BACKGROUND: Prolgolimab is the first Russian original PD-1 inhibitor to treat one of the most aggressive types of cancer – metastatic or unresectable melanoma. Currently, there are no head-to-head trials comparing efficacy of prolgolimab with other immune therapies for advanced melanoma.

OBJECTIVES: This study implements a matching-adjusted indirect comparison (MAIC) technique to assess the comparative efficacy of prolgolimab with other PD-1 inhibitors in monotherapy (nivolumab, pembrolizumab) and in combination with CTLA-4 inhibitor (nivolumab + ipilimumab) in patients with advanced melanoma.

METHODS: In the absence of a common comparator between trials, unahchored MAIC methodology was applied. Patient-level data for prolgolimab from Phase II-III MIRACULUM trial were re-weighted to match identified potential prognostic factors and effects modifiers from published summary efficacy results of pembrolizumab (KEYNOTE-006), nivolumab (CheckMate-066), and nivolumab + ipilimumab (CheckMate-067) trials. Matched-on characteristics included Eastern Cooperative Oncology Group (ECOG) status (0 vs 1-2), PD-L1 status (positive/negative), LDH level (normal/elevated), brain metastases (yes/no). Pairwise comparisons using hazard ratios (HRs) were performed for overall survival (OS) and progression-free survival (PFS) after 1 year from treatment initiation. To calculate HRs, the one-sample log-rank test was used. Statistical significance was assessed based on a chi-square distribution.

RESULTS: Effective sample sizes (ESS) of the prolgolimab patients were 52.40 after matching to pembrolizumab, 43.59 after matching to nivolumab, and 36.49 after matching to nivolumab + ipilimumab. No significant differences (all p > 0.05) were etablished between prolgolimab and other considered immune therapies for both OS and PFS outcomes.

CONCLUSIONS: In this unanchored MAIC, prolgolimab showed comparable efficacy with other PD-1 inhibitors in monotherapy (nivolumab, pembrolizumab) and in combination with CTLA-4 inhibitor (nivolumab + ipilimumab) based on OS and PFS after 1 year from therapy initiation in patients with metastatic or unresectable melanoma. This analysis may be relevant for clinical decision-making, thus improving the treatment of patients with advanced melanoma.