170TiP A phase I study to characterize the safety and tolerability of MP0317, a tumor targeting FAP dependent CD40 agonist DARPin®, in patients with relapsed/refractory solid tumors

Abstract

Despite initially promising signs of efficacy, the clinical benefit of CD40 agonists has been limited by toxicity. Strategies to enable targeted CD40 activation are required. Fibroblast activating protein (FAP) is highly expressed in many solid tumors but less so in normal tissue. The DARPin® molecule MP0317 utilizes FAP binding and CD40 activating domains to trigger immune activation only in the presence of FAP. By localizing CD40 activation to the tumor, MP0317 could potentially reduce the risk of systemic side effects, e.g., hepatotoxicity, thereby improving the therapeutic index of CD40 agonism.