A first-in-human Phase I trial of an Fc-optimized CD40 agonistic antibody, 2141.V11, delivered intratumorally, has demonstrated preliminary clinical efficacy in metastatic cancer patients. Among 12 treated, six exhibited tumor shrinkage, with two complete remissions, including responses in non-injected tumor sites. These findings, published in Cancer Cell, suggest systemic immune activation following localized delivery, offering a novel immunotherapeutic approach with promising safety and efficacy profiles.