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Testing a new drug ETX-19477 for advanced solid tumors

A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies

Phase1; Phase2 Interventional 858 Therapeutics, Inc. · NCT06395519

This study is testing a new drug called ETX-19477 to see if it can help people with advanced solid tumors that haven't responded to other treatments.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
Sponsor858 Therapeutics, Inc. Industry-sponsored
Drugs / interventionschemotherapy, radiation, prednisone
Locations14 sites (Phoenix, Arizona and 13 other locations)
Trial IDNCT06395519 on ClinicalTrials.gov

What this trial studies

This is a two-part, open-label study designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and anti-tumor activity of ETX-19477, a novel reversible small molecule inhibitor of PARG. The study focuses on patients with advanced or metastatic solid tumors who have shown progression on or intolerance to previous therapies. It aims to exploit the cancer-specific vulnerability associated with replication stress by targeting PARG inhibition to potentially enhance tumor response. The study will involve dose escalation and expansion phases to determine the optimal dosing regimen.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with advanced solid tumors who have progressed on or are intolerant to previous systemic therapies.

Not a fit: Patients with primary central nervous system tumors or those who have received investigational agents within the specified timeframe may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that are resistant to standard therapies.

How similar studies have performed: While this approach is novel in targeting PARG inhibition specifically, similar studies targeting DNA damage response pathways have shown promise in cancer treatment.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* Males and females of age ≥ 18 years at the time of signing the informed consent document.
* Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer, excluding primary central nervous system (CNS) tumors.
* Any solid tumor malignancy, excluding primary CNS tumors, with progression on or after or intolerance to most recent systemic therapy. Preferential enrollment consideration will be made for patients with known BRCA2 mutations resulting in loss of function.
* Measurable disease per RECIST v1.1.
* ECOG performance status 0-1.
* Progression on or after or intolerance to most recent systemic therapy. Prior treatment in the recurrent/metastatic setting; patients must have received approved standard therapy that is available to the patient that is known to confer clinical benefit, unless this therapy is contraindicated, intolerable to the patient, or is declined by the patient.
* No investigational agent within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug.
* Life expectancy of at least 3 months.

Exclusion Criteria:

* Receiving continuous corticosteroids at prednisone-equivalent dose of \>10 mg/day. Chronic systemic corticosteroid therapy for physiologic replacement (≤10 mg/day of prednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled, topical, intra-nasal, intra-articular, or ophthalmic) are permitted.
* Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug.
* Symptomatic untreated or progressing brain metastases. Stable, treated brain metastases are allowed if no evidence of radiologic or clinical progression or increasing corticosteroid use for at least 4 weeks.
* Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of ETX-19477 and no history of bowel obstruction within 6 months and/or peritoneal fluid drainage within 8 weeks prior to the first dose of study drug.
* Known symptomatic and radiologically progressing or leptomeningeal disease (LMD). If LMD has been reported radiographically on baseline magnetic resonance imaging (MRI), but is not suspected clinically by the Investigator, the patient must be free of neurological symptoms of LMD.
* Resting ECG with QT interval calculated using the Fridericia's formula (QTcF) \>470 msec on 2 or more timepoints within a 24-hour period, or history or family history of congenital long QT syndrome, or taking concomitant medications that are known to prolong the QT/QTc interval, or history of additional risk factors for torsades de pointes (Tdp).
* History of myocardial infarction or unstable angina within 6 months prior to enrollment, or clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension, clinically significant uncontrolled arrhythmias, or any history of symptomatic congestive heart failure.
* Known active or chronic infection (viral, bacterial, or fungal), including tuberculosis, hepatitis B, hepatitis C, or AIDS-related illness. Controlled infections, including HIV and "cured" hepatitis C (no active fever, no evidence of systemic inflammatory response syndrome) that are stable with undetectable viral load on antiviral treatment are not exclusionary.
* Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (with exception of patients with Gilbert's Syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per Investigator assessment).
* Known other previous/current malignancy requiring treatment within ≤2 years except for limited disease treated with curative intent, such as carcinoma in situ, squamous or basal cell skin carcinoma, or superficial bladder carcinoma and not requiring ongoing chemotherapy.
* Patients receiving proton pump inhibitors (PPIs), strong cytochrome P450 (CYP)3A inhibitors and inducers, or P-glycoprotein (P-gp) inhibitors. Patients should not receive PPIs within 7 days prior to first dose of study drug. Strong CYP3A inducers or inhibitors or strong P-gp inhibitors should not be given within 6 half-lives prior to first dose of study drug.
* Patients currently treated with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants

Where this trial is running

Phoenix, Arizona and 13 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
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Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.