Sotigalimab (intratumoral CD40 agonist) + pembrolizumab delivers 50% ORR and abscopal activity in metastatic melanoma

Sotigalimab (APX005M) is an intratumoral CD40 agonistic antibody designed to activate antigen-presenting cells (APCs); here it was combined with systemic pembrolizumab (anti–PD-1) in an ICB-naïve metastatic melanoma Phase I/II trial (NCT02706353) (n=32). At the RP2D, ORR was 50% with DCR 92%, including ORR 67% in injected lesions and 50% in non-injected lesions—numerically above historical pembrolizumab monotherapy ORR ~33–34% in advanced melanoma, though this is a small, early-phase, non-randomized dataset. Multi-omic profiling showed on-target CD40 pathway engagement with increased/activated intratumoral myeloid populations (including CD11c+DC-LAMP+ DCs and macrophages), plus increased TCR clonality and emergence of new shared T-cell clones across tumors; safety was described as “well tolerated” in the abstract, but rates of Grade ≥3 AEs/discontinuations were not provided.