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

NCT05128825 · K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
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Official title
A Phase 2 Open-Label, Multicenter Study To Evaluate Efficacy And Safety Of ZN-c3 In Subjects With High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer (DENALI / ZN-c3-005 / GOG-3066)
About this study
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
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.
Study design
Enrollment target: 310 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2022-02-17
Estimated completion: 2027-06-30
Last updated: 2026-04-15
Interventions
Drug: azenosertib
Primary outcomes
  • Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2] (Up to approximately 12 months from the enrollment of the last subject)
Sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc · industry
Contacts & investigators
ContactProject Director · contact · medicalaffairs@zentalis.com · 858.263.4333
All locations (90)
Site 0170-USA Mitchell Cancer InstituteRecruiting
Mobile, Alabama, United States
Site 0143 - HonorHealthRecruiting
Phoenix, Arizona, United States
Site 0102 - University of Arizona Cancer CenterRecruiting
Tucson, Arizona, United States
Site 0258 - UC San Diego Moores Cancer CenterActive Not Recruiting
La Jolla, California, United States
Site 0287 - Ridley Tree Cancer CenterActive Not Recruiting
Santa Barbara, California, United States
Site 0135 - Rocky Mountain Cancer CentersActive Not Recruiting
Lone Tree, Colorado, United States
Site 0158 - Hartford HealthCareRecruiting
Hartford, Connecticut, United States
Site 0239 - Florida Cancer Specialists - EastRecruiting
Daytona Beach, Florida, United States
Site 0173 - Mount Sinai Medical CenterRecruiting
Miami Beach, Florida, United States
Site 0308 - Advent HealthRecruiting
Orlando, Florida, United States
Site 0108 - Emory University HospitalRecruiting
Atlanta, Georgia, United States
Site 0236 - Memorial HealthActive Not Recruiting
Savannah, Georgia, United States
Site 0324 - Illinois Cancer SpecialistsActive Not Recruiting
Niles, Illinois, United States
Site 0284 - Community Cancer Center NorthRecruiting
Indianapolis, Indiana, United States
Site 0217 - St Vincent Hospital and Health Care CentersRecruiting
Indianapolis, Indiana, United States
Site 0251 - Norton Cancer InstituteRecruiting
Louisville, Kentucky, United States
Site 0146 - Maryland Oncology Hematology, PAActive Not Recruiting
Rockville, Maryland, United States
Site 0221 - Tufts Medical Center - PPDSRecruiting
Boston, Massachusetts, United States
Site 0104 - Dana Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Site 0307 - Lahey Hospital and Medical CenterRecruiting
Burlington, Massachusetts, United States
Site 0263 - Baystate Medical CenterRecruiting
Springfield, Massachusetts, United States
Site 0101 - Barbara Ann Karmanos Cancer InstituteRecruiting
Detroit, Michigan, United States
Site 0228 - Corewell Health Medical Group WestRecruiting
Grand Rapids, Michigan, United States
Site 0288 - Minnesota Oncology Hematology - MaplewoodRecruiting
Maplewood, Minnesota, United States
Site 0226 - CoxHealthActive Not Recruiting
Springfield, Missouri, United States
Site 0317 - Nebraska Methodist HospitalActive Not Recruiting
Omaha, Nebraska, United States
Site 0213 - Center of HopeRecruiting
Reno, Nevada, United States
Site 0231 - Northwell Health Cancer InstituteActive Not Recruiting
Manhasset, New York, United States
Site 0126 - Wilmot Cancer CenterRecruiting
Rochester, New York, United States
Site 0259 - Duke Cancer CenterRecruiting
Durham, North Carolina, United States
Site 0147 - Trihealth Cancer Institute - Harold and EugenRecruiting
Cincinnati, Ohio, United States
Site 0243 - Mark H Zangmeister Cancer CenterRecruiting
Columbus, Ohio, United States
Site 0214-Ohio State University Comprehensive Cancer CenterRecruiting
Hilliard, Ohio, United States
Site 0316 - Willamette Valley Cancer Institute/Oncology Associates of OregonRecruiting
Eugene, Oregon, United States
Site 0232 - University of PennsylvaniaRecruiting
Philadelphia, Pennsylvania, United States
Site 0178 - Thomas Jefferson UniversityRecruiting
Philadelphia, Pennsylvania, United States
Site 0277 - Alliance Cancer Specialist, PCActive Not Recruiting
Wynnewood, Pennsylvania, United States
Site 0132 - Avera Cancer InstituteRecruiting
Sioux Falls, South Dakota, United States
Site 0103 - University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
