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NCT05128825PHASE2Recruiting

A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer

K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Start Date

2/17/2022

Completion Date

6/30/2027

Summary

This is a multi-part Phase 2 study to evaluate the efficacy and safety of azenosertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Part 2 of the study will be conducted in subjects whose tumors are Cyclin E1 positive as determined by central review using the Sponsor's investigational clinical trial assay.

Detailed Description

A Phase 2 study to evaluate the efficacy and safety of azenossertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Azenosertib is a selective and orally bioavailable inhibitor of WEE1. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage leading to mitotic catastrophe and cancer cell death. The study consists of two parts: Part 1: All comers, no biomarker status required (completed enrollment) Part 2: Cyclin E1 positive protein expression required

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Age ≥18 years 2. High-grade serous ovarian, fallopian tube or primary peritoneal cancer 3. Tumor testing (archival acceptable) confirms a positive Cyclin E1 protein status result determined by IHC using the Sponsor's investigational clinical trial assay 4. Prior therapy: 1. Subjects must have platinum-resistant disease 2. Parts 2a and 2b: One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab) 3. Part 2c: Subjects with PROC may have 1 to 4 prior lines or regimens. Prior treatment in this cohort includes a weekly taxane regimen, either as single agent or in combination, per protocol 4. Prior bevacizumab treatment is required, if eligible per standard of care 5. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care 6. Prior mirvetuximab treatment is required, if eligible per standard of care 5. Measurable disease per RECIST Version 1.1. 6. Adequate hematologic and organ function, as defined in protocol 7. ECOG 0-1 Exclusion Criteria: 1. Primary platinum-refractory disease 2. Subjects with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, low-grade, borderline, or other ovarian tumors 3. Any of the following treatment interventions within the specified time frame prior to C1D1: 1. Major surgery within 28 days 2. Hospitalization within 14 days 3. Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter); 4. Radiation therapy within 21 days; 5. Autologous or allogeneic stem cell transplant within 3 months. 6. Current use of any other investigational drug therapy \<28 days or 5 half-lives (whichever is shorter). 7. Inability to discontinue treatment prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements that are strong or moderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 days prior to C1D1. 4. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, PKMYT1 inhibitor, or CHK1/2 inhibitor. 5. A serious illness or medical condition(s) including, but not limited to: 1. Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible. 2. Myocardial impairment resulting in heart failure (NYHA Class II-IV) 3. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or may interfere with interpretation of study results 4. Acute kidney injury requiring intervention or intravenous fluid in the last 14 days or presence of indwelling urinary catheter or percutaneous nephrostomy. 5. Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for intravenous alimentation, active peptic ulcer, chronic diarrhea or vomiting considered to be clinically significant in the judgment of the Investigator, or prior surgical procedures affecting absorption. 6. Active, uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral) must have completed such treatment and the infection must be considered controlled/resolved (and afebrile) by the Investigator for at least 7 days before C1D1 7. Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT scan, recent hospitalization for small bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1. 6. Unresolved toxicity of Grade \>1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation). 7. Pregnant or lactating female subject or female subject of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1. 8. History of another malignancy in the previous 2 years, unless cured by surgery alone and continuously disease free. Exceptions include appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome. 9. Subjects who are known to be immunocompromised or HIV-positive on highly active anti-retroviral therapy. 10. Subjects with known active hepatitis B or hepatitis C infection. 11. Individuals who are judged by the Investigator to be unsuitable as study subjects. 12. Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.

