RecruitingPhase 1 / Phase 2

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

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
18 Years and older
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This study tests ETX-19477, a drug that blocks a protein called PARG, in adults with advanced solid cancers. It looks at the drug’s safety, how it works in the body, and whether it fights cancer.

This is a two-part, open-label, multicenter, dose escalation and dose expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PDx), and anti- tumor activity of ETX-19477, a novel reversible small molecule inhibitor of PARG.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • You must be at least 18 years old.
  • Tests must confirm a solid cancer that has come back and cannot be cured, cannot be removed by surgery, or has spread. Cancers that started in the brain or spinal cord are not included.
  • Your cancer must have worsened during or after your latest whole-body cancer treatment, or you could not tolerate that treatment. People with certain BRCA2 gene changes may get priority.
  • You must have received available standard treatment for cancer that came back or spread, unless it was unsafe, caused side effects you could not tolerate, or you declined it.
  • Your cancer must be measurable using the study’s rules.
  • You must be fully active or able to do light work despite limits on hard physical activity.
  • You must stop other experimental drugs before starting. The required wait depends on how long the drug stays in your body, but is at least 2 weeks.
  • You must be expected to live at least 3 months.

Who can't join

  • Daily steroid treatment above a dose equal to 10 mg of prednisone. Lower-dose replacement steroids and steroids used in places such as the skin or lungs are allowed.
  • Radiation meant to treat the cancer within 6 weeks, or radiation to ease symptoms within 2 weeks, before starting the study drug.
  • Brain cancer spread that is untreated and causes symptoms, or is getting worse. Treated brain spread may be allowed if stable for at least 4 weeks without increased steroid use. Cancer in the lining around the brain or spinal cord also has restrictions.
  • Gut problems that could greatly affect how your body takes in the drug, or uncontrolled kidney disease, swelling of the pancreas, or liver disease. Some liver conditions are allowed.
  • Certain heart rhythm risks, serious heart disease, or a heart attack or unstable chest pain within 6 months. Uncontrolled high blood pressure or any past heart failure with symptoms also excludes you.
  • An active or long-term infection, including tuberculosis, hepatitis B or C, or AIDS-related illness. Some controlled infections, including HIV and cured hepatitis C, may be allowed.
  • Another cancer needing treatment within the past 2 years. Some limited cancers treated with the aim of curing them are allowed if ongoing chemotherapy is not needed.
  • Use of certain acid-reducing drugs called PPIs, medicines that affect how the study drug is handled by the body, or warfarin or similar blood thinners at treatment doses. Some medicines must be stopped before starting.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility 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

Study sites (14)

AZ

CT

  • Yale University, Yale Cancer Center · New Haven, CT 06510Michael Cecchini, MD · Principal investigatorMore trials in New Haven

FL

IL

  • University of Chicago Medical Center · Chicago, IL 60637Han Cun, MD · Principal investigatorMore trials in Chicago

MA

  • Massachusetts General Hospital · Boston, MA 02114Richard T Penson, MD · Principal investigatorMore trials in Boston

MN

NY

  • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health · New York, NY 10016Nancy Chan, MD · Principal investigatorMore trials in New York
  • Memorial Sloan Kettering Cancer Center · New York, NY 10065Ezra Y Rosen, MD, PhD · Principal investigatorMore trials in New York

OH

  • Stefanie Spielman Comprehensive Breast Center · Columbus, OH 43212Sagar Sardesai, MBBS · Principal investigatorMore trials in Columbus

PA

  • Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center · Philadelphia, PA 19107Kevin Zarrabi, MD · Principal investigatorMore trials in Philadelphia

TX

  • MD Anderson Cancer Center · Houston, TX 77030Timothy A Yap, MD, PhD · Principal investigatorMore trials in Houston

UT

  • START Center for Cancer Care - Mountain Region · Salt Lake City, UT 84112William B. McKean, Jr, MD · Principal investigatorMore trials in Salt Lake City

VA

  • Virginia Cancer Specialists · Fairfax, VA 22031Alexander I Spira, MD · Principal investigatorMore trials in Fairfax

WA

  • Fred Hutchinson Cancer Center · Seattle, WA 98109Kalyan Banda, MD · Principal investigatorMore trials in Seattle