Advanced or Metastatic Solid TumorsPhase 1/2ERADIC8NCT06395519
A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
A Phase 1/2 study testing ETX-19477 in people with Advanced or Metastatic Solid Tumors and Breast Cancer, run by 858 Therapeutics, Inc. at 14 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer
- What is being tested?
- ETX-19477
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 14 sitesUnited States
- Study dates
- 13 May 2024to Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
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- 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
Trial locations and contacts
14 sites in 1 country. Contact the study team or a site near you to ask about taking part.
14 sites in 1 country
United States14 sites, 14 recruiting
- Recruiting
Massachusetts General Hospital
Boston, Massachusetts, 02114
Richard T Penson, MD
- Recruiting
University of Chicago Medical Center
Chicago, Illinois, 60637
Han Cun, MD
- Recruiting
Stefanie Spielman Comprehensive Breast Center
Columbus, Ohio, 43212
Sagar Sardesai, MBBS
- Recruiting
Virginia Cancer Specialists
Fairfax, Virginia, 22031
Alexander I Spira, MD
- Recruiting
MD Anderson Cancer Center
Houston, Texas, 77030
Timothy A Yap, MD, PhD
- Recruiting
Mayo Clinic
Jacksonville, Florida, 32224
Pooja Advani, MD
- Recruiting
Yale University, Yale Cancer Center
New Haven, Connecticut, 06510
Michael Cecchini, MD
- Recruiting
Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
New York, New York, 10016
Nancy Chan, MD
- Recruiting
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Ezra Y Rosen, MD, PhD
- Recruiting
Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center
Philadelphia, Pennsylvania, 19107
Kevin Zarrabi, MD
- Recruiting
Mayo Clinic
Phoenix, Arizona, 85054
Felipe Batalini, MD
- Recruiting
Mayo Clinic
Rochester, Minnesota, 55905
Siddhartha Yadav, MD
- Recruiting
START Center for Cancer Care - Mountain Region
Salt Lake City, Utah, 84112
William B. McKean, Jr, MD
- Recruiting
Fred Hutchinson Cancer Center
Seattle, Washington, 98109
Kalyan Banda, MD
About this study
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.
Read the detailed description
A hallmark of many cancer cells is replication stress, which is characterized by the slowing or stalling of replication forks during the DNA replication process, leading to the accumulation of damaged DNA. The cellular response to replication stress is the activation of cell-cycle checkpoints and the DNA damage response (DDR) pathway to arrest the cell cycle and promote repair of the damaged DNA.
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
- Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Prostate Cancer, Epithelial Ovarian Cancer, BRCA2 Mutation
- Being tested
- ETX-19477
- Keywords
- PARG Inhibitor
- Medical subject headings
- Breast Neoplasms, Ovarian Neoplasms, Prostatic Neoplasms, Carcinoma, Ovarian Epithelial, Endometrial Neoplasms, Colorectal Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ETX-19477Drug
Oral medication taken daily
| Study group | Role | What they receive |
|---|---|---|
| Phase 1 Part 1: Monotherapy Dose Escalation | Experimental | Participants will be assigned to a dose level. Receives: 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. Receives: Drug: ETX-19477 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 6 months
Secondary outcomes (7)
To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring maximum plasma concentration (Cmax)
Maximum Plasma Concentration [Cmax] for single (Cycle 1 Day 1) dose and at steady state (Cycle 2 Day 1) with trough levels at the beginning of the next cycle (Cycle 3 Day 1).
Measured: 3 months
To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring maximum blood concentration (tmax)
Time of Maximum Blood Concentration (tmax) for single dose and at steady state with trough levels at the beginning of the next cycle.
Measured: 3 months
To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring elimination half-life (t1/2)
Elimination half-life (t1/2) for single dose and at steady state with trough levels at the beginning of the next cycle.
Measured: 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)
Area Under the Blood Concentration-Time Curve (AUC0-t, AUC0-inf), Clearance (CL), Volume of Distribution (Vd) of ETX-19477
Measured: 3 months
To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring objective response rate (ORR) using RECIST v1.1
Objective response rate (ORR) assessed using RECIST criteria v1.1
Measured: 2 years
To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring duration of response (DOR) using RECIST v1.1
Duration of response (DOR) assessed using RECIST criteria v1.1
Measured: 2 years
To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring disease control rate (DCR) using RECIST v1.1
Disease control rate (DCR) assessed using RECIST criteria v1.1
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2024
- Study start13 May 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- 858 Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Daniel McCormick, Study director, 858 Therapeutics, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06395519
- Sponsor's protocol ID
- ETX-19477-101
- Acronym
- ERADIC8
- Status last verified
- Mar 2026
- First submitted
- 24 Apr 2024
- Last updated
- 27 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
- ClinicalTrials.gov ID
- NCT06395519
- Acronym / sponsor ID
- ERADIC8 / ETX-19477-101
- Conditions
- Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Prostate Cancer, Epithelial Ovarian Cancer, BRCA2 Mutation
- Keywords
- PARG Inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- 858 Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 13 May 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 2 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
A hallmark of many cancer cells is replication stress, which is characterized by the slowing or stalling of replication forks during the DNA replication process, leading to the accumulation of damaged DNA. The cellular response to replication stress is the activation of cell-cycle checkpoints and the DNA damage response (DDR) pathway to arrest the cell cycle and promote repair of the damaged DNA.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Phase 1 Part 1: Monotherapy Dose Escalation | Experimental | Drug: ETX-19477Participants will be assigned to a dose level. |
| Phase 1 Part 2: Monotherapy Dose Expansion | Experimental | Drug: ETX-19477After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ETX-19477Oral medication taken daily | Drug | Phase 1 Part 1: Monotherapy Dose Escalation, Phase 1 Part 2: Monotherapy Dose Expansion |
Primary outcome
To characterize the safety and tolerability of ETX-19477, the maximum tolerated dose (MTD) and/or RP2D of ETX-19477
Time frame: 6 months
Frequency of dose-limiting toxicities (DLTs), frequency and severity of AEs, including abnormal ECG parameters, and serious adverse events (SAEs)
7 secondary outcomes
To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring maximum plasma concentration (Cmax)
Time frame: 3 months
To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring maximum blood concentration (tmax)
Time frame: 3 months
To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring elimination half-life (t1/2)
Time frame: 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)
Time frame: 3 months
To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring objective response rate (ORR) using RECIST v1.1
Time frame: 2 years
To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring duration of response (DOR) using RECIST v1.1
Time frame: 2 years
To assess the preliminary anti-tumor activity of ETX-19477 in participants by measuring disease control rate (DCR) using RECIST v1.1
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Daniel McCormick study director
858 Therapeutics, Inc.
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ETX-19477 in people with Advanced or Metastatic Solid Tumors and Breast Cancer, run by 858 Therapeutics, Inc. at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 27 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact 858 Therapeutics, Inc. ((858) 987-8380, dmccormick@8five8tx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2026.