[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06395519":3,"trial-entities:NCT06395519":269,"trial-summary:NCT06395519":279},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":6,"overall_status":7,"completion_date":8,"status_verified_date":9,"last_update_date":10,"start_date":11,"sponsor_name":12,"lead_sponsor_class":13,"has_dmc":14,"brief_summary":15,"detailed_description":16,"conditions":17,"keywords":31,"study_type":33,"primary_purpose":34,"phases":35,"enrollment_info":38,"interventions":41,"primary_outcomes":49,"secondary_outcomes":54,"sex":78,"minimum_age":79,"maximum_age":80,"healthy_volunteers":14,"eligibility_criteria":81,"std_ages":105,"locations":108,"central_contacts":258,"overall_officials":263,"references":267,"see_also_links":268},"NCT06395519","ETX-19477-101","A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies","RECRUITING","2026-12","2026-03","2026-03-27","2024-05-13","858 Therapeutics, Inc.","INDUSTRY",false,"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.","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.\n\nPoly (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\u002For 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.",[18,19,20,21,22,23,24,25,26,27,28,29,30],"Advanced or Metastatic Solid Tumors","Breast Cancer","Ovarian Cancer","Prostate Cancer","Epithelial Ovarian Cancer","BRCA2 Mutation","ER+ Breast Cancer","Castrate Resistant Prostate Cancer","BRCA1 Mutation","BRCA Mutation","Endometrial Cancer","Colorectal Cancer","Gastric Cancer",[32],"PARG Inhibitor","INTERVENTIONAL","TREATMENT",[36,37],"PHASE1","PHASE2",{"count":39,"type":40},120,"ESTIMATED",[42],{"type":43,"name":44,"description":45,"armGroupLabels":46},"DRUG","ETX-19477","Oral medication taken daily",[47,48],"Phase 1 Part 1: Monotherapy Dose Escalation","Phase 1 Part 2: Monotherapy Dose Expansion",[50],{"measure":51,"description":52,"timeFrame":53},"To characterize the safety and tolerability of ETX-19477, the maximum tolerated dose (MTD) and\u002For RP2D of ETX-19477","Frequency of dose-limiting toxicities (DLTs), frequency and severity of AEs, including abnormal ECG parameters, and serious adverse events (SAEs)","6 months",[55,59,62,65,68,72,75],{"measure":56,"description":57,"timeFrame":58},"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).","3 months",{"measure":60,"description":61,"timeFrame":58},"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.",{"measure":63,"description":64,"timeFrame":58},"To characterize the pharmacokinetic (PK) profile of ETX-19477 by measuring elimination half-life (t1\u002F2)","Elimination half-life (t1\u002F2) for single dose and at steady state with trough levels at the beginning of the next cycle.",{"measure":66,"description":67,"timeFrame":58},"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",{"measure":69,"description":70,"timeFrame":71},"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","2 years",{"measure":73,"description":74,"timeFrame":71},"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",{"measure":76,"description":77,"timeFrame":71},"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","ALL","18 Years",null,{"inclusion":82,"exclusion":91,"raw_text":104},[83,84,85,86,87,88,89,90],"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\u002Fmetastatic 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.",[92,93,94,95,96,97,98,99,100,101,102,103],"Receiving continuous corticosteroids at prednisone-equivalent dose of \\>10 mg\u002Fday. Chronic systemic corticosteroid therapy for physiologic replacement (≤10 mg\u002Fday 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\u002For 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\u002FQTc 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\u002Fcurrent 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","Inclusion Criteria:\n\n* Males and females of age ≥ 18 years at the time of signing the informed consent document.\n* Histologically or cytologically confirmed advanced (incurable recurrent, unresectable, or metastatic) solid cancer, excluding primary central nervous system (CNS) tumors.\n* 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.\n* Measurable disease per RECIST v1.1.\n* ECOG performance status 0-1.\n* Progression on or after or intolerance to most recent systemic therapy. Prior treatment in the recurrent\u002Fmetastatic 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.\n* No investigational agent within 3 weeks or 5 half-lives (whichever is shorter; minimum of 2 weeks) prior to first dose of study drug.\n* Life expectancy of at least 3 months.\n\nExclusion Criteria:\n\n* Receiving continuous corticosteroids at prednisone-equivalent dose of \\>10 mg\u002Fday. Chronic systemic corticosteroid therapy for physiologic replacement (≤10 mg\u002Fday of prednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled, topical, intra-nasal, intra-articular, or ophthalmic) are permitted.\n* Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks prior to the first dose of study drug.\n* 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.\n* 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\u002For peritoneal fluid drainage within 8 weeks prior to the first dose of study drug.\n* 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.\n* 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\u002FQTc interval, or history of additional risk factors for torsades de pointes (Tdp).\n* 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.\n* 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.\n* 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).\n* Known other previous\u002Fcurrent 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.\n* 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.