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

Launched by 858 THERAPEUTICS, INC. · Apr 30, 2024

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ClinConnect Summary

This clinical trial is studying a new medication called ETX-19477, which targets a specific enzyme involved in cancer growth. Researchers want to find out how safe the drug is, how the body processes it, and whether it can help treat patients with advanced solid tumors, including different types of breast, ovarian, prostate, and colorectal cancers. The trial is currently looking for participants aged 18 and older who have been diagnosed with advanced cancer that has not responded to standard treatments.

Eligible participants should have a confirmed diagnosis of advanced solid tumors and must have experienced progression or intolerance to their most recent treatment. Those with certain genetic mutations, such as BRCA2, may be prioritized for enrollment. Throughout the trial, participants will receive the study drug and be monitored for any side effects and how well the treatment is working. It’s important to note that individuals with certain health conditions, like significant heart disease or active infections, may not be able to participate. If you or a loved one are considering joining this study, you can expect close medical supervision and a chance to contribute to important cancer research.

Gender

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Eligibility criteria

• Inclusion Criteria:
• • 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.
• • 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 prior to enrollment.
• • 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.
• • 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.
• • 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