Site 0234 - University of Texas Health, Memorial Hermann HospitalRecruiting
Houston, Texas, United States
Site 0203 - Texas OncologyRecruiting
Tyler, Texas, United States
Site 0295 - Virginia Oncology AssociatesRecruiting
Chesapeake, Virginia, United States
Site 0322 - Inova Schar Cancer InstituteRecruiting
Fairfax, Virginia, United States
Site 0323 - Compass OncologyActive Not Recruiting
Vancouver, Washington, United States
Site 2715 - Icon Cancer Centre - ChermsideRecruiting
Chermside, Queensland, Australia
Site 2707 - Mater BrisbaneRecruiting
South Brisbane, Queensland, Australia
Site 2709 - Cancer Research SARecruiting
Adelaide, South Australia, Australia
Site 2702 - Burnside War Memorial Hospital - The Brian Fricker Oncology CentreRecruiting
Toorak Gardens, South Australia, Australia
Site 2716 - Epworth Healthcare FreemasonsRecruiting
East Melbourne, Victoria, Australia
Site 2701 - Sir Charles Gairdner HospitalRecruiting
Nedlands, Western Australia, Australia
Site 2717 - St John of God Hospital SubiacoRecruiting
Subiaco, Western Australia, Australia
Site 3102 - Cliniques Universitaires Saint-LucRecruiting
Brussels, Brussels Capital, Belgium
Site 3101 - AZORG - AalstActive Not Recruiting
Aalst, Oost-Vlaanderen, Belgium
Site 3105 - UZ LeuvenRecruiting
Leuven, Vlaams Brabant, Belgium
Site 3616 - Centre Antoine LacassagneRecruiting
Nice, Alpes-Maritimes, France
Site 3611 - ICANS - Institut de cancérologie Strasbourg EuropeRecruiting
Strasbourg, Bas-Rhin, France
Site 3601 - Centre Georges François LeclercRecruiting
Dijon, Côte-d'Or, France
Site 3613 - CHRU Besancon - Hopital Jean MinjozRecruiting
Besançon, Doubs, France
Site 3617 - CHU de Brest - Hôpital La Cavale BlancheRecruiting
Brest, Finistere, France
Site 3603 - Institut Claudius RegaudRecruiting
Toulouse, Haute-Garonne, France
Site 3602 - Centre Oscar LambretRecruiting
Lille, Nord, France
Site 3615 - Hôpital Cochin Port-Royal AP-HPRecruiting
Paris, Paris, France
Site 3614 - Institut de Cancerologie de l'oustRecruiting
Saint-Herblain, Pays de la Loire Region, France
Site 3608 - Hospices Civils de Lyon - Hôpital Lyon SudRecruiting
Pierre-Bénite, Rhône, France
Site 3619 - Centre Léon BérardRecruiting
Lyon, France
Site 3620 - CHU de Strasbourg - Hopital de HautepierreRecruiting
Strasbourg, France
Site 3604 - Institut Gustave RoussyRecruiting
Villejuif, France
Site 3302 - Istituto Nazionale Tumori IRCCS Fondazione Giovanni PascaleRecruiting
Naples, Campania, Italy
Site 3308 - Azienda Ospedaliero Universitaria Di Modena PoliclinicoRecruiting
Modena, Emilia-Romagna, Italy
Site 3312 - Centro di Riferimento OncologicoRecruiting
Aviano, Friuli Venezia Giulia, Italy
Site 3304 - Fondazione Policlinico Universitario A GemelliRecruiting
Rome, Lazio, Italy
Site 3305 - Istituto Europeo di OncologiaRecruiting
Milan, Lombardy, Italy
Site 3307 - Ospedale San Raffaele S.r.l.Recruiting
Milan, Milano, Italy
Site 3311 - Azienda Ospedaliera Universitaria Integrata Di VeronaRecruiting
Verona, Veneto, Italy
Site 3303 - Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via MassarentiRecruiting
Bologna, Italy
Site 2414 - Med-Polonia Sp. z o.o.Active Not Recruiting
Poznan, Greater Poland Voivodeship, Poland
Site 2405 - Centrum Badan Klinicznych JCIRecruiting
Krakow, Lesser Poland Voivodeship, Poland
Site 2404 - Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w WarszawieRecruiting
Warsaw, Masovian Voivodeship, Poland
Site 2419 - Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w BialymstokuRecruiting
Bialystok, Podlaskie Voivodeship, Poland
Site 2421 - Szpitale Pomorskie Sp. z o. o.Recruiting
Gdynia, Pomeranian Voivodeship, Poland
Site 2905 - Seoul National University HospitalRecruiting
Seoul, South Korea
Site 2909 - Severance Hospital Yonsei University Health SystemRecruiting
Seoul, South Korea
Site 2904 - Asan Medical CenterRecruiting
Seoul, South Korea
Site 2906 - Gangnam Severance Hospital, Yonsei University Health SystemRecruiting
Seoul, South Korea
Site 2907 - Samsung Medical CenterRecruiting
Seoul, South Korea
Site 3511 - Instituto de Investigacion Oncologica Vall d'HebronRecruiting
Barcelona, Barcelona, Spain
Site 3517 - Clinica Universidad de NavarraRecruiting
Madrid, Madrid, Spain
Site 3516 - Hospital Universitario Virgen de La ArrixacaRecruiting
Murcia, Murcia, Spain
Site 3501 - Hospital Clinico Universitario de ValenciaRecruiting
Valencia, Valencia, Spain
Site 3502 - Hospital Universitario La PazRecruiting
Madrid, Spain
A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer · TrialPath