iSCIB1+ in Combination With Ipilimumab and Nivolumab as First-Line Treatment for Advanced Unresectable Melanoma

This is a multicenter, randomized, double-blind, placebo-controlled Phase 3 study evaluating the efficacy and safety of iSCIB1+ in combination with nivolumab and ipilimumab as first-line treatment for adults with advanced unresectable Stage III or Stage IV melanoma who express specific human leukocyte antigen (HLA) types. Checkpoint inhibitor therapy has significantly improved outcomes for patients with advanced melanoma; however, many patients still experience disease progression. iSCIB1+ is a DNA-based therapeutic cancer vaccine designed to enhance immune recognition of melanoma-associated antigens and may improve the depth and durability of anti-tumor responses when used alongside checkpoint inhibition. Approximately 550 participants will be randomized in a 1:1 ratio to receive either: iSCIB1+ plus nivolumab and ipilimumab, or Placebo plus nivolumab and ipilimumab. The primary objective is to determine whether the addition of iSCIB1+ improves progression-free survival (PFS) compared with placebo when both are administered in combination with nivolumab and ipilimumab. Secondary objectives include evaluation of: Overall survival (OS) Objective response rate (ORR) Duration of response (DoR) Disease control rate (DCR) Safety and tolerability Patient-reported quality of life outcomes The study will also explore immune and biomarker responses in selected participants to better understand the relationship between vaccine-induced immune responses and clinical outcomes. Participants will continue to be followed for disease progression, survival, safety, and other outcomes for up to four years after randomization.