\n* Patients currently treated with therapeutic doses of warfarin sodium (Coumadin®) or any other coumarin-derivative anticoagulants",[106,107],"ADULT","OLDER_ADULT",[109,122,133,143,154,165,175,185,192,203,214,225,236,247],{"facility":110,"status":7,"city":111,"state":112,"zip":113,"country":114,"contacts":115,"geoPoint":119},"Mayo Clinic","Phoenix","Arizona","85054","United States",[116],{"name":117,"role":118},"Felipe Batalini, MD","PRINCIPAL_INVESTIGATOR",{"lat":120,"lon":121},33.44838,-112.07404,{"facility":123,"status":7,"city":124,"state":125,"zip":126,"country":114,"contacts":127,"geoPoint":130},"Yale University, Yale Cancer Center","New Haven","Connecticut","06510",[128],{"name":129,"role":118},"Michael Cecchini, MD",{"lat":131,"lon":132},41.30815,-72.92816,{"facility":110,"status":7,"city":134,"state":135,"zip":136,"country":114,"contacts":137,"geoPoint":140},"Jacksonville","Florida","32224",[138],{"name":139,"role":118},"Pooja Advani, MD",{"lat":141,"lon":142},30.33218,-81.65565,{"facility":144,"status":7,"city":145,"state":146,"zip":147,"country":114,"contacts":148,"geoPoint":151},"University of Chicago Medical Center","Chicago","Illinois","60637",[149],{"name":150,"role":118},"Han Cun, MD",{"lat":152,"lon":153},41.85003,-87.65005,{"facility":155,"status":7,"city":156,"state":157,"zip":158,"country":114,"contacts":159,"geoPoint":162},"Massachusetts General Hospital","Boston","Massachusetts","02114",[160],{"name":161,"role":118},"Richard T Penson, MD",{"lat":163,"lon":164},42.35843,-71.05977,{"facility":110,"status":7,"city":166,"state":167,"zip":168,"country":114,"contacts":169,"geoPoint":172},"Rochester","Minnesota","55905",[170],{"name":171,"role":118},"Siddhartha Yadav, MD",{"lat":173,"lon":174},44.02163,-92.4699,{"facility":176,"status":7,"city":177,"state":177,"zip":178,"country":114,"contacts":179,"geoPoint":182},"Laura & Isaac Perlmutter Cancer Center at NYU Langone Health","New York","10016",[180],{"name":181,"role":118},"Nancy Chan, MD",{"lat":183,"lon":184},40.71427,-74.00597,{"facility":186,"status":7,"city":177,"state":177,"zip":187,"country":114,"contacts":188,"geoPoint":191},"Memorial Sloan Kettering Cancer Center","10065",[189],{"name":190,"role":118},"Ezra Y Rosen, MD, PhD",{"lat":183,"lon":184},{"facility":193,"status":7,"city":194,"state":195,"zip":196,"country":114,"contacts":197,"geoPoint":200},"Stefanie Spielman Comprehensive Breast Center","Columbus","Ohio","43212",[198],{"name":199,"role":118},"Sagar Sardesai, MBBS",{"lat":201,"lon":202},39.96118,-82.99879,{"facility":204,"status":7,"city":205,"state":206,"zip":207,"country":114,"contacts":208,"geoPoint":211},"Thomas Jefferson University, Sidney Kimmel Comprehensive Cancer Center","Philadelphia","Pennsylvania","19107",[209],{"name":210,"role":118},"Kevin Zarrabi, MD",{"lat":212,"lon":213},39.95238,-75.16362,{"facility":215,"status":7,"city":216,"state":217,"zip":218,"country":114,"contacts":219,"geoPoint":222},"MD Anderson Cancer Center","Houston","Texas","77030",[220],{"name":221,"role":118},"Timothy A Yap, MD, PhD",{"lat":223,"lon":224},29.76328,-95.36327,{"facility":226,"status":7,"city":227,"state":228,"zip":229,"country":114,"contacts":230,"geoPoint":233},"START Center for Cancer Care - Mountain Region","Salt Lake City","Utah","84112",[231],{"name":232,"role":118},"William B. McKean, Jr, MD",{"lat":234,"lon":235},40.76078,-111.89105,{"facility":237,"status":7,"city":238,"state":239,"zip":240,"country":114,"contacts":241,"geoPoint":244},"Virginia Cancer Specialists","Fairfax","Virginia","22031",[242],{"name":243,"role":118},"Alexander I Spira, MD",{"lat":245,"lon":246},38.84622,-77.30637,{"facility":248,"status":7,"city":249,"state":250,"zip":251,"country":114,"contacts":252,"geoPoint":255},"Fred Hutchinson Cancer Center","Seattle","Washington","98109",[253],{"name":254,"role":118},"Kalyan Banda, MD",{"lat":256,"lon":257},47.60621,-122.33207,[259],{"name":12,"role":260,"phone":261,"email":262},"CONTACT","(858) 987-8380","dmccormick@8five8tx.com",[264],{"name":265,"affiliation":12,"role":266},"Daniel McCormick","STUDY_DIRECTOR",[],[],{"nct_id":4,"conditions":270,"biomarkers":278},[271,272,273,274,275,276,277],"Breast Carcinoma","Colorectal Carcinoma","Endometrial Carcinoma","Gastric Carcinoma","Malignant Ovarian Neoplasm","Prostate Carcinoma","Solid Neoplasm",[],{"nct_id":4,"found":280,"summary":281,"prompt_version":291},true,{"design":282,"status":283,"heading":284,"summary":285,"follow_up":286,"word_count":287,"commitments":288,"compensation":289,"drugs_mentioned":290},"This is an open-label study, meaning you and your doctors will know you are receiving ETX-19477. It will involve about 120 participants and has two parts: one to find the right dose and another to expand on those findings.","completed","A Study of ETX-19477 for Advanced Solid Tumors","This study is testing a new oral medication called ETX-19477 for people with advanced solid cancers, including breast, ovarian, and prostate cancer. The medication works by targeting a protein called PARG, which plays a role in how cancer cells repair their DNA. Researchers want to see how safe ETX-19477 is and what dose works best. They will also look at how your body handles the drug and if it helps shrink tumors. You may be able to join if you are at least 18 years old and have an advanced solid cancer that has spread or come back. The study is currently unclear on its recruitment status.","The primary endpoints for safety and tolerability, and the maximum tolerated dose, are measured at 6 months.",107,"You would take the oral medication ETX-19477 daily. The study will assess safety and tolerability, and determine the maximum tolerated dose or recommended dose within 6 months.","Not stated in the trial record.",[44],"v2"]