ATX-559 for Cancer

Recruiting at 7 trial locations

Overseen By Priya Rajaratnam

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Accent Therapeutics

Must not be taking: CYP2C8 inhibitors, CYP2C8 inducers

Disqualifiers: CNS tumors, Cardiovascular disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new oral treatment called ATX-559 for individuals with advanced solid tumors. The goal is to determine a safe dose and understand the drug's behavior in the body. The study will examine its effects on various cancers, including HER2-negative breast cancer with BRCA1 or BRCA2 deficiencies and hard-to-treat solid tumors. Individuals whose solid tumors have returned or spread after standard treatments might be suitable candidates, particularly if their cancer has specific genetic markers or characteristics. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in humans.

Will I have to stop taking my current medications?

The trial requires that you stop taking any other anti-cancer treatments and transition off strong or moderate CYP2C8 inhibitors or inducers (types of medications that affect how drugs are processed in the body).

Is there any evidence suggesting that ATX-559 is likely to be safe for humans?

Earlier research showed that ATX-559 held promise in lab tests for treating various types of cancer. These preclinical tests, conducted in labs using cells or animals, found that ATX-559 was well-tolerated, suggesting it might not cause severe side effects in humans. However, human trials are necessary to confirm this.

Currently, ATX-559 is undergoing a Phase 1 trial, the first step in testing a treatment in humans. Phase 1 trials primarily aim to determine the safest dose and assess how well people tolerate the treatment. As an early-stage trial, there is still limited information about human reactions to ATX-559. Reaching this phase indicates it passed initial safety tests in lab settings, and researchers believe it could be safe for human testing. Until more data emerges from ongoing studies, caution remains essential. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for cancer, which often include chemotherapy, radiation, and targeted therapies, ATX-559 is being explored for its potential to target specific genetic deficiencies and instability in tumors. Researchers are particularly excited because ATX-559 may provide a new way to treat cancers with BRCA1 or BRCA2 deficiencies and MSI-H/dMMR features. This precision approach could lead to more effective and personalized cancer therapies, offering new hope for patients who may not respond well to existing options.

What evidence suggests that ATX-559 might be an effective treatment for advanced solid tumors?

Research has shown that ATX-559, a new drug, may help treat certain cancers. In early lab studies, it proved very effective against various solid tumors, including those with specific genetic mutations called BRCA1 or BRCA2, often found in some breast cancers. This trial includes a dose expansion arm specifically for BRCA1- or BRCA2-deficient HER2-negative breast cancer. For tumors with high levels of genetic instability, known as MSI-H or dMMR, ATX-559 significantly slowed tumor growth in lab models. Another dose expansion arm in this trial focuses on MSI-H/dMMR solid tumors. These early research results offer a hopeful outlook for its potential use in humans. ^{1 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with advanced or metastatic solid tumors, including colorectal, endometrial, breast, colon, and rectal cancers. Participants should have specific molecular markers that make them suitable for treatment with ATX-559.

Inclusion Criteria

My cancer has returned or spread to other parts of my body.

For the expansion cohorts, participants must have histological confirmation of the specified tumor types: BRCA1 or BRCA2 deficient, HER2 negative metastatic breast cancer with no limit to the number of prior treatment regimens; dMMR or MSI-H with unresectable or metastatic solid tumors with 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

My condition did not improve after all standard treatments, or I cannot receive or refused them.

Exclusion Criteria

I am not receiving any other cancer treatments.

I do not have active or uncontrolled heart problems.

I do not have unstable brain tumors or metastasis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Subjects will be enrolled at various doses or schedules of ATX-559 to identify the recommended phase 2 dose (RP2D)

12 months

Dose Expansion

Participants with MSI-H/dMMR solid tumors and BRCA1- or BRCA2-deficient HER2-negative breast cancer will be enrolled to assess anti-tumor effect and further examine safety and PK of ATX-559 at the RP2D

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• ATX-559

Trial Overview The study tests the safety and appropriate dosage of a new oral medication called ATX-559 designed to inhibit DHX9. It also looks at how the body processes the drug and its preliminary effects on shrinking or controlling tumor growth.

How Is the Trial Designed?

Group I: Dose escalation Experimental Treatment 1 Intervention

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

Group II: Dose Expansion: MSI-H/dMMR solid tumors Experimental Treatment 1 Intervention

Group III: Dose Expansion: BRCA1- or BRCA2-deficient HER2-negative breast cancer Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Accent Therapeutics

Lead Sponsor

Trials

2

Recruited

170+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06625515

NCT06625515 | First-in-Human Study of ATX-559, an Oral ... First-in-Human Study of ATX-559, an Oral Inhibitor of DHX9, in Patients With Advanced or Metastatic Solid Tumors, and Molecularly Defined Cancers.

2. accenttx.com accenttx.com/news-events/accent-therapeutics-first-patient-dosed-phase-1-2-trial-atx-559-cso-transition/

Phase 1/2 study initiated for ATX-559, a first-in- ... The trial is enrolling solid tumor patients, with a particular focus on patients with BRCA1- or BRCA2-deficient breast cancer and patients with ...

3. accenttx.com accenttx.com/news-events/accent-therapeutics-announces-fda-clearance-of-ind-application-for-atx-559-a-first-in-class-oral-dhx9-inhibitor/

Accent Therapeutics Announces FDA Clearance of IND ... The ATX-559 Phase 1/2 trial (NCT06625515) is expected to begin dosing patients with a focus on BRCA1- or BRCA2-deficient breast cancer and ...

4. synapse.patsnap.com synapse.patsnap.com/article/fda-clears-ind-for-accent-therapeutics-oral-dhx9-inhibitor-atx-559

FDA Clears IND for Accent Therapeutics' Oral DHX9 ... ATX-559, a unique DHX9 inhibitor, is set to begin a Phase 1/2 clinical trial targeting patients with BRCA1/2-deficient breast cancer and various ...

5. delta.larvol.com delta.larvol.com/Products/?ProductId=daedf7dc-460f-468d-a30b-d3e6bea5a47c

ATX-559 / Accent Therap ATX-559, a first in class DHX9 inhibitor, and targeted therapeutic for molecularly defined tumors with genomic instability and replicative stress.

6. accenttx.com accenttx.com/news-events/accent-therapeutics-announces-trial-in-progress-poster-for-first-in-human-study-of-atx-559-at-2025-asco-annual-meeting/

ATX-559, a first-in-class oral DHX9 inhibitor ... Primary endpoints include identification of the recommended Phase 2 dose (RP2D) and assessment of the safety and tolerability of ATX-559.

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS3181

Trial in progress: First-in-human study of ATX-559, an oral ... 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 to determine the ...

8. aacrjournals.org aacrjournals.org/cancerres/article/85/8_Supplement_1/1758/757042/Abstract-1758-ATX-559-a-first-in-class-DHX9

Abstract 1758: ATX-559, a first in class DHX9 inhibitor, and ... ATX-559 is well tolerated in vivo across multiple cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models, when dosed ...

9. prnewswire.com prnewswire.com/news-releases/accent-therapeutics-presents-new-preclinical-data-on-lead-clinical-programs-atx-295-and-atx-559-at-the-2025-aacr-nci-eortc-international-conference-on-molecular-targets-and-cancer-therapeutics-302589136.html

Accent Therapeutics Presents New Preclinical Data on ... Summary: Preclinical data show the first-in-class oral DHX9 inhibitor, ATX-559, increases replicative stress and DNA damage, leading to ...