A phase I study targeting the APE1/Ref-1 redox signaling protein with APX3330: first clinical agent targeting APE1/Ref-1 in cancer.

ABSTRACT:

Background

APX3330 is an oral agent targeting the redox signaling activity of APE1/Ref-1 (Ref-1), a key regulator of transcription factors involved in inflammation and tumorigenesis. APX3330 selectively inhibits Ref-1's redox function without affecting its DNA repair role. This Phase 1, multicenter, open-label, dose-escalation study in advanced solid tumors was aimed at determining the recommended Phase 2 dose (RP2D) while assessing safety, pharmacokinetics, and biomarker evidence of target engagement.

Methods

Nineteen cancer patients were treated, with eight completing follow-ups. Subjects received APX3330 orally twice daily in 21-day cycles, starting at 240 mg/d and escalating in 120 mg/d increments. Adverse event (AE) monitoring followed a 1 pt/cohort approach until a >G2

SUBMITTER: Kelley MR 

PROVIDER: S-EPMC12857578 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature