A Study of Azenosertib (ZN-c3) in Women With Recurrent or Persistent Uterine Serous Carcinoma

A Phase 2 Open-Label, Multicenter Study to Evaluate Efficacy and Safety of ZN-c3 in Adult Women With Recurrent or Persistent Uterine Serous Carcinoma

This is a Phase 2 study to evaluate the clinical activity and safety of ZN-c3 (azenosertib) in adult women with recurrent or persistent uterine serous carcinoma (USC).

Study Overview

• Status: Completed
• Conditions: Uterine Serous Carcinoma
• Intervention / Treatment: Drug: Azenosertib

Detailed Description

This is a Phase 2 open-label, multicenter study to evaluate the clinical activity and safety of ZN-c3 (also known as azenosertib; KP-2638) in adult women with recurrent or persistent uterine serous carcinoma (USC).

• Study Type: Interventional
• Enrollment (Actual): 92
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Concord Repatriation General Hospital
    • St Leonards, New South Wales, Australia, 2065
      • Northern Cancer Institute
  • Queensland
    • Brisbane, Queensland, Australia, 4032
      • Icon Cancer Centre- Chermside
    • Brisbane, Queensland, Australia, 4101
      • Mater Cancer Care Centre, Mater Misericordiae Limited
  • South Australia
    • Toorak Gardens, South Australia, Australia, 6065
      • Burnside War Memorial Hospital
  • Victoria
    • Malvern, Victoria, Australia, 3144
      • Cabrini Hospital Malvern
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Sir Charles Gairdner Hospital
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Québec, Quebec, Canada, G1R 3S1
      • Chu de Quebec-Universite
• Georgia
  • Tbilisi, Georgia, 0112
    • Acad. Fridon Todua Medical Center
  • Tbilisi, Georgia, 0144
    • LTD Innova Medical Center
  • Tbilisi, Georgia, 0160
    • LTD TIM-Tbilisi Innova of Medicine
  • Adjara
    • Batumi, Adjara, Georgia, 6000
      • LTD High Technology Hospital Medcenter
  • Kvemo Kartli
    • Rustavi, Kvemo Kartli, Georgia, 3700
      • Rustavi Clinic
• United States
  • Alaska
    • Anchorage, Alaska, United States, 99508
      • Alaska Women's Cancer Care
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Honor Health
    • Tucson, Arizona, United States, 85719
      • Banner University Medical Center Tucson
    • Tucson, Arizona, United States, 85711
      • Arizona Oncology Associates Wilmot HOPE
  • California
    • Orange, California, United States, 92868
      • University of California Irvine Medical Center
    • San Francisco, California, United States, 94158
      • University of California San Francisco at Mission Bay
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Sarasota, Florida, United States, 34239
      • Sarasota Memorial Hospital
    • Tampa, Florida, United States, 33606
      • University of South Florida
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Northside Hospital
    • Augusta, Georgia, United States, 30912
      • Georgia Cancer Center at Augusta University
  • Illinois
    • Evanston, Illinois, United States, 60208
      • Northwestern University
  • Maryland
    • Annapolis, Maryland, United States, 21401
      • Maryland Oncology Hematology
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Oakland Medical Group
    • Grand Rapids, Michigan, United States, 49503
      • Corewell Health
    • Sterling, Michigan, United States, 48659
      • Revive Clinical Research
  • Missouri
    • Kansas City, Missouri, United States, 64132
      • HCA Midwest Health Kansas City Research
  • Nevada
    • Reno, Nevada, United States, 89511
      • Center of Hope
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Optimum Clinical Research Group- Women's Oncology
  • New York
    • Hawthorne, New York, United States, 10532
      • Westchester Medical Center
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • University of Cincinnati
    • Cincinnati, Ohio, United States, 45242
      • Oncology Hematology Care
    • Cincinnati, Ohio, United States, 45242
      • TriHealth Cancer Institute
    • Columbus, Ohio, United States, 43210
      • Ohio State University James Cancer Hospital
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Peggy and Charles Stephenson Cancer Center
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Willamette Valley Cancer Institute
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97227
      • Northwest Cancer Specialists
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37236
      • Ascension St. Thomas Midtown Hospital
  • Texas
    • Austin, Texas, United States, 78705
      • Texas Oncology Austin
    • Fort Worth, Texas, United States, 76104
      • Texas Oncology Fort Worth Cancer Center
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
    • Houston, Texas, United States, 77089
      • Texas Oncology Gulf Coast
    • San Antonio, Texas, United States, 78240
      • Texas Oncology San Antonio
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Cancer Center
    • Richmond, Virginia, United States, 23298
      • VCU Health System
    • Warrenton, Virginia, United States, 20186
      • Virginia Cancer Specialists
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

1. Females ≥18 years of age at the time of informed consent.

2. Histologically confirmed recurrent or persistent USC for which no other proven effective treatment options are available or any available standard of care therapy was not tolerated or was refused by the subject.

   • Subjects with endometrial carcinoma of mixed histology where the serous component comprises at least 5% of the tumor will be considered eligible.
   • Subjects with carcinosarcomas (even if there is a serous component) are not eligible.
3. Measurable disease per RECIST Guideline Version 1.1

4. Required prior therapy for endometrial cancer:

   1. Treatment with a platinum-based chemotherapy regimen.
   2. Treatment with a PD-(L)1 inhibitor
   3. Known HER2-positive tumors: Treatment with at least 1 HER2-targeted therapy, except for subjects who are not clinically eligible.
5. Adequate hematologic and organ function

EXCLUSION CRITERIA

1. Any of the following treatment interventions within the specified time frame prior to C1D1:

   1. Major surgery within 28 days
   2. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter).
   3. Radiation therapy within 21 days;
   4. Autologous or allogeneic stem cell transplant within 3 months.
   5. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
2. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, or CHK1/2 inhibitor for USC.
3. A serious illness or medical condition(s) including, but not limited to: Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Azenosertib Single Agent; Azenosertib (ZN-c3) taken orally with food	Drug: Azenosertib; Azenosertib is an investigational drug.; Other Names: ZN-c3

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate as defined by the revised RECIST v1.1 as assessed by ICR	To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC	2 years
Frequency and severity of TEAEs	To determine the safety and tolerability of ZN-c3 in subjects with recurrent or persistent USC.	2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.	To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules	2 years
Duration of Response as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.	To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules	2 years
Progression Free Survival as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.	To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules	2 years
Clinical Benefit Rate as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.	To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules	2 years
Time To Response as defined by the revised RECIST v1.1. and assessed by ICR and the Investigator.	To investigate the antitumor activity of ZN-c3 in subjects with recurrent or persistent USC at different doses/schedules	2 years

Collaborators and Investigators

• Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
• Investigators: Study Director: Project Director, K-Group Beta (A wholly owned subsidiary of Zentalis Pharmaceuticals)

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Actual): October 22, 2025
• Study Completion (Actual): October 22, 2025

Study Registration Dates

• First Submitted: March 18, 2021
• First Submitted That Met QC Criteria: March 22, 2021
• First Posted (Actual): March 24, 2021

Study Record Updates

• Last Update Posted (Actual): March 18, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: endometrium; uterus; endometrial; uterine; Uterine Serous Carcinoma; serous; serous carcinoma; wee1; Wee-1; usc
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Carcinoma; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Cystadenocarcinoma, Serous
• Other Study ID Numbers: ZN-c3-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No