Tumor-localized CD40 agonism with MP0317, an FAPxCD40 DARPin, reprograms the tumor microenvironment - results of a Phase 1 monotherapy study

This Phase 1 dose-escalation study evaluated MP0317 (FAP x CD40 DARPin) in adults with advanced solid tumors (n=46; 0.03–10 mg/kg IV weekly or every-3-weeks). Primary outcome measure was safety; secondary/exploratory outcome measures included antitumor activity, pharmacokinetics and pharmacodynamics. Most treatment-related adverse events were of Grade 1–2 (95%) and a maximum tolerated dose was not reached. One patient achieved an unconfirmed partial response and 14 patients stable disease. MP0317 serum pharmacokinetics confirmed extended half-life properties; terminal half-life estimates increased with dose and ranged from 21.8–120 hours. Paired tumor biopsies confirmed colocalization of MP0317 with FAP and CD40. Activation of the CD40 pathway in the tumor microenvironment was shown by increased infiltration of antigen-presenting, plasma, and T follicular helper cells, dendritic cell maturation, IFN signaling, and circulating immune markers. Collectively, these data confirm a favorable safety profile for MP0317 and support further clinical evaluation in combination with complementary immunotherapies.