Authorised Phase I and Phase II (Integrated)- First administration to humans Patients with advanced solid malignancies that have progressed following standard therapy

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

EU CTIS ID: 2024-518326-32-00

What this study is testing

Phase 1: - To determine the maximum tolerated dose (MTD) and/or RD of ETX-19477 - To characterize the safety and tolerability of ETX-19477 Phase 2a: -To assess the anti-tumor activity of ETX-19477 using RECIST v1.1

Phase I and Phase II (Integrated)- First administration to humans

A plain-language read of the study's public EU CTIS listing. The study team confirms the details.

Who can take part

You may be able to join if

1.) Males and females of age ≥18 years at the time of signing the informed consent document.
4.) 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. The reason for treatment decline must be clearly documented in the medical record and Sponsor Medical Monitor approval obtained.
6.) Measurable disease per RECIST v1.1.
7.) ECOG performance status 0–1.
8.) Life expectancy of at least 3 months.
9.) Willing to provide a pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy [preferably from a progressing lesion and preferably obtained during or after disease progression on last regimen received]). Patients without available archival tissue and/or where biopsy is not considered safe and/or medically feasible may be enrolled with approval of the Sponsor Medical Monitor.

You likely can't join if

1.) 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.
5.) Impairment of GI function or GI disease that may significantly alter the absorption of ETX 19477. No history of bowel obstruction within 6 months and/or peritoneal fluid drainage within 8 weeks prior to the first dose of study drug.
6.) Known symptomatic and radiologically progressing or LMD. If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator, the patient must be free of neurological symptoms of LMD.
7.) Resting ECG with QTcF >470 msec on 2 or more timepoints within a 24-hour period, or history or family history of congenital long QT syndrome
8.) 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.
9.) 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.

See the full eligibility criteria

Who can join

1.) Males and females of age ≥18 years at the time of signing the informed consent document.
4.) 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. The reason for treatment decline must be clearly documented in the medical record and Sponsor Medical Monitor approval obtained.
6.) Measurable disease per RECIST v1.1.
7.) ECOG performance status 0–1.
8.) Life expectancy of at least 3 months.
9.) Willing to provide a pretreatment tumor sample (either an archival sample or a sample obtained by pretreatment biopsy [preferably from a progressing lesion and preferably obtained during or after disease progression on last regimen received]). Patients without available archival tissue and/or where biopsy is not considered safe and/or medically feasible may be enrolled with approval of the Sponsor Medical Monitor.
10.) All adverse events resulting from prior cancer therapies must have resolved to NCI CTCAE v5.0 Grade ≤1 or pre-therapy baseline with the exception of alopecia or ≤ Grade 2 neuropathy (except for laboratory parameters outlined below).
11.) Adequate hematological, renal, and hepatic function: a) ANC ≥1.5×109/L (no GCSF within 14 days of study enrollment) b) Platelet count ≥100×109/L (no platelet transfusions within 7 days of study enrollment) c) Hemoglobin ≥10.0 g/dL (no RBC transfusions within 14 days of study enrollment) d) Albumin >3.0 g/dL e) ALT ≤3×ULN (if liver metastases are present, ≤5.0×ULN) f) AST ≤3×ULN (if liver metastases are present, ≤5.0×ULN) g) Total bilirubin ≤1.5×ULN (patients with known Gilbert’s Syndrome may enroll with 2.5×ULN provided the direct bilirubin is ≤1.5 mg/dL) h) Calculated estimated glomerular filtration rate of ≥50 mL/minute/1.73m2 by CKD-EPI equation i) PT and/or INR and PTT or aPTT ≤1.5×ULN
12.) No investigational agent within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug
13.) Female patients of childbearing potential must agree to use highly effective contraception or abstinence during the period of therapy and in the following 90 days after discontinuation of study treatment. Male patients must be surgically sterile or abstinent or both the male and their female partners of childbearing potential must agree to use highly effective contraception with supplementary barrier method (male condom) during the period of therapy and in the following 90 days after discontinuation of study treatment.
14.) Able to swallow an oral medication.
15.) Willing and able to adhere to the study visit schedule and other protocol requirements.
2.) Able to understand and voluntarily sign an informed consent document prior to any study-related assessments/procedures.
3.) Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer, excluding primary CNS tumors.

What rules you out

1.) 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.
5.) Impairment of GI function or GI disease that may significantly alter the absorption of ETX 19477. No history of bowel obstruction within 6 months and/or peritoneal fluid drainage within 8 weeks prior to the first dose of study drug.
6.) Known symptomatic and radiologically progressing or LMD. If LMD has been reported radiographically on baseline MRI, but is not suspected clinically by the Investigator, the patient must be free of neurological symptoms of LMD.
7.) Resting ECG with QTcF >470 msec on 2 or more timepoints within a 24-hour period, or history or family history of congenital long QT syndrome
8.) 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.
9.) 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.
16.) Phase 2a tumor profile exclusions: a) High-grade serious ovarian cancer b) ER+ breast cancer
10.) 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).
11.) 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.
12.) Pregnant or breastfeeding. Patients with elevated human chorionic gonadotropin due to underlying malignancy may be eligible if confirmed not to be pregnant.
14.) Patients currently treated with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants
15.) Any other prior or ongoing significant medical condition, physical finding, laboratory abnormality, psychiatric illness, or social situation that, in the opinion of the Investigator or Medical Monitor, could impact safety or compliance with study requirements or confounds the ability to interpret data.
2.) Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug. If previously irradiated, lesions must have demonstrated clear-cut progression prior to being eligible for evaluation as target lesions.
3.) Major surgery (excluding placement of vascular access) ≤28 days of the first dose of study drug.
4.) Symptomatic untreated or progressing brain metastases. Stable, treated brain metastases are allowed if no evidence of radiologic or clinical progression or corticosteroid use for at least 4 weeks.

The study team makes the final eligibility decision.

Where it's taking place

United States

Questions & answers

Do participants get paid in this trial?

This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.

Is it free to join, and do I need insurance?

Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.

How long does this study last?

The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.

Who can join this trial?

This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.

Where is this trial taking place?

Study sites include United States. Enter your location above to see the nearest site and check your eligibility.

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BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.