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

NCT06395519 | Recruiting Phase 1 FDA Drug

• 1 other identifier: ETX-19477-101
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 14

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

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

Keywords

PARG Inhibitor

Outcome Measures

Primary Outcomes (1)

• To characterize the safety and tolerability of ETX-19477, the maximum tolerated dose (MTD) and/or RP2D of ETX-19477

  Frequency of dose-limiting toxicities (DLTs), frequency and severity of AEs, including abnormal ECG parameters, and serious adverse events (SAEs)

  6 months

Secondary Outcomes (7)

• To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring maximum plasma concentration (Cmax)

  3 months

• To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring maximum blood concentration (tmax)

  3 months

• To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring elimination half-life (t1/2)

  3 months

• To further characterize the pharmacokinetic (PK) profile of ETX-19477 by the Area Under the Blood Concentration-Time Curve (AUC0-t, AUC0-inf), Clearance (CL), Volume of Distribution (Vd)

  3 months

• To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring objective response rate (ORR) using RECIST v1.1

  2 years

Study Arms (2)

Phase 1 Part 1: Monotherapy Dose Escalation

EXPERIMENTAL

Participants will be assigned to a dose level.

Drug: ETX-19477

Phase 1 Part 2: Monotherapy Dose Expansion

EXPERIMENTAL

After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.

Drug: ETX-19477

Interventions

ETX-19477 DRUG

Oral medication taken daily

Phase 1 Part 1: Monotherapy Dose Escalation; Phase 1 Part 2: Monotherapy Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.
• 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

Sponsors & Collaborators

• 858 Therapeutics, Inc.: lead

Study Sites (14)

Mayo Clinic

Phoenix, Arizona, 85054, United States

RECRUITING

Yale University, Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

Mayo Clinic

Jacksonville, Florida, 32224, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Stefanie Spielman Comprehensive Breast Center

Columbus, Ohio, 43212, United States

RECRUITING

Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START Center for Cancer Care - Mountain Region

Salt Lake City, Utah, 84112, United States

RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Ovarian Neoplasms; Prostatic Neoplasms; Carcinoma, Ovarian Epithelial; Endometrial Neoplasms; Colorectal Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Genital Neoplasms, Male; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Uterine Neoplasms; Uterine Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases

Study Officials

• Daniel McCormick

  858 Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

858 Therapeutics, Inc.

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: May 2, 2024
• Study Start: May 13, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 27, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (14)