Informations générales (source: ClinicalTrials.gov)
A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
Interventional
Phase 1/Phase 2
858 Therapeutics, Inc. (Voir sur ClinicalTrials)
mai 2024
décembre 2026
11 août 2026
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.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Kaissa OUALI | 31/08/2026 14:25:02 | Contacter | ||
Critères
Tous
- 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