Intratumoral sotigalimab with pembrolizumab induces rapid activation of antigen presenting cells and drives anti-tumor responses in non-injected tumors in metastatic melanoma: A phase I/II study
Mené sur 32 patients atteints d'un mélanome métastatique, cet essai de phase I/II évalue la sécurité et l'efficacité, du point de vue du taux de réponse objective, d'une administration intratumorale de sotigalimab en association avec le pembrolizumab
Immune checkpoint blockers (ICBs) improve outcomes in metastatic melanoma (MM), but resistance limits benefit. This phase I/II (NCT02706353) study evaluated intratumoral sotigalimab (anti-CD40 agonist) with pembrolizumab in 32 ICB-naïve MM patients. Primary endpoints were safety, and objective response rate (ORR). Sotigalimab was well tolerated. At the recommended phase 2 dose (RP2D), the ORR was 50% and the disease control rate (DCR) was 92%, with ORR of 67% in injected and 50% in non-injected tumors. Multiomic analyses of tumor and blood showed sotigalimab effectively engaged the CD40 pathway, boosting infiltration and activation of myeloid cells, including CD11c+DC-LAMP+ dendritic cells (DCs) and macrophages. The combination therapy activated innate and adaptive immunity in injected tumors and cytotoxic responses in non-injected tumors. TCR sequencing showed increased T-cell clonality with expanded new clones shared across tumors. Clinical responses correlated with these immunologic changes, but not with baseline features associated with response to anti-PD1 monotherapy.
Cancer Discovery , article en libre accès, 2026