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

Recruiting now · Phase 1/Phase 2

Conditions studied: Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Prostate Cancer, Epithelial Ovarian Cancer, BRCA2 Mutation, ER+ Breast Cancer, Castrate Resistant Prostate Cancer, BRCA1 Mutation, BRCA Mutation, Endometrial Cancer, Colorectal Cancer, Gastric Cancer

In brief

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.

Key facts

Study ID

NCT06395519

Run by

858 Therapeutics, Inc.

People needed

120

Starts

2024-05-13

Expected to finish

2026-12-01

Last updated by the study team

2026-03-27

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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.

You may not qualify if…

• 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 it is running

• Mayo Clinic — Phoenix, Arizona, United States (enrolling)
• Yale University, Yale Cancer Center — New Haven, Connecticut, United States (enrolling)
• Mayo Clinic — Jacksonville, Florida, United States (enrolling)
• University of Chicago Medical Center — Chicago, Illinois, United States (enrolling)
• Massachusetts General Hospital — Boston, Massachusetts, United States (enrolling)
• Mayo Clinic — Rochester, Minnesota, United States (enrolling)
• Laura & Isaac Perlmutter Cancer Center at NYU Langone Health — New York, New York, United States (enrolling)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (enrolling)
• Stefanie Spielman Comprehensive Breast Center — Columbus, Ohio, United States (enrolling)
• Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center — Philadelphia, Pennsylvania, United States (enrolling)
• MD Anderson Cancer Center — Houston, Texas, United States (enrolling)
• START Center for Cancer Care - Mountain Region — Salt Lake City, Utah, United States (enrolling)
• Virginia Cancer Specialists — Fairfax, Virginia, United States (enrolling)
• Fred Hutchinson Cancer Center — Seattle, Washington, United States (enrolling)

Full record on ClinicalTrials.gov

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