Tumor-localized CD40 agonism with MP0317, a FAP x CD40 DARPin, reprograms the tumor microenvironment in patients with advanced solid tumors: an open-label, nonrandomized, dose-escalation phase 1 study

Researchers led by Steeghs have published results from a first-in-human phase 1 dose-escalation trial of MP0317, a novel bispecific DARPin molecule that simultaneously targets fibroblast activation protein (FAP) on tumor stroma and the immune-stimulatory receptor CD40. The study demonstrated that tumor-localized CD40 agonism can reprogram the tumor microenvironment in patients with advanced solid tumors, while providing safety, pharmacokinetic, and pharmacodynamic data. This approach aims to activate anti-tumor immunity precisely within the tumor while avoiding systemic toxicity associated with conventional CD40 agonist antibodies. The findings, published in Nature Cancer, support further clinical development of FAP-targeted immune agonists as a strategy to overcome immunosuppressive tumor microenvironments.