CClinicalTrials.gg
RecruitingNCT05128825DENALIUpdated Sep 29, 2026

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

A Phase 2 interventional study of azenosertib in High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer, sponsored by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. Recruiting at 86 sites in 8 countries. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-29.

Sponsored by K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
310
Allocation
Randomized
Ages
18 Years and older
Sex
Female
01

Study 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.

Read the detailed description

A 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. 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

02

Conditions studied

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

Browse trials for

Keywords

  • Cyclin E1, CCNE1, Ovarian Cancer, Platinum Resistant, WEE1 inhibitor, DENALI, GOG-3066
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
Female
Accepts healthy volunteers
No

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. 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
    3. Prior bevacizumab treatment is required, if eligible per standard of care
    4. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
    5. 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

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.
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
310 participants (estimated)

Study arms

  • Experimental
    Part 1a/1b (Completed Enrollment)

    Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule.

    Drug: azenosertib

  • Experimental
    Part 2a: Arm 1 (Completed Enrollment)

    Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule

    Drug: azenosertib

  • Experimental
    Part 2a: Arm 2 (Completed Enrollment)

    Azenosertib 300mg administered once daily on a 5 days on, 2 days off intermittent schedule

    Drug: azenosertib

  • Experimental
    Part 2b (Completed Enrollment)

    Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule

    Drug: azenosertib

  • Experimental
    Part 2c (Enrolling)

    Azenosertib 400mg administered once daily on a 5 days on, 2 days off intermittent schedule

    Drug: azenosertib

Interventions

  • Drugazenosertib

    Azenosertib (ZN-c3) will be administered orally.

    Also known as: ZN-c3

05

What researchers measure

Primary outcomes

  1. Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2]

    Participants who achieve partial response (PR) or complete response (CR) per RECIST v1.1 criteria.

    Time frame: Up to approximately 12 months from the enrollment of the last subject

Secondary outcomes

  1. Duration of response (DOR) defined by RECIST v1.1 [Part 2]

    Time from the date of first documented response (CR or PR that is subsequently confirmed per RECIST v1.1) until the date of progressive disease (PD) or death.

    Time frame: Up to approximately 12 months from the enrollment of the last subject

  2. Progression free survival (PFS) defined by RECIST v1.1 [Part 2]

    Time from the date of first dose until the date of PD or death.

    Time frame: Up to approximately 12 months from the enrollment of the last subject

  3. Clinical Benefit Rate (CBR) defined by RECIST v1.1 [Part 2]

    The percentage of participants who have at least 1 confirmed response of CR or PR, or stable disease for at least 16 weeks before any evidence of progression.

    Time frame: Up to approximately 12 months from the enrollment of the last subject

  4. CA-125 response by GCIG criteria [Part 2]

    The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline.

    Time frame: Up to approximately 12 months from the enrollment of the last subject

  5. Number of Subjects experiencing treatment emergent adverse events (TEAEs) [Part 2]

    Time frame: Up to approximately 12 months from the enrollment of the last subject

