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ARV-6723 + pembrolizumab is an investigational combination regimen consisting of ARV-6723, an orally bioavailable proteolysis-targeting chimera (PROTAC) designed to degrade hematopoietic progenitor kinase 1 (HPK1), and pembrolizumab (Keytruda), an intravenous or subcutaneous anti-programmed cell death protein 1 (PD-1) monoclonal antibody. HPK1 is a key negative regulator of immune activation expressed across various immune cells, including T cells, B cells, natural killer cells, and dendritic cells. By degrading HPK1, ARV-6723 removes both its kinase-dependent and kinase-independent scaffolding functions, potentially reversing immune suppression in the tumor microenvironment. Pembrolizumab blocks the interaction between PD-1 and its ligands (PD-L1 and PD-L2), thereby unleashing T-cell-mediated antitumor activity. The combination of these two immunotherapies is designed to synergistically enhance immune activation and overcome resistance to checkpoint inhibition. Developed by Arvinas, the combination is being evaluated in a Phase 1/2 clinical trial (NCT07749586) for the treatment of patients with advanced solid tumors.
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