Actively Recruiting
A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
Led by 858 Therapeutics, Inc. · Updated on 2026-03-27
120
Participants Needed
14
Research Sites
N/A
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating ETX-19477, a novel reversible small molecule inhibitor of poly (ADP) ribose glycohydrolase (PARG), in patients with advanced solid tumors. This two-part, open-label, multicenter study aims to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary anti-tumor activity of ETX-19477. The study focuses on tumors characterized by replication stress and DNA damage response pathways, targeting a vulnerability in cancer cells. The study includes two parts: Part 1 involves dose escalation where participants receive daily oral doses of ETX-19477 to determine the maximum tolerated dose or recommended phase 2 dose. Part 2 is a dose expansion phase where participants receive the determined dose level. Participants are assigned to a dose level in each part. The study does not use placebo and is non-randomized. Participants will undergo assessments to monitor safety and side effects, as well as pharmacokinetic measurements of the drug concentration in the blood over time. Researchers will also evaluate tumor responses using standardized criteria over up to two years. The primary outcome is safety and tolerability measured over six months. Additional evaluations include pharmacokinetic profiles at three months and anti-tumor activity measures such as response rates and disease control over two years. The study is expected to continue until December 2026.
CONDITIONS
Brief Title
A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Males and females aged 18 years or older at the time of consent
- Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer excluding primary central nervous system tumors
- Solid tumor malignancy with progression on or after or intolerance to most recent systemic therapy
- Preferential enrollment for patients with known BRCA2 mutations causing loss of function
- Measurable disease per RECIST v1.1 criteria
- ECOG performance status of 0 or 1
- Prior treatment in recurrent/metastatic setting with approved standard therapy unless contraindicated or declined
- No investigational agent within 3 weeks or 5 half-lives prior to first dose
- Life expectancy of at least 3 months
You will not qualify if you...
- Receiving continuous corticosteroids at prednisone-equivalent dose greater than 10 mg/day
- Definitive radiotherapy within 6 weeks or palliative radiation within 2 weeks prior to first dose
- Symptomatic untreated or progressing brain metastases; stable treated brain metastases allowed if no progression or increased corticosteroid use for 4 weeks
- Gastrointestinal impairment or disease affecting drug absorption; no bowel obstruction within 6 months or peritoneal fluid drainage within 8 weeks prior to first dose
- Known symptomatic and radiologically progressing leptomeningeal disease unless no neurological symptoms
- Resting ECG with QTcF greater than 470 msec on 2 or more timepoints or history/family history of long QT syndrome or risk factors
- Recent myocardial infarction or unstable angina within 6 months or significant cardiac disease
- Known active or chronic infections including tuberculosis, hepatitis B, hepatitis C, or AIDS-related illness unless controlled
- Acute or chronic uncontrolled renal, pancreatic, or liver disease except specified exceptions
- Other previous or current malignancy requiring treatment within 2 years except limited curatively treated conditions
- Use of proton pump inhibitors within 7 days prior to first dose or strong CYP3A or P-gp inhibitors/inducers within 6 half-lives prior to first dose
- Current treatment with therapeutic doses of warfarin or other coumarin-derivative anticoagulants
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Up to 6 months
Participants receive daily oral doses of the study drug ETX-19477 to assess safety, tolerability, and preliminary anti-tumor activity.
Regular visits for dosing and assessments as per protocol
Duration - Up to 2 years
Participants are monitored after treatment ends to assess safety and long-term treatment effects.
Periodic visits for up to 2 years
Trial Site Locations
Total: 14 locations
1
Mayo Clinic
Phoenix, Arizona, United States, 85054
Actively Recruiting
2
Yale University, Yale Cancer Center
New Haven, Connecticut, United States, 06510
Actively Recruiting
3
Mayo Clinic
Jacksonville, Florida, United States, 32224
Actively Recruiting
4
University of Chicago Medical Center
Chicago, Illinois, United States, 60637
Actively Recruiting
5
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Actively Recruiting
6
Mayo Clinic
Rochester, Minnesota, United States, 55905
Actively Recruiting
7
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, United States, 10016
Actively Recruiting
8
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Actively Recruiting
9
Stefanie Spielman Comprehensive Breast Center
Columbus, Ohio, United States, 43212
Actively Recruiting
10
Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center
Philadelphia, Pennsylvania, United States, 19107
Actively Recruiting
11
MD Anderson Cancer Center
Houston, Texas, United States, 77030
Actively Recruiting
12
START Center for Cancer Care - Mountain Region
Salt Lake City, Utah, United States, 84112
Actively Recruiting
13
Virginia Cancer Specialists
Fairfax, Virginia, United States, 22031
Actively Recruiting
14
Fred Hutchinson Cancer Center
Seattle, Washington, United States, 98109
Actively Recruiting
Research Team
8
858 Therapeutics, Inc.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here