06

Study locations

77 of 86 sites recruiting
  • Site 0170-USA Mitchell Cancer Institute
    Mobile, Alabama 36604, United States
    Recruiting
  • Site 0143 - HonorHealth
    Phoenix, Arizona 85016, United States
    Recruiting
  • Site 0102 - University of Arizona Cancer Center
    Tucson, Arizona 85724, United States
    Recruiting
  • Site 0258 - UC San Diego Moores Cancer Center
    La Jolla, California 92037, United States
    Active, not recruiting
  • Site 0287 - Ridley Tree Cancer Center
    Santa Barbara, California 93105, United States
    Active, not recruiting
  • Site 0135 - Rocky Mountain Cancer Centers
    Lone Tree, Colorado 80218, United States
    Recruiting
  • Site 0158 - Hartford HealthCare
    Hartford, Connecticut 06106, United States
    Recruiting
  • Site 0241 - Florida Cancer Specialist - North
    Altamonte Springs, Florida 32701, United States
    Recruiting
  • Site 0173 - Mount Sinai Medical Center
    Miami Beach, Florida 33140, United States
    Recruiting
  • Site 0308 - Advent Health
    Orlando, Florida 32803, United States
    Recruiting
  • Site 0239 - Florida Cancer Specialists - East
    Wellington, Florida 33414, United States
    Recruiting
  • Site 0108 - Emory University Hospital
    Atlanta, Georgia 30322, United States
    Recruiting
  • Site 0236 - Memorial Health
    Savannah, Georgia 31404, United States
    Active, not recruiting
  • Site 0324 - Illinois Cancer Specialists
    Niles, Illinois 60714, United States
    Active, not recruiting
  • Site 0284 - Community Cancer Center North
    Indianapolis, Indiana 46250, United States
    Recruiting
  • Site 0217 - St Vincent Hospital and Health Care Centers
    Indianapolis, Indiana 46260, United States
    Recruiting
  • Site 0251 - Norton Cancer Institute
    Louisville, Kentucky 40202, United States
    Recruiting
  • Site 0146 - Maryland Oncology Hematology, PA
    Rockville, Maryland 20876, United States
    Active, not recruiting
  • Site 0221 - Tufts Medical Center - PPDS
    Boston, Massachusetts 02111, United States
    Recruiting
  • Site 0104 - Dana Farber Cancer Institute
    Boston, Massachusetts 02215, United States
    Recruiting
  • Site 0307 - Lahey Hospital and Medical Center
    Burlington, Massachusetts 01805, United States
    Recruiting
  • Site 0263 - Baystate Medical Center
    Springfield, Massachusetts 01199, United States
    Recruiting
  • Site 0101 - Barbara Ann Karmanos Cancer Institute
    Detroit, Michigan 48201, United States
    • Robert Morris · Principal investigator
    Recruiting
  • Site 0228 - Corewell Health Medical Group West
    Grand Rapids, Michigan 49503, United States
    Recruiting
  • Site 0288 - Minnesota Oncology Hematology - Maplewood
    Maplewood, Minnesota 55109, United States
    Recruiting
  • Site 0226 - CoxHealth
    Springfield, Missouri 65807, United States
    Active, not recruiting
  • Site 0317 - Nebraska Methodist Hospital
    Omaha, Nebraska 68114, United States
    Active, not recruiting
  • Site 0213 - Center of Hope
    Reno, Nevada 89511, United States
    Recruiting
  • Site 0231 - Northwell Health Cancer Institute
    Manhasset, New York 11030, United States
    Active, not recruiting
  • Site 0126 - Wilmot Cancer Center
    Rochester, New York 14642, United States
    Recruiting
  • Site 0259 - Duke Cancer Center
    Durham, North Carolina 27710, United States
    Recruiting
  • Site 0147 - Trihealth Cancer Institute - Harold and Eugen
    Cincinnati, Ohio 45242, United States
    Recruiting
  • Site 0243 - Mark H Zangmeister Cancer Center
    Columbus, Ohio 43219, United States
    Recruiting
  • Site 0214-Ohio State University Comprehensive Cancer Center
    Hilliard, Ohio 43026, United States
    Recruiting
  • Site 0316 - Willamette Valley Cancer Institute/Oncology Associates of Oregon
    Eugene, Oregon 97401, United States
    Recruiting
  • Site 0232 - University of Pennsylvania
    Philadelphia, Pennsylvania 19104, United States
    Recruiting
  • Site 0178 - Thomas Jefferson University
    Philadelphia, Pennsylvania 19107, United States
    Recruiting
  • Site 0277 - Alliance Cancer Specialist, PC
    Wynnewood, Pennsylvania 19096, United States
    Active, not recruiting
  • Site 0132 - Avera Cancer Institute
    Sioux Falls, South Dakota 57105, United States
    Recruiting
  • Site 0103 - University of Texas MD Anderson Cancer Center
    Houston, Texas 77030, United States
    Recruiting
  • Site 0203 - Texas Oncology
    Tyler, Texas 75702, United States
    Recruiting
  • Site 0295 - Virginia Oncology Associates
    Chesapeake, Virginia 23320, United States
    Recruiting
  • Site 0322 - Inova Schar Cancer Institute
    Fairfax, Virginia 22031, United States
    Recruiting
  • Site 2715 - Icon Cancer Centre - Chermside
    Chermside, Queensland 4032, Australia
    Recruiting
  • Site 2707 - Mater Brisbane
