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

Last updated: April 18, 2025
Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Overall Status: Active - Recruiting

Phase

2

Condition

Malignant Ascites

Peritoneal Cancer

Digestive System Neoplasms

Treatment

ZN-c3

azenosertib

Clinical Study ID

NCT05128825
ZN-c3-005
  • Ages > 18
  • Female

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.

Eligibility Criteria

Inclusion

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 statusresult determined by IHC using the Sponsor's investigational clinical trial assay

  4. Prior therapy:

  5. Subjects must have platinum-resistant disease

  6. One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted,if prior mirvetuximab)

  7. Prior bevacizumab treatment is required, if eligible per standard of care

  8. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, ifeligible per standard of care

  9. Prior mirvetuximab treatment is required, if eligible per standard of care

  10. Measurable disease per RECIST Version 1.1.

  11. Adequate hematologic and organ function, as defined in protocol

  12. ECOG 0-1

Exclusion

Exclusion Criteria:

  1. Primary platinum-refractory disease

  2. Any of the following treatment interventions within the specified time frame priorto C1D1:

  3. Major surgery within 28 days

  4. Hospitalization within 14 days

  5. Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter);

  6. Radiation therapy within 21 days;

  7. Autologous or allogeneic stem cell transplant within 3 months.

  8. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).

  9. Inability to discontinue treatment prescription or non-prescription drugs, orto discontinue consumption of food and herbal supplements that are strong ormoderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 daysprior to C1D1.

  10. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, PKMYT1inhibitor, or CHK1/2 inhibitor.

  11. A serious illness or medical condition(s) including, but not limited to:

  12. Clinically or radiographically unstable brain metastases or leptomeningealdisease that requires immediate treatment. Subjects with asymptomatic brainmetastases are eligible.

  13. Myocardial impairment resulting in heart failure (NYHA Class II-IV)

  14. Severe acute or chronic medical or psychiatric condition or laboratoryabnormality that may increase risk associated with study participation or mayinterfere with interpretation of study results

  15. Acute kidney injury requiring intervention or intravenous fluid in the last 14days or presence of indwelling urinary catheter or percutaneous nephrostomy.

  16. Significant gastrointestinal abnormalities, including an inability to take oralmedication, requirement for intravenous alimentation, active peptic ulcer,chronic diarrhea or vomiting considered to be clinically significant in thejudgment of the Investigator, or prior surgical procedures affectingabsorption.

  17. Active, uncontrolled infection. Subjects with an infection receiving treatment (antibiotic, antifungal, or antiviral) must have completed such treatment andthe infection must be considered controlled/resolved (and afebrile) by theInvestigator for at least 7 days before C1D1

  18. Any evidence of bowel obstruction as determined by air/fluid levels on computedtomography (CT scan, recent hospitalization for small bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6weeks prior to C1D1.

  19. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).

  20. Pregnant or lactating female subject or female subject of childbearing potential whohas a positive serum pregnancy test within 14 days prior to C1D1.

  21. History of another malignancy in the previous 2 years, unless cured by surgery aloneand continuously disease free. Exceptions include appropriately treated carcinoma insitu of the cervix, non-melanoma skin carcinoma, Stage 1 uterine cancer, or othermalignancies with an expected curative outcome.

  22. Subjects who are known to be immunocompromised or HIV-positive on highly activeanti-retroviral therapy.

  23. Subjects with known active hepatitis B or hepatitis C infection.

  24. Individuals who are judged by the Investigator to be unsuitable as study subjects.

  25. Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.

