Background: Nivolumab and relatlimab-rmbw (R/N) combination demonstrated superior efficacy to nivolumab alone in patients with previously untreated metastatic or unresectable melanoma. Sparse data exists on the efficacy of this combination in patients with melanoma that relapsed after,or was resistant to treatment with PD-1 inhibitors. Methods: We conducted a retrospective study of patients with unresectable or metastatic melanoma whose disease recurred or progressed on/after prior PD-1 inhibitor who received R/N at Inova Schar Cancer Institute. Efficacy endpoint was objective response using modified RECIST1.1. Unconfirmed complete response (CR) or partial response (PR) were included in objective response rate (ORR). Patients whose Positron Emission Tomography (PET) scan showing complete metabolic resolution of metastatic sites were also considered CR. Patients who had rapid clinical progression and didn’t have repeat radiologic studies were considered to have progressive disease (PD). Patients who underwent radiation to target lesions were considered non-evaluable (NE). Results: From Sep 2021 through Dec 2022, a total of 32 patients (19 male) received R/N including 8 unresectable stage III melanomas and 24 stage IV melanomas (M1a: 4, M1b: 4, Mc1: 5, M1d: 10). Median age was 67 (39-88), and 12 (38%) had BRAF mutation. Median number of prior therapies was 2 (range: 1-7) including anti-CTLA4 antibody in 22 and BRAF/MEK inhibitor in 8. Nine patients (28%) had ≥ 3 prior therapies. Among 30 patients evaluable for response, ORR was 33% (4 CR, 6 PR). Three had stable disease (SD), and 16 had PD including 2 with rapid clinical progression. Response by subgroup is included in table. Conclusions: R/N shows clinically meaningful antitumor activity in patients who received prior PD-1 inhibitor in real world setting. Additional clinical data of R/N in PD-1 inhibitor relapsed or refractory patients are needed to validate the results of this single-center study.