9504 Background: Adjuvant NIVO significantly prolonged recurrence-free survival (RFS) over PBO in stage IIB/C melanoma in the randomized, phase III Checkmate 76K trial (HR; 95% CI: 0.42 [0.30–0.59]). For the first time, select BMs and their association with RFS were analyzed in early-stage melanoma treated with an anti-PD-1 agent. Methods: Baseline primary tumor and serum BMs were analyzed, including interferon gamma-related gene expression signature (IFNγ-sig), TMB, BRAF mutation, % intratumoral CD8+ T cells, tumor cell PD-L1 expression, and serum CRP levels. BMs were evaluated as continuous variables (high vs low levels) and dichotomized by median or prespecified cutoffs. HRs were estimated using a Cox proportional hazards model. Results: Analysis of continuous BM levels within treatment arms showed that higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels were associated with prolonged RFS with NIVO but not PBO. The same trend was observed in the dichotomized analyses. No clear association between PD-L1 expression and RFS was identified in either arm. Benefit of NIVO over PBO was seen across all BM subgroups, including by BRAFV600 mutation status. Patients with higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels showed numerically greater relative benefit with NIVO, although CIs overlapped (Table). Conclusions: Higher IFNγ-sig, TMB, and % CD8+ T cells, and lower CRP levels were associated with longer RFS with NIVO treatment. No BMs assessed were prognostic for RFS in the PBO arm, in contrast to previous reports in melanoma. Prolonged RFS was seen in patients treated with NIVO over PBO across levels of BMs, and irrespective of BRAF mutational status. Composite analyses of BMs with clinical and histopathologic factors will be evaluated for their potential to optimize risk:benefit stratification for NIVO in this patient population. Clinical trial information: NCT04099251 . [Table: see text]