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

Trial Title: 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

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

Conditions: Official terms:
Endometrial Neoplasms

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

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Sequential Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: ATX-559
Description: DHX9 tablets will be taken orally
Arm group label: Dose Expansion: BRCA1- or BRCA2-deficient HER2-negative breast cancer
Arm group label: Dose Expansion: MSI-H/dMMR solid tumors
Arm group label: Dose escalation

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.

Criteria for eligibility:
Criteria:
Key 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 Key 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 Other inclusion and exclusion criteria as defined in the study protocol

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: NEXT Oncology

Address:
City: San Antonio
Zip: 78229
Country: United States

Status: Recruiting

Contact:
Last name: Jordan Georg

Phone: (210) 580-9521
Email: jgeorg@nextoncology.com

Contact backup:
Last name: Anthony Tolcher, MD

Start date: October 2024

Completion date: February 2027

Lead sponsor:
Agency: Accent Therapeutics
Agency class: Industry

Source: Accent Therapeutics

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06625515