Interventions

DRUG

azenosertib

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Conditions

High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Locations

Site 0170-USA Mitchell Cancer Institute

Mobile, Alabama 36604

United States

Site 0143 - HonorHealth

Phoenix, Arizona 85016

United States

Site 0102 - University of Arizona Cancer Center

Tucson, Arizona 85724

United States

Site 0258 - UC San Diego Moores Cancer Center

La Jolla, California 92037

United States

Site 0287 - Ridley Tree Cancer Center

Santa Barbara, California 93105

United States

Site 0135 - Rocky Mountain Cancer Centers

Lone Tree, Colorado 80218

United States

Site 0158 - Hartford HealthCare

Hartford, Connecticut 06106

United States

Site 0239 - Florida Cancer Specialists - East

Daytona Beach, Florida 32117

United States

Site 0241 - Florida Cancer Specialist - North

Lecanto, Florida 34461

United States

Site 0173 - Mount Sinai Medical Center

Miami Beach, Florida 33140

United States

Site 0308 - Advent Health

Orlando, Florida 32803

United States

Site 0108 - Emory University Hospital

Atlanta, Georgia 30322

United States

Site 0236 - Memorial Health

Savannah, Georgia 31404

United States

Site 0324 - Illinois Cancer Specialists

Niles, Illinois 60714

United States

Site 0284 - Community Cancer Center North

Indianapolis, Indiana 46250

United States

Site 0217 - St Vincent Hospital and Health Care Centers

Indianapolis, Indiana 46260

United States

Site 0251 - Norton Cancer Institute

Louisville, Kentucky 40202

United States

Site 0146 - Maryland Oncology Hematology, PA

Rockville, Maryland 20876

United States

Site 0221 - Tufts Medical Center - PPDS

Boston, Massachusetts 02111

United States

Site 0104 - Dana Farber Cancer Institute

Boston, Massachusetts 02215

United States

Site 0307 - Lahey Hospital and Medical Center

Burlington, Massachusetts 01805

United States

Site 0263 - Baystate Medical Center

Springfield, Massachusetts 01199

United States

Site 0101 - Barbara Ann Karmanos Cancer Institute

Detroit, Michigan 48201

United States

Site 0228 - Corewell Health Medical Group West

Grand Rapids, Michigan 49503

United States

Site 0288 - Minnesota Oncology Hematology - Maplewood

Maplewood, Minnesota 55109

United States

Site 0226 - CoxHealth

Springfield, Missouri 65807

United States

Site 0317 - Nebraska Methodist Hospital

Omaha, Nebraska 68114

United States

Site 0213 - Center of Hope

Reno, Nevada 89511

United States

Site 0231 - Northwell Health Cancer Institute

Manhasset, New York 11030

United States

Site 0126 - Wilmot Cancer Center

Rochester, New York 14642

United States

Site 0259 - Duke Cancer Center

Durham, North Carolina 27710

United States

Site 0147 - Trihealth Cancer Institute - Harold and Eugen

Cincinnati, Ohio 45242

United States

Site 0243 - Mark H Zangmeister Cancer Center

Columbus, Ohio 43219

United States

Site 0214-Ohio State University Comprehensive Cancer Center

Hilliard, Ohio 43026

United States

Site 0316 - Willamette Valley Cancer Institute/Oncology Associates of Oregon

Eugene, Oregon 97401

United States

Site 0232 - University of Pennsylvania

Philadelphia, Pennsylvania 19104

United States

Site 0178 - Thomas Jefferson University

Philadelphia, Pennsylvania 19107

United States

Site 0277 - Alliance Cancer Specialist, PC

Wynnewood, Pennsylvania 19096

United States

Site 0132 - Avera Cancer Institute

Sioux Falls, South Dakota 57105

United States

Site 0103 - University of Texas MD Anderson Cancer Center

Houston, Texas 77030

United States

Site 0234 - University of Texas Health, Memorial Hermann Hospital

Houston, Texas 77030

United States

Site 0203 - Texas Oncology

Tyler, Texas 75702

United States

Site 0295 - Virginia Oncology Associates

Chesapeake, Virginia 23320

United States

Site 0322 - Inova Schar Cancer Institute

Fairfax, Virginia 22031

United States

Site 0323 - Compass Oncology

Vancouver, Washington 98684

