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

NCT06625515 | Terminated Phase 1 FDA Drug

• 1 other identifier: ATX-559-001
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-559

  Identification of a tolerable and safe dose for expansion cohorts based on dose limiting toxicities

  12 months

• Safety and tolerability of ATX-559

  Incidence of adverse events graded according to CTCAE v5.0

  12 months

Secondary Outcomes (5)

• Preliminary evidence of antitumor activity

  12 months

• Pharmacodynamic activity of ATX-559 in blood over time via measurement of circBRIP1 RNA levels

  12 months

• Maximum observed plasma concentration of ATX-559 (Cmax)

  12 months

• Calculated time to reach maximum observed plasma concentration (Tmax)

  12 months

• Calculated area under the plasma concentration-time curve of ATX-559 (AUC0-t)

  12 months

Study Arms (3)

Dose escalation

EXPERIMENTAL

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

Drug: ATX-559

Dose Expansion: MSI-H/dMMR solid tumors

EXPERIMENTAL

Drug: ATX-559

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

EXPERIMENTAL

Drug: ATX-559

Interventions

ATX-559 DRUG

DHX9 tablets will be taken orally

Dose Expansion: BRCA1- or BRCA2-deficient HER2-negative breast cancer; Dose Expansion: MSI-H/dMMR solid tumors; Dose escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Accent Therapeutics: lead

Study Sites (5)

University of Colorado Cancer Center - Anschutz Medical Campus,

Aurora, Colorado, 80045, United States

Location

Stephenson Cancer Center at OU Medicine

Oklahoma City, Oklahoma, 73104, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Colonic Neoplasms; Rectal Neoplasms; Endometrial Neoplasms; Microsatellite Instability

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2024
• First Posted: October 3, 2024
• Study Start: October 11, 2024
• Primary Completion: January 9, 2026
• Study Completion: January 9, 2026
• Last Updated: February 24, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)