On September 28, 2026 Arvinas, Inc. (Nasdaq: ARVN), a clinical-stage biotechnology company creating a new class of drugs based on targeted protein degradation, reported that the first participant has been dosed in its Phase 1/2 clinical trial of ARV-6723, an investigational, oral PROteolysis TArgeting Chimera (PROTAC) designed to degrade hematopoietic progenitor kinase 1 (HPK1) in advanced solid tumors. ARV-6723 is Arvinas’ first clinical candidate in immuno-oncology (IO) and the first HPK1 PROTAC degrader to enter the clinic in the United States.
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HPK1 acts as a negative regulator of immune activation and is expressed across multiple cell types including T cells, B cells, natural killer cells, and dendritic cells, making it a compelling IO target. HPK1 also plays an important role in shaping the tumor microenvironment. ARV-6723 is designed to degrade and remove the HPK1 protein and its signaling scaffolding, potentially addressing functions of HPK1 that may not be fully addressed by traditional inhibitors.
In preclinical studies, ARV-6723 demonstrated potent and selective HPK1 degradation, enhanced immune activity, and antitumor activity as a single agent and in combination with an immune checkpoint inhibitor across tumor models with differing levels of immune responsiveness, including multiple anti-PD-1-resistant models. Notably, in seven preclinical models, ARV-6723 demonstrated meaningful single-agent activity where neither an HPK1 inhibitor nor anti-PD-1 therapy showed benefit. These data support the clinical evaluation of ARV-6723 both as monotherapy and in combination with an anti-PD-1 therapy.
"The advancement of ARV-6723 into the clinic represents an important step in expanding the application of targeted protein degradation into immuno-oncology," said Randy Teel, Ph.D., President and Chief Executive Officer at Arvinas. "Resistance to immunotherapy remains a significant challenge; to date, combinations targeting other immune pathways have not provided a reliable way to prevent or reverse it. The encouraging preclinical data for ARV-6723 – including activity in models resistant to immune checkpoint inhibitors – support clinical investigation of its potential to address this unmet need for patients."
The ARV-6723-101 Phase 1/2 clinical trial (NCT07749586) is a global, multicenter trial designed to assess the safety, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of orally administered ARV-6723 as a monotherapy or in combination with pembrolizumab in adults with advanced solid tumors. The first-in-human trial will initially evaluate the safety of ARV-6723 as a monotherapy treatment and subsequently in combination with an anti-PD-1 therapy, while also evaluating whether deep and sustained HPK1 degradation translates into meaningful antitumor effects in patients. The initial monotherapy cohort of this trial is enrolling patients who have received a prior immune checkpoint inhibitor and have no suitable standard treatment options.
(Press release, Arvinas, SEP 28, 2026, View Source [SID1234671122])