United States

Site 2715 - Icon Cancer Centre - Chermside

Chermside, Queensland 4032

Australia

Site 2707 - Mater Brisbane

South Brisbane, Queensland 4101

Australia

Site 2709 - Cancer Research SA

Adelaide, South Australia 5037

Australia

Site 2702 - Burnside War Memorial Hospital - The Brian Fricker Oncology Centre

Toorak Gardens, South Australia 5065

Australia

Site 2716 - Epworth Healthcare Freemasons

East Melbourne, Victoria 3002

Australia

Site 2701 - Sir Charles Gairdner Hospital

Nedlands, Western Australia 6009

Australia

Site 2717 - St John of God Hospital Subiaco

Subiaco, Western Australia 6008

Australia

Site 3102 - Cliniques Universitaires Saint-Luc

Brussels, Brussels Capital 1200

Belgium

Site 3101 - AZORG - Aalst

Aalst, Oost-Vlaanderen 9300

Belgium

Site 3105 - UZ Leuven

Leuven, Vlaams Brabant 3000

Belgium

Site 3616 - Centre Antoine Lacassagne

Nice, Alpes-Maritimes 06100

France

Site 3611 - ICANS - Institut de cancérologie Strasbourg Europe

Strasbourg, Bas-Rhin 67200

France

Site 3601 - Centre Georges François Leclerc

Dijon, Côte-d'Or 21079

France

Site 3613 - CHRU Besancon - Hopital Jean Minjoz

Besançon, Doubs 25030

France

Site 3617 - CHU de Brest - Hôpital La Cavale Blanche

Brest, Finistere 29200

France

Site 3603 - Institut Claudius Regaud

Toulouse, Haute-Garonne 31000

France

Site 3602 - Centre Oscar Lambret

Lille, Nord 59000

France

Site 3615 - Hôpital Cochin Port-Royal AP-HP

Paris, Paris 75181

France

Site 3614 - Institut de Cancerologie de l'oust

Saint-Herblain, Pays de la Loire Region 44800

France

Site 3608 - Hospices Civils de Lyon - Hôpital Lyon Sud

Pierre-Bénite, Rhône 69310

France

Site 3619 - Centre Léon Bérard

Lyon, 69373

France

Site 3620 - CHU de Strasbourg - Hopital de Hautepierre

Strasbourg, 67200

France

Site 3604 - Institut Gustave Roussy

Villejuif, 94800

France

Site 3302 - Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale

Naples, Campania 80131

Italy

Site 3308 - Azienda Ospedaliero Universitaria Di Modena Policlinico

Modena, Emilia-Romagna 41124

Italy

Site 3312 - Centro di Riferimento Oncologico

Aviano, Friuli Venezia Giulia 33081

Italy

Site 3304 - Fondazione Policlinico Universitario A Gemelli

Rome, Lazio 168

Italy

Site 3305 - Istituto Europeo di Oncologia

Milan, Lombardy 20141

Italy

Site 3307 - Ospedale San Raffaele S.r.l.

Milan, Milano 20132

Italy

Site 3311 - Azienda Ospedaliera Universitaria Integrata Di Verona

Verona, Veneto 37126

Italy

Site 3303 - Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti

Bologna, 40138

Italy

Site 2414 - Med-Polonia Sp. z o.o.

Poznan, Greater Poland Voivodeship 60-693

Poland

Site 2405 - Centrum Badan Klinicznych JCI

Krakow, Lesser Poland Voivodeship 30-348

Poland

Site 2404 - Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie

Warsaw, Masovian Voivodeship 02-781

Poland

Site 2419 - Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku

Bialystok, Podlaskie Voivodeship 15-027

Poland

Site 2421 - Szpitale Pomorskie Sp. z o. o.

Gdynia, Pomeranian Voivodeship 81-519

Poland

Site 2908 - National Cancer Center

Goyang-si, Gyeonggi-do 10408

South Korea

Site 2905 - Seoul National University Hospital

Seoul, 03080

South Korea

Site 2909 - Severance Hospital Yonsei University Health System

Seoul, 03722

South Korea

Site 2904 - Asan Medical Center

Seoul, 05505

South Korea

Site 2906 - Gangnam Severance Hospital, Yonsei University Health System

Seoul, 06273

South Korea

Site 2907 - Samsung Medical Center

Seoul, 06351

South Korea

Site 3511 - Instituto de Investigacion Oncologica Vall d'Hebron

Barcelona, Barcelona 8035

Spain

Site 3517 - Clinica Universidad de Navarra

Madrid, Madrid 28027

Spain

Site 3516 - Hospital Universitario Virgen de La Arrixaca

Murcia, Murcia 30120

Spain

Site 3501 - Hospital Clinico Universitario de Valencia

Valencia, Valencia 46010

Spain

Site 3502 - Hospital Universitario La Paz

Madrid, 28046

Spain