — Median MSS, mo (95% CI) NE (NE–NE) 47 (34–65) 0.71 (0.57–0.88) 60 mo MSS rate, % (95% CI) 58 (52–63) 45 (40–51) — ORR, % (95% CI) 44 (39–49) 34 (29–39) 10 (3–17) Descriptive analyses; minimum follow-up: 57.3 mo. HR, hazard ratio; NE, not estimable.