BCD-217-2/OCTAVA (NCT05732805) is an international, multi-center, randomized, double-blind, placebo-controlled phase III study conducted to access the efficacy and safety of prolgolimab+nurulimab (BCD-217) combination therapy with continued prolgolimab therapy compared to prolgolimab monotherapy as 1st line treatment for patients (pts) with unresectable/metastatic melanoma. BCD-217 is a fixed-dose combination of nurulimab (aCTLA-4, 5 mg/ml) and prolgolimab (aPD-1, 15 mg/ml) was recently approved as the 1st line treatment for mM. Here we present the primary analysis of the study. Pts with unresectable/metastatic cutaneous melanoma with no previous therapy for metastatic disease were randomized in 2 treatment arms: combination drug containing nurulimab (1 mg/kg) and prolgolimab (3 mg/kg) at a dose of 0.2 ml/kg Q3W during the first 4 blinded infusions (NURU+PROLGO arm). PROLGO arm received prolgolimab monotherapy at a dose of 3 mg/kg Q3W during the first 4 blinded infusions. Then both groups received prolgolimab maintenance up to 2 years. The primary endpoint of the study was progression-free survival (PFS).  271 pts were randomized to NURU+PROLGO (n=135) or PROLGO (n=136) arms. After the median of 15.8 mo follow-up the mPFS was 15.4 (8.4; ND) mo in the NURU+PROLGO arm and 7.4 (4.3; ND) mo in the PROLGO arm (95% CI, HR 0.66 (0.47; 0.93), iRECIST). mOS was not reached in both groups (95% CI, HR 0,88, (0.50; 1.55)). 12-mos OS was 84% in each arm. Grade 3–4 TRAEs were reported in 16.3% of pts in NURU+PROLGO arm vs 14.0% receiving PROLGO arm. Treatment discontinuation due to AE was reported in 9,6% vs 4,4% of cases for NURU+PROLGO and PROLGO arms, respectively.  The fixed-dose combination of NURU+PROLGO demonstrated the efficacy over mono-iPD-1 in pts with metastatic/unresectable cutaneous melanoma as 1st line therapy. Overall, a favorable safety profile demonstrated that fixed-dose combination of NURU+PROLGO improve efficacy while maintaining safety.