First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors
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)