NCT06625515

First-in-Human Study of ATX-559, an Oral Inhibitor of DHX9, in Patients With Advanced or Metastatic Solid Tumors, and Molecularly Defined Cancers

A Phase 1/2, Open-Label, Dose-Escalation and Expansion First-In-Human Study of ATX-559, an Oral Inhibitor of the Helicase DHX9, in Patients With Locally Advanced or Metastatic Solid Tumors and Molecularly Defined Cancers

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 17 (actual)
• Sponsor: Accent Therapeutics · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this study is to identify a safe and tolerated dose of the orally administered DHX9 inhibitor ATX-559. In addition, this study will evaluate the pharmacokinetics, pharmacodynamics and preliminary antitumor activity of ATX-559 in patients with advanced solid tumors and molecularly defined cancers.

Detailed description

ATX-559 is an oral drug that inhibits a protein called DHX9, a multi-functional RNA helicase that is involved in the maintenance of genomic stability by resolving DNA/RNA secondary structures that may lead to DNA replication stress and DNA damage in certain molecularly defined cancers. ATX-559 has been shown preclinically to induce robust anti-tumor activity of a variety of different solid tumors, including models with BRCA deficiency and microsatellite instability-high (MSI-H) and/or deficient mismatch repair (dMMR). This is a first-in-human, Phase 1, open-label, single-arm, dose-escalation and expansion study to: Evaluate the safety profile of ATX-559 and determine the recommended phase 2 dose (RP2D). In addition, the study aims to characterize the PK, PD, and preliminary anti-tumor activity of orally administered ATX-559. Exploratory objectives include examination of biomarker responses in relationship to ATX-559 exposure. Patients with molecularly selected locally advanced or metastatic solid tumors (for example, BRCA1- or BRCA2-deficient breast cancer and solid tumors with microsatellite instability (MSI-H) and/or deficient mismatch repair (dMMR) will be enrolled to preliminarily assess the anti-tumor effect, and further examine the safety and PK of ATX-559 at the RP2D.

Conditions

• Advanced Solid Tumors
• Breast Cancer Recurrent
• Colorectal Cancer Metastatic
• Colon Cancer
• Rectal Adenocarcinoma
• Endometrial Cancer

Interventions

Type	Name	Description
DRUG	ATX-559	DHX9 tablets will be taken orally

Timeline

• Start date: 2024-10-11
• Primary completion: 2026-01-09
• Completion: 2026-01-09
• First posted: 2024-10-03
• Last updated: 2026-02-24

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study