A Phase I clinical trial demonstrated remarkable tumor regression in metastatic cancer patients using an Fc-optimized CD40 agonist antibody injected directly into tumors. Six out of twelve patients showed tumor shrinkage including non-injected sites, with two achieving complete remission. This agent stimulates systemic antitumor immunity by inducing tertiary lymphoid structures, offering potential for treating advanced and refractory cancers with minimal systemic toxicity.