NEW HAVEN, Conn. — September 28, 2026
Arvinas, Inc. announced that the first participant has been dosed in the Phase 1/2 clinical trial of ARV-6723, an investigational oral PROTAC designed to degrade hematopoietic progenitor kinase 1 (HPK1) in patients with advanced solid tumors. ARV-6723 represents Arvinas’ first clinical candidate in immuno-oncology and is described by the company as the first HPK1 PROTAC degrader to enter clinical development in the United States. The candidate is designed to selectively remove HPK1, a negative regulator of immune activation expressed across T cells, B cells, natural killer cells and dendritic cells. By targeting the protein itself and its signaling scaffolding, Arvinas aims to address both kinase-dependent and kinase-independent functions of HPK1 and potentially enhance antitumor immune activity..
ARV-6723 Targets HPK1 Through Protein Degradation
HPK1 plays an important role in regulating immune-cell activation and shaping the tumor microenvironment, making it an area of interest for immuno-oncology drug development. Arvinas designed ARV-6723 using its PROTAC targeted protein degradation platform to induce selective degradation of HPK1 rather than simply inhibit its enzymatic activity. In preclinical studies, ARV-6723 demonstrated potent and selective HPK1 degradation, enhanced immune activity and antitumor effects across tumor models with different levels of immune responsiveness. The company also reported activity in multiple models resistant to anti-PD-1 treatment. In seven preclinical models, ARV-6723 showed meaningful single-agent activity in settings where neither an HPK1 inhibitor nor anti-PD-1 therapy produced benefit. These findings provided the rationale for evaluating ARV-6723 as both a monotherapy and in combination with immune checkpoint inhibition, although the preclinical findings do not establish clinical efficacy in patients.
Global Phase 1/2 Study Evaluates Monotherapy and Combination
The ARV-6723-101 Phase 1/2 trial, identified as NCT07749586, is a global, multicenter first-in-human study evaluating the safety, pharmacokinetics, pharmacodynamics and preliminary antitumor activity of orally administered ARV-6723 in adults with advanced solid tumors. The study will initially assess ARV-6723 as a monotherapy before evaluating the candidate in combination with pembrolizumab, an anti-PD-1 therapy. Investigators will examine whether sustained HPK1 degradation can translate into measurable antitumor effects while establishing the candidate’s clinical safety and pharmacological profile. The initial monotherapy cohort is enrolling patients who have previously received an immune checkpoint inhibitor and have no suitable standard treatment options. The study is therefore designed to generate early clinical information in patients whose tumors have already been exposed to checkpoint blockade, including populations in which treatment resistance remains an important development challenge.
Advertisement
Arvinas Expands Targeted Protein Degradation Into Immuno-Oncology
The ARV-6723 program expands Arvinas’ targeted protein degradation platform into immuno-oncology while adding another clinical program to the company’s broader pipeline. Arvinas and Pfizer previously developed the first FDA-approved PROTAC, demonstrating the clinical potential of targeted protein degradation as a therapeutic approach. The company is now advancing additional investigational programs, including ARV-393, targeting BCL6 in relapsed or refractory non-Hodgkin lymphoma; ARV-102, targeting LRRK2 in neurodegenerative disorders; ARV-027, targeting polyglutamine-expanded androgen receptor in spinal-bulbar muscular atrophy; and ARV-806, targeting KRAS G12D in solid tumors. With ARV-6723 now entering human clinical testing, Arvinas is evaluating whether targeted degradation of an immune-regulatory protein can provide a new approach to enhancing antitumor immunity, including in tumors that have shown resistance to existing immune checkpoint therapies.
Source Arvinas press release