Study Design

Total Participants: 170
Treatment Group(s): 2
Primary Treatment: ZN-c3
Phase: 2
Study Start date:
February 17, 2022
Estimated Completion Date:
June 30, 2027

Study 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

Connect with a study center

  • Site 2715 - Icon Cancer Centre - Chermside

    Brisbane, Queensland 4032
    Australia

    Site Not Available

  • Site 2707 - Mater Brisbane

    South Brisbane, Queensland 4101
    Australia

    Site Not Available

  • Site 2709 - Icon Cancer Research Adelaide

    Adelaide, South Australia 5037
    Australia

    Site Not Available

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

    Toorak Gardens, South Australia 5065
    Australia

    Site Not Available

  • Site 2701 - Sir Charles Gairdner Hospital

    Nedlands, Western Australia 6009
    Australia

    Site Not Available

  • Site 2717 - St John of God Hospital Subiaco

    Subiaco, Western Australia 6008
    Australia

    Site Not Available

  • Site 3616 - Centre Antoine Lacassagne

    Nice, Alpes-Maritimes 06100
    France

    Site Not Available

  • Site 3602 - Centre Oscar Lambret

    Lille, Nord 59000
    France

    Site Not Available

  • Site 3614 - Institut de Cancerologie de l'oust

    Saint-Herblain, Pays de la Loire 44800
    France

    Site Not Available

  • Site 3608 - Hospices Civils de Lyon - Hôpital Lyon Sud

    Pierre-Bénite, Rhône 69310
    France

    Site Not Available

  • Site 3614 - Institut de Cancerologie de l'oust - Centre Rene Gauducheau

    Saint-Herblain, 44805
    France

    Active - Recruiting

  • Site 3604 - Institut Gustave Roussy

    Villejuif, 94800
    France

    Site Not Available

  • Site 2405 - Centrum Badan Klinicznych JCI

    Krakow, Malopolskie 30-348
    Poland

    Site Not Available

  • Site 0170-USA Mitchell Cancer Institute

    Mobile, Alabama 36604
    United States

    Active - Recruiting

  • Site 0143 - HonorHealth

    Phoenix, Arizona 85016
    United States

    Site Not Available

  • Site 0258 - UC San Diego Moores Cancer Center

    La Jolla, California 92037
    United States

    Active - Recruiting

  • Site 0124 - University of California Irvine

    Orange, California 92697
    United States

    Site Not Available

  • Site 0287 - Ridley Tree Cancer Center

    Santa Barbara, California 93105
    United States

    Site Not Available

  • Site 0135

    Denver, Colorado 80218
    United States

    Site Not Available

  • Site 0135 - Rocky Mountain Cancer Centers

    Lone Tree, Colorado 80218
    United States

    Site Not Available

  • Site 0239 - Florida Cancer Specialists - East

    Daytona Beach, Florida 32117
    United States

    Active - Recruiting

  • Site 0291 - CRC Cancer Centers of Brevard

    Melbourne, Florida 32935
    United States

    Site Not Available

  • Site 0173 - Mount Sinai Medical Center

    Miami Beach, Florida 33140
    United States

    Active - Recruiting

  • Site 0181 - Sarasota Memorial Health Care System

    Sarasota, Florida 34240
    United States

    Site Not Available

  • Site 0236 - Memorial Health

    Savannah, Georgia 31404
    United States

    Active - Recruiting

  • Site 0159 - North Shore University Health System

    Evanston, Illinois 60201
    United States

    Site Not Available

  • Site 0261 - Carle Cancer Institute

    Urbana, Illinois 61801
    United States

    Site Not Available

  • Site 0284 - Community Health Network

    Indianapolis, Indiana 46250
    United States

    Active - Recruiting

  • Site 0313 - Beacon Health System

    South Bend, Indiana 46601
    United States

    Site Not Available

  • Site 0251 - Norton Cancer Institute

    Louisville, Kentucky 40202
    United States

    Active - Recruiting

  • Site 0146

    Germantown, Maryland 20876
    United States

    Site Not Available

  • Site 0146 - Maryland Oncology Hematology, PA

    Rockville, Maryland 20876
    United States

    Site Not Available

  • Site 0221 - Tufts Medical Center - PPDS

    Boston, Massachusetts 02111
    United States

    Active - Recruiting

  • Site 0307 - Lahey Hospital and Medical Center

    Burlington, Massachusetts 01805
    United States

