Background: In RELATIVITY-047 (NCT03470922), NIVO + RELA demonstrated a statistically significant progression-free survival (PFS) benefit vs NIVO; there was an observed improvement in overall survival (OS) although it was not statistically significant. The combination also had a descriptively higher confirmed objective response rate (ORR) assessed by blinded independent central review (BICR) vs NIVO. Here we report updated descriptive analyses (efficacy, safety, and secondary analyses) with longer (~ 2 years) follow-up. Methods: Patients were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg fixed-dose combination or NIVO 480 mg every 4 weeks, as previously described. Primary endpoint of PFS per RECIST v1.1 was assessed by BICR; secondary endpoints included OS and ORR per BICR. Exploratory analyses were performed for melanoma-specific survival (MSS; defined as death due to melanoma, with censoring of deaths due to other causes) and efficacy outcomes on subsequent systemic therapy. Results: Patients received NIVO + RELA (n = 355) or NIVO (n = 359). Median follow-up was 25.3 months in this updated analysis (minimum follow-up, 21.0 months). NIVO + RELA continued to show a benefit over NIVO for PFS, OS and ORR (Table). A similar improvement was also observed in MSS. NIVO + RELA was generally favored over NIVO across key subgroups (consistent with previous reports). Subsequent systemic therapy was received by 131 (36.9%) and 136 (37.9%) patients in the NIVO + RELA and NIVO arms, respectively. Treatment-related adverse events (TRAEs; any grade) leading to treatment discontinuation were observed in 61 (17.2%) and 31 (8.6%) patients on NIVO + RELA and NIVO, respectively. Grade 3–4 TRAEs were observed in 78 (22.0%) patients on NIVO + RELA and 43 (12.0%) patients on NIVO. In total, there were 6 treatment-related deaths (NIVO + RELA, n = 4; NIVO, n = 2); no new treatment-related deaths have been reported since the last analysis. Conclusions: With 12.3 months of additional follow-up, a consistent benefit was observed with NIVO + RELA vs NIVO for PFS, OS and ORR in the ITT population, as well as in key patient subgroups. MSS was longer with NIVO + RELA compared with NIVO. The safety profile of NIVO + RELA remained consistent with previous reports, with no new or unexpected safety signals. Efficacy outcomes on subsequent systemic therapy (by type of subsequent therapy, including PD-L1/CTLA-4) will be presented. Clinical trial information: NCT03470922.