    South Brisbane, Queensland 4101, Australia
    Recruiting
  • Site 2709 - Cancer Research SA
    Adelaide, South Australia 5037, Australia
    Recruiting
  • Site 2702 - Burnside War Memorial Hospital - The Brian Fricker Oncology Centre
    Toorak Gardens, South Australia 5065, Australia
    Recruiting
  • Site 2716 - Epworth Healthcare Freemasons
    East Melbourne, Victoria 3002, Australia
    Recruiting
  • Site 2701 - Sir Charles Gairdner Hospital
    Nedlands, Western Australia 6009, Australia
    Recruiting
  • Site 2717 - St John of God Hospital Subiaco
    Subiaco, Western Australia 6008, Australia
    Recruiting
  • Site 3102 - Cliniques Universitaires Saint-Luc
    Brussels, Brussels Capital 1200, Belgium
    Recruiting
  • Site 3105 - UZ Leuven
    Leuven, Vlaams Brabant 3000, Belgium
    Recruiting
  • Site 3616 - Centre Antoine Lacassagne
    Nice, Alpes-Maritimes 06100, France
    Recruiting
  • Site 3601 - Centre Georges François Leclerc
    Dijon, Côte-d'Or 21079, France
    Recruiting
  • Site 3613 - CHRU Besancon - Hopital Jean Minjoz
    Besançon, Doubs 25030, France
    Recruiting
  • Site 3617 - CHU de Brest - Hôpital La Cavale Blanche
    Brest, Finistere 29200, France
    Recruiting
  • Site 3603 - Institut Claudius Regaud
    Toulouse, Haute-Garonne 31000, France
    Recruiting
  • Site 3602 - Centre Oscar Lambret
    Lille, Nord 59000, France
    Recruiting
  • Site 3615 - Hôpital Cochin Port-Royal AP-HP
    Paris, Paris 75181, France
    Recruiting
  • Site 3614 - Institut de Cancerologie de l'oust
    Saint-Herblain, Pays de la Loire Region 44800, France
    Recruiting
  • Site 3608 - Hospices Civils de Lyon - Hôpital Lyon Sud
    Pierre-Bénite, Rhône 69310, France
    Recruiting
  • Site 3619 - Centre Léon Bérard
    Lyon, 69373, France
    Recruiting
  • Site 3620 - CHU de Strasbourg - Hopital de Hautepierre
    Strasbourg, 67200, France
    Recruiting
  • Site 3604 - Institut Gustave Roussy
    Villejuif, 94800, France
    Recruiting
  • Site 3302 - Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale
    Naples, Campania 80131, Italy
    Recruiting
  • Site 3308 - Azienda Ospedaliero Universitaria Di Modena Policlinico
    Modena, Emilia-Romagna 41124, Italy
    Recruiting
  • Site 3312 - Centro di Riferimento Oncologico
    Aviano, Friuli Venezia Giulia 33081, Italy
    Recruiting
  • Site 3304 - Fondazione Policlinico Universitario A Gemelli
    Rome, Lazio 168, Italy
    Recruiting
  • Site 3305 - Istituto Europeo di Oncologia
    Milan, Lombardy 20141, Italy
    Recruiting
  • Site 3307 - Ospedale San Raffaele S.r.l.
    Milan, Milano 20132, Italy
    Recruiting
  • Site 3311 - Azienda Ospedaliera Universitaria Integrata Di Verona
    Verona, Veneto 37126, Italy
    Recruiting
  • Site 3303 - Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-Via Massarenti
    Bologna, 40138, Italy
    Recruiting
  • Site 2405 - Centrum Badan Klinicznych JCI
    Krakow, Lesser Poland Voivodeship 30-348, Poland
    Recruiting
  • Site 2419 - Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku
    Bialystok, Podlaskie Voivodeship 15-027, Poland
    Recruiting
  • Site 2421 - Szpitale Pomorskie Sp. z o. o.
    Gdynia, Pomeranian Voivodeship 81-519, Poland
    Recruiting
  • Site 2908 - National Cancer Center
    Goyang-si, Gyeonggi-do 10408, South Korea
    Recruiting
  • Site 2905 - Seoul National University Hospital
    Seoul, 03080, South Korea
    Recruiting
  • Site 2909 - Severance Hospital Yonsei University Health System
    Seoul, 03722, South Korea
    Recruiting
  • Site 2904 - Asan Medical Center
    Seoul, 05505, South Korea
    Recruiting
  • Site 2906 - Gangnam Severance Hospital, Yonsei University Health System
    Seoul, 06273, South Korea
    Recruiting
  • Site 2907 - Samsung Medical Center
    Seoul, 06351, South Korea
    Recruiting
  • Site 3511 - Instituto de Investigacion Oncologica Vall d'Hebron
    Barcelona, Barcelona 8035, Spain
    Recruiting
  • Site 3517 - Clinica Universidad de Navarra
    Madrid, Madrid 28027, Spain
    Recruiting
  • Site 3516 - Hospital Universitario Virgen de La Arrixaca
    Murcia, Murcia 30120, Spain
    Recruiting
  • Site 3501 - Hospital Clinico Universitario de Valencia
    Valencia, Valencia 46010, Spain
    Recruiting
  • Site 3502 - Hospital Universitario La Paz
    Madrid, 28046, Spain
    Recruiting
07

Registry details

Key details

Study ID
NCT05128825
Lead sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Responsible party
Sponsor
First posted
Nov 22, 2021
Start date
Feb 17, 2022
Primary completion
Dec 1, 2026 (estimated)
Completion
Jun 30, 2027 (estimated)
Last update
Sep 29, 2026

Study contacts

Project Director
Contact
medicalaffairs@zentalis.com
858.263.4333

Oversight

FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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