    Site Not Available

  • Site 0263 - Baystate Medical Center

    Springfield, Massachusetts 01199
    United States

    Site Not Available

  • Site 0288 - Minnesota Oncology Hematology - Maplewood

    Maplewood, Minnesota 55109
    United States

    Active - Recruiting

  • Site 0310 - St. Louis Cancer Care LLP

    Bridgeton, Missouri 63044
    United States

    Site Not Available

  • Site 0157 - Mercy Hospital Saint Louis

    Saint Louis, Missouri 63141
    United States

    Site Not Available

  • Site 0226 - CoxHealth

    Springfield, Missouri 65807
    United States

    Site Not Available

  • Site 0317 - Nebraska Methodist Hospital

    Omaha, Nebraska 68114
    United States

    Site Not Available

  • Site 0213 - Center of Hope

    Reno, Nevada 89511
    United States

    Active - Recruiting

  • Site 0275 - Valley Hospital

    Paramus, New Jersey 07653
    United States

    Site Not Available

  • Site 0220 - Westchester Medical Center

    Hawthorne, New York 10532
    United States

    Site Not Available

  • Site 0231 - Northwell Health Cancer Institute

    Manhasset, New York 11030
    United States

    Site Not Available

  • Site 0176 - Columbia University Medical Center

    New York, New York 10032
    United States

    Site Not Available

  • Site 0259 - Duke Cancer Center

    Durham, North Carolina 27710
    United States

    Site Not Available

  • Site 0283 - Miami Valley Hospital South

    Centerville, Ohio 45459
    United States

    Site Not Available

  • Site 0147 - Trihealth Cancer Institute - Harold and Eugen

    Cincinnati, Ohio 45242
    United States

    Active - Recruiting

  • Site 0149 - University Hospitals Case Medical Center

    Cleveland, Ohio 44106
    United States

    Site Not Available

  • Site 0243 - Mark H Zangmeister Cancer Center

    Columbus, Ohio 43219
    United States

    Active - Recruiting

  • Site 0257 - Columbus NCORP

    Columbus, Ohio 43215
    United States

    Site Not Available

  • Site 0214-Ohio State University Comprehensive Cancer Center

    Hilliard, Ohio 43026
    United States

    Site Not Available

  • Site 0316 - Oncology Associates of Oregon, P.C.

    Eugene, Oregon 97401
    United States

    Site Not Available

  • Site 0262 - Lancaster General Hospital

    Lancaster, Pennsylvania 17602
    United States

    Site Not Available

  • Site 0232 - University of Pennsylvania

    Philadelphia, Pennsylvania 19104
    United States

    Active - Recruiting

  • Site 0277 - Alliance Cancer Specialist, PC

    Wynnewood, Pennsylvania 19096
    United States

    Site Not Available

  • Site 0260 - Monument Health Rapid City Hospital

    Rapid City, South Dakota 57701
    United States

    Site Not Available

  • Site 0132 - Avera Cancer Institute

    Sioux Falls, South Dakota 57105
    United States

    Active - Recruiting

  • Site 0293 - Texas Oncology - Abilene

    Abilene, Texas 79606
    United States

    Site Not Available

  • Site 0293 - Texas Oncology - Amarillo

    Amarillo, Texas 79106
    United States

    Site Not Available

  • Site 0145- Texas Oncology - Austin

    Austin, Texas 78745
    United States

    Site Not Available

  • Site 0142 - Texas Oncology - Baylor Charles A. Sammons Cancer Center

    Dallas, Texas 75246
    United States

    Site Not Available

  • Site 0227

    Houston, Texas 11030
    United States

    Site Not Available

  • Site 0201 - Texas Oncology

    McKinney, Texas 75071
    United States

    Site Not Available

  • Site 0203 - Texas Oncology

    Tyler, Texas 75702
    United States

    Site Not Available

  • Site 0318 - Utah Cancer Specialists

    Salt Lake City, Utah 84106
    United States

    Site Not Available

  • Site 0295 - Virginia Oncology Associates

    Chesapeake, Virginia 23320
    United States

    Site Not Available

  • Site 0269 - Oncology & Hematology Associates of Southwest Virginia, Inc.

    Roanoke, Virginia 24014
    United States

    Site Not Available

  • Site 0153 - University of Wisconsin Clinical Science Center

    Madison, Wisconsin 53792
    United States

    Site Not Available

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