Sotigalimab (intratumoral CD40 agonist) + pembrolizumab drives 50% ORR and abscopal responses in CPI‑naïve metastatic melanoma

Sotigalimab is an intratumoral, agonistic anti‑CD40 antibody designed to activate antigen-presenting cells (APCs) and “in situ” prime T cells; here it was combined with pembrolizumab (anti‑PD‑1) in a Phase I/II study in CPI‑naïve metastatic melanoma (NCT02706353; n=32). At the RP2D, ORR was 50% with DCR 92%, including ORR 67% in injected lesions and 50% in non-injected lesions (suggesting a systemic/abscopal effect). Safety was described as well tolerated, with sotigalimab-related AEs mainly injection-site reactions, pruritus, and fatigue; however, the abstract does not report Grade 3+ TRAEs or discontinuation rates—making cross-trial safety comparison difficult (pembrolizumab monotherapy in KEYNOTE‑006 achieved ~33% ORR with ~10–13% Grade 3–4 TRAEs).