A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
NCT ID: NCT06395519
Last Updated: 2025-08-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
120 participants
INTERVENTIONAL
2024-05-13
2026-12-31
Brief Summary
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Detailed Description
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Poly (ADP) ribose glycohydrolase (PARG) plays a critical role in DDR with genetic depletion or inhibition by reference compounds resulting in increased numbers of single-strand breaks (SSBs) and double-strand breaks (DSBs) and reduced kinetics of break repair. In addition, under conditions of replication stress in cancer cells, PARG depletion or inhibition has been shown to inhibit proliferation and arrest cells in the S or G2 phase of the cell cycle and/or induce apoptosis alone or in combination with DNA damaging agents or replication stress inducers. The replication stress response represents a cancer-specific vulnerability, which can be targeted by PARG small molecule inhibition.
Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Phase 1 Part 1: Monotherapy Dose Escalation
Participants will be assigned to a dose level.
ETX-19477
Oral medication taken daily
Phase 1 Part 2: Monotherapy Dose Expansion
After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.
ETX-19477
Oral medication taken daily
Interventions
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ETX-19477
Oral medication taken daily
Eligibility Criteria
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Inclusion Criteria
* 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.
* 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
* 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 prior to enrollment.
* 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.
* 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.
* 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
18 Years
ALL
No
Sponsors
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858 Therapeutics, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Daniel McCormick
Role: STUDY_DIRECTOR
858 Therapeutics, Inc.
Locations
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Mayo Clinic
Phoenix, Arizona, United States
Yale University, Yale Cancer Center
New Haven, Connecticut, United States
Mayo Clinic
Jacksonville, Florida, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center
Philadelphia, Pennsylvania, United States
MD Anderson Cancer Center
Houston, Texas, United States
START Center for Cancer Care - Mountain Region
Salt Lake City, Utah, United States
Virginia Cancer Specialists
Fairfax, Virginia, United States
Fred Hutchinson Cancer Center
Seattle, Washington, United States
Countries
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Central Contacts
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Other Identifiers
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ETX-19477-101
Identifier Type: -
Identifier Source: org_study_id
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