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

NCT ID: NCT06625515

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-11

Study Completion Date

2027-02-28

Brief Summary

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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

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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

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

Keywords

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MSI-high/dMMR tumors BRCA1 mutation BRCA2 mutation DHX9 dMMR deficient mismatch repair microsatellite instability

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose escalation

Subjects will be enrolled at various doses or schedules of ATX-559 to identify the RP2D

Group Type EXPERIMENTAL

ATX-559

Intervention Type DRUG

DHX9 tablets will be taken orally

Dose Expansion: MSI-H/dMMR solid tumors

Group Type EXPERIMENTAL

ATX-559

Intervention Type DRUG

DHX9 tablets will be taken orally

Dose Expansion: BRCA1- or BRCA2-deficient HER2-negative breast cancer

Group Type EXPERIMENTAL

ATX-559

Intervention Type DRUG

DHX9 tablets will be taken orally

Interventions

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ATX-559

DHX9 tablets will be taken orally

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Patients with histologically confirmed solid tumors who have locally recurrent or metastatic disease
* Refractory to or relapsed after all standard therapies with proven clinical benefit, unless as deemed by the Investigator, the subject is not a candidate for standard treatment, there is no standard treatment, or the subject refuses standard treatment after expressing an understanding of all available therapies with proven clinical benefit
* For the expansion cohorts, participants must have histological confirmation of the specified tumor types:
* BRCA1 or BRCA2 deficient, HER2 negative metastatic breast cancer
* dMMR or MSI-H with unresectable or metastatic solid tumors
* There is no limit to the number of prior treatment regimens
* Have measurable or evaluable disease
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Exclusion Criteria

* Clinically unstable central nervous system (CNS) tumors or brain metastasis
* Any other concurrent anti-cancer treatment
* Has undergone a major surgery within 3 weeks of starting study treatment
* Medical issue that limits oral ingestion or impairment of gastrointestinal function that is expected to significantly reduce the absorption of ATX-559
* Clinically significant (ie, active) or uncontrolled cardiovascular disease
* Unable to transition off strong or moderate CYP2C8 inhibitors or inducers
* Pregnancy or intent to breastfeed or conceive a child within the projected duration of treatment
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Accent Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Colorado Cancer Center - Anschutz Medical Campus,

Aurora, Colorado, United States

Site Status RECRUITING

Stephenson Cancer Center at OU Medicine

Oklahoma City, Oklahoma, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

NEXT Oncology

San Antonio, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jason Sager, MD

Role: CONTACT

Phone: (339) 970-7400

Email: [email protected]

Priya Rajaratnam

Role: CONTACT

Phone: (339) 970-7383

Email: [email protected]

Facility Contacts

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Annie Preas

Role: primary

Christina Caldwell

Role: primary

https://sarahcannon.com/about/connect-with-us.dot

Role: primary

Timothy Yap, MD, PhD

Role: primary

Jordan Georg

Role: primary

Other Identifiers

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ATX-559-001

Identifier Type: -

Identifier Source: org_study_id