Recruiting
Phase 1
Phase 2

ETX-19477

Sponsor:

858 Therapeutics, Inc.

Code:

NCT06395519

Conditions

Advanced or Metastatic Solid Tumors

Breast Cancer

Ovarian Cancer

Prostate Cancer

Epithelial Ovarian Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

ETX-19477

Study Details

Brief summary:

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.

Conditions

Advanced or Metastatic Solid Tumors

Breast Cancer

Ovarian Cancer

Prostate Cancer

Epithelial Ovarian Cancer

Study ID

NCT06395519

Start date

May 13, 2024

Status verified date

Mar, 2026

Completion date

Dec, 2026

Anticipated

Primary completion date

Dec, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

120 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1 Part 1: Monotherapy Dose Escalation

Participants will be assigned to a dose level.

experimental: 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.

Interventions

ETX-19477

Oral medication taken daily

Primary outcome measure

  • To characterize the safety and tolerability of ETX-19477, the maximum tolerated dose (MTD) and/or RP2D of ETX-19477 [ Time Frame: 6 months ]

Central Contacts and Locations

Central contacts

858 Therapeutics, Inc.

(858) 987-8380dmccormick@8five8tx.com

Locations

Mayo Clinic

Recruiting

Phoenix, Arizona, United States, 85054

Principal Investigator:

Felipe Batalini, MD

Yale University, Yale Cancer Center

Recruiting

New Haven, Connecticut, United States, 06510

Principal Investigator:

Michael Cecchini, MD

Mayo Clinic

Recruiting

Jacksonville, Florida, United States, 32224

Principal Investigator:

Pooja Advani, MD

University of Chicago Medical Center

Recruiting

Chicago, Illinois, United States, 60637

Principal Investigator:

Han Cun, MD

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Principal Investigator:

Richard T Penson, MD

Mayo Clinic

Recruiting

Rochester, Minnesota, United States, 55905

Principal Investigator:

Siddhartha Yadav, MD

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

Recruiting

New York, New York, United States, 10016

Principal Investigator:

Nancy Chan, MD

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Principal Investigator:

Ezra Y Rosen, MD, PhD

Stefanie Spielman Comprehensive Breast Center

Recruiting

Columbus, Ohio, United States, 43212

Principal Investigator:

Sagar Sardesai, MBBS

Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center

Recruiting

Philadelphia, Pennsylvania, United States, 19107

Principal Investigator:

Kevin Zarrabi, MD

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

Principal Investigator:

Timothy A Yap, MD, PhD

START Center for Cancer Care - Mountain Region

Recruiting

Salt Lake City, Utah, United States, 84112

Principal Investigator:

William B. McKean, Jr, MD

Virginia Cancer Specialists

Recruiting

Fairfax, Virginia, United States, 22031

Principal Investigator:

Alexander I Spira, MD

Fred Hutchinson Cancer Center

Recruiting

Seattle, Washington, United States, 98109

Principal Investigator:

Kalyan Banda, MD

More Information

Sponsor

858 Therapeutics, Inc.

Last update posted

Mar 27, 2026

Last verified

Mar, 2026

Keywords

  • PARG Inhibitor

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by 858 Therapeutics, Inc. on 2026-03-27.