Development

Arvinas enters immuno-oncology with HPK1 PROTAC degrader in Phase I/II trial

Arvinas enters immuno-oncology with HPK1 PROTAC degrader in Phase I/II trial

Arvinas, Inc. (Nasdaq: ARVN) dosed the first patient in a Phase I/II trial of ARV-6723, marking the New Haven, Connecticut-based company's entry into immuno-oncology with an oral PROTAC degrader of hematopoietic progenitor kinase 1 (HPK1).

HPK1 is a negative regulator of immune activation expressed across T cells, B cells, natural killer cells, and dendritic cells. ARV-6723 is designed to degrade the HPK1 protein rather than only inhibit its kinase activity, potentially disrupting both kinase-dependent and kinase-independent functions.

The ARV-6723-101 trial (NCT07749586) is evaluating ARV-6723 as monotherapy and in combination with pembrolizumab in adults with advanced solid tumors. Initial dose escalation is enrolling patients previously treated with an immune checkpoint inhibitor who have no suitable standard treatment options remaining.

No clinical efficacy or safety data are yet available. Arvinas previously reported preclinical antitumor activity for ARV-6723 across multiple tumor models, including models resistant to anti-PD-1 therapy, supporting evaluation as both monotherapy and in combination with checkpoint blockade.

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Arvinas said ARV-6723 is the first HPK1 PROTAC degrader to enter clinical development in the US and its first clinical-stage immuno-oncology program.

The program expands Arvinas's PROTAC pipeline beyond its existing oncology, neuroscience, and neuromuscular programs, which include ARV-393 targeting BCL6, ARV-806 targeting KRAS G12D, ARV-102 targeting LRRK2, and ARV-027 targeting polyglutamine-expanded androgen receptor.


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