Background: In the phase 2/3 RELATIVITY-047 trial, NIVO + RELA as a fixed-dose combination (FDC) significantly improved the primary endpoint of progression-free survival (PFS) versus NIVO in patients (pts) with previously untreated metastatic or unresectable melanoma. Secondary endpoints showed a clinically meaningful improvement in overall survival (OS), although not statistically significant, and a higher objective response rate (ORR). As previously reported, PFS and OS favored NIVO + RELA over NIVO across prespecified stratification factors (LAG-3 expression, PD-L1 expression, BRAF V600 mutation status, and metastasis stage). Here we report the first disclosure of ORR analyzed by prespecified stratification factors and OS and ORR in additional subgroups. Methods: Pts were randomized 1:1 to receive NIVO 480 mg + RELA 160 mg FDC or NIVO 480 mg intravenously Q4W. The primary endpoint was PFS per RECIST v1.1 assessed by blinded independent central review (BICR). Secondary endpoints were OS and ORR by BICR, tested in hierarchy. Exploratory analyses were performed for PFS, OS, and ORR by prespecified subgroups. Results: PFS continued to favor NIVO + RELA over NIVO across key subgroups. OS and ORR also favored NIVO + RELA over NIVO across key subgroups including those associated with poor prognosis (Table). ORR favored NIVO + RELA over NIVO for pts with LAG-3 expression ≥ 1% (47% vs 35%) and < 1% (31% vs 24%), PD-L1 expression ≥ 1% (53% vs 45%) and < 1% (36% vs 24%), and BRAF wild-type (43% vs 34%) and mutant (43% vs 31%) melanoma, respectively. Additional key prespecified subgroups will be presented. In all treated pts, NIVO + RELA maintained a manageable safety profile with no new or unexpected safety signals. Conclusions: NIVO + RELA was favored over NIVO across key subgroups for PFS, OS, and ORR, and findings appeared consistent with outcomes in the overall population. NIVO + RELA had a favorable benefit-risk profile. Clinical trial information: NCT03470922.

CI, confidence interval; HR, hazard ratio; LDH, lactate dehydrogenase; mOS, median overall survival; NR, not reached; N, nivolumab; N+R, nivolumab plus relatlimab; n, number of patients; Q3, quartile 3; R, relatlimab; ULN, upper limit of normal. *AJCC v8; ^†Tumor burden quartile as determined by BICR at baseline; ̂Unstratified HR was 0.81 and stratified HR was 0.80.