Advanced Solid TumorsPhase 1NCT06625515
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 study testing ATX-559 in people with Advanced Solid Tumors and Breast Cancer Recurrent, run by Accent Therapeutics at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Solid Tumors, Breast Cancer Recurrent, Colorectal Cancer Metastatic
- What is being tested?
- ATX-559
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 5 sitesUnited States
- Study dates
- 11 Oct 2024to 9 Jan 2026
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Colorado Cancer Center - Anschutz Medical Campus,
Aurora, Colorado, 80045
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
SCRI Oncology Partners
Nashville, Tennessee, 37203
Stephenson Cancer Center at OU Medicine
Oklahoma City, Oklahoma, 73104
NEXT Oncology
San Antonio, Texas, 78229
About this study
Official title: 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
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.
Read the 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
- Being tested
- ATX-559
- Keywords
- MSI-high/dMMR tumors, BRCA1 mutation, BRCA2 mutation, DHX9, dMMR, deficient mismatch repair, microsatellite instability
- Medical subject headings
- Colonic Neoplasms, Rectal Neoplasms, Endometrial Neoplasms, Microsatellite Instability
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATX-559Drug
DHX9 tablets will be taken orally
| Study group | Role | What they receive |
|---|---|---|
| Dose escalation | Experimental | Subjects will be enrolled at various doses or schedules of ATX-559 to identify the RP2D Receives: Drug: ATX-559 |
| Dose Expansion: MSI-H/dMMR solid tumors | Experimental | Not described Receives: Drug: ATX-559 |
| Dose Expansion: BRCA1- or BRCA2-deficient HER2-negative breast cancer | Experimental | Not described Receives: Drug: ATX-559 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 12 months
Safety and tolerability of ATX-559
Incidence of adverse events graded according to CTCAE v5.0
Measured: 12 months
Secondary outcomes (5)
Preliminary evidence of antitumor activity
Objective response rate based on RECIST v1.1
Measured: 12 months
Pharmacodynamic activity of ATX-559 in blood over time via measurement of circBRIP1 RNA levels
Measured: 12 months
Maximum observed plasma concentration of ATX-559 (Cmax)
Measured: 12 months
Calculated time to reach maximum observed plasma concentration (Tmax)
Measured: 12 months
Calculated area under the plasma concentration-time curve of ATX-559 (AUC0-t)
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Oct 2024
- Study start11 Oct 2024
- Primary completion9 Jan 2026
- Study completion9 Jan 2026
Why it stopped: The study was terminated by sponsor based on the adverse event profile.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Accent Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06625515
- Sponsor's protocol ID
- ATX-559-001
- Status last verified
- Feb 2026
- First submitted
- 23 Sep 2024
- Last updated
- 24 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06625515
- Acronym / sponsor ID
- ATX-559-001
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated by sponsor based on the adverse event profile.
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Accent TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 11 Oct 2024 (actual)
- Primary completion
- 9 Jan 2026 (actual)
- Study completion
- 9 Jan 2026 (actual)
- First posted
- 3 Oct 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Dose escalation | Experimental | Drug: ATX-559Subjects will be enrolled at various doses or schedules of ATX-559 to identify the RP2D |
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATX-559DHX9 tablets will be taken orally | Drug | Dose Expansion: BRCA1- or BRCA2-deficient HER2-negative breast cancer, Dose Expansion: MSI-H/dMMR solid tumors, Dose escalation |
Primary outcome
Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-559
Time frame: 12 months
Identification of a tolerable and safe dose for expansion cohorts based on dose limiting toxicities
Safety and tolerability of ATX-559
Time frame: 12 months
Incidence of adverse events graded according to CTCAE v5.0
5 secondary outcomes
Preliminary evidence of antitumor activity
Time frame: 12 months
Pharmacodynamic activity of ATX-559 in blood over time via measurement of circBRIP1 RNA levels
Time frame: 12 months
Maximum observed plasma concentration of ATX-559 (Cmax)
Time frame: 12 months
Calculated time to reach maximum observed plasma concentration (Tmax)
Time frame: 12 months
Calculated area under the plasma concentration-time curve of ATX-559 (AUC0-t)
Time frame: 12 months
Results and safety
The study was stopped early (reason given: The study was terminated by sponsor based on the adverse event profile.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing ATX-559 in people with Advanced Solid Tumors and Breast Cancer Recurrent, run by Accent Therapeutics at 5 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 24 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The study was terminated by sponsor based on the adverse event profile.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recommended phase 2 dose (RP2D) and/or maximum tolerated dose (MTD) of ATX-559 (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Feb 2026.