Garralda, E. (Elena), Geva, R. (Ravit), Ben-Ami, E. (Eytan), Maurice-Dror, C. (Corinne), Calvo, E. (Emiliano), LoRusso, P. (Patricia), Türec, Ö. (Özlem), Niewood, M. (Michelle), Sahin, U. (Ugur), Jure-Kunkel, M. (María), Forssmann, U. (Ulf), Ahmadi, T. (Tahamtan), and Melero, I. (Ignacio)
Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L) 1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381).