A Study of Azenosertib (ZN-c3) Versus Investigator's Choice Chemotherapy in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression (ASPENOVA)

May 15, 2026 updated by: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

A Randomized, Open-Label Phase 3 Study of Azenosertib Versus Investigator's Choice of Chemotherapy in Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression

This is a randomized, Phase 3 trial designed to evaluate the efficacy and safety of azenosertib compared to Investigator's choice of chemotherapy in subjects with platinum-resistant ovarian cancer whose tumors are positive for cyclin E1 protein expression.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

A Phase 3 study to evaluate the efficacy, safety, and overall clinical benefit of azenosertib (ZN-c3) compared with Investigator's choice of chemotherapy 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. In HGSOC, high Cyclin E1 protein drives replication stress and increases tumor reliance on WEE1-mediated G2/M checkpoint control. Treating tumor cells with azenosertib promotes premature cell cycle progression leading to increased replication stress and accumulation of DNA damage pushing cells to mitotic catastrophe resulting in tumor cell death.

Study Type

Interventional

Enrollment (Estimated)

420

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Australia
      • Nedlands, Australia, 6009
        • Not yet recruiting
        • Site 1103
    • New South Wales
      • Randwick, New South Wales, Australia, 2031
        • Not yet recruiting
        • Site 1101
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Not yet recruiting
        • Site 1102
  • Belgium
      • Brussels, Belgium, 1020
        • Not yet recruiting
        • Site 3002
      • Leuven, Belgium, 3000
        • Not yet recruiting
        • Site 3001
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Not yet recruiting
        • Site 0201
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
        • Not yet recruiting
        • Site 0204
      • Montreal, Quebec, Canada, H2X 0C1
        • Not yet recruiting
        • Site 0203
      • Sherbrooke, Quebec, Canada, J1H 5N4
        • Not yet recruiting
        • Site 0202
  • France
      • Besançon, France, 25000
        • Not yet recruiting
        • Site 3508
      • Brest, France, 29609
        • Not yet recruiting
        • Site 3502
      • Dijon, France, 21079
        • Not yet recruiting
        • Site 3507
      • Lyon, France, 69373
        • Not yet recruiting
        • Site 3504
      • Paris, France, 75014
        • Not yet recruiting
        • Site 3503
      • Pierre-Bénite, France, 69495
        • Not yet recruiting
        • Site 3501
      • Saint-Herblain, France, 44805
        • Not yet recruiting
        • Site 3509
      • Strasbourg, France, 67098
        • Not yet recruiting
        • Site 3505
      • Villejuif, France, 94805
        • Not yet recruiting
        • Site 3506
  • Germany
      • Berlin, Germany, D-13353
        • Not yet recruiting
        • Site 3602
      • Dresden, Germany, 01307
        • Not yet recruiting
        • Site 3601
  • Ireland
      • Cork, Ireland, T12 DC4A
        • Not yet recruiting
        • Site 3703
      • Dublin, Ireland, D08 NYH1
        • Not yet recruiting
        • Site 3702
  • Italy
      • Bologna, Italy, 40138
        • Not yet recruiting
        • Site 3801
      • Milan, Italy, 20132
        • Not yet recruiting
        • Site 3805
      • Milan, Italy, 20141
        • Not yet recruiting
        • Site 3804
      • Milan, Italy, 20159
        • Not yet recruiting
        • Site 3803
      • Naples, Italy, 80131
        • Not yet recruiting
        • Site 3802
      • Prato, Italy, 59100
        • Not yet recruiting
        • Site 3807
      • Rome, Italy, 00168
        • Not yet recruiting
        • Site 3806
  • Poland
      • Krakow, Poland, 30-348
        • Not yet recruiting
        • Site 4006
      • Lodz, Poland, 93-338
        • Not yet recruiting
        • Site 4001
      • Poznan, Poland, 61-848
        • Not yet recruiting
        • Site 4004
      • Szczecin, Poland, 70-111
        • Not yet recruiting
        • Site 4003
  • South Korea
      • Daegu, South Korea, 42601
        • Not yet recruiting
        • Site 1203
      • Goyang-si, South Korea, 10408
        • Not yet recruiting
        • Site 1206
      • Seoul, South Korea, 03080
        • Not yet recruiting
        • Site 1202
      • Seoul, South Korea, 03722
        • Not yet recruiting
        • Site 1205
      • Seoul, South Korea, 06273
        • Not yet recruiting
        • Site 1204
      • Seoul, South Korea, 06351
        • Not yet recruiting
        • Site 1201
  • Spain
      • Barcelona, Spain, 08028
        • Not yet recruiting
        • Site 4201
      • Barcelona, Spain, 08041
        • Not yet recruiting
        • Site 4205
      • Madrid, Spain, 28034
        • Not yet recruiting
        • Site 4202
      • Madrid, Spain, 28040
        • Not yet recruiting
        • Site 4206
      • Málaga, Spain, 29011
        • Not yet recruiting
        • Site 4203
      • Vigo, Spain, 36212
        • Not yet recruiting
        • Site 4204
  • Taiwan
      • Taichung, Taiwan, 40705
        • Not yet recruiting
        • Site 1301
      • Taipei, Taiwan, 11217
        • Not yet recruiting
        • Site 1302
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85016
        • Not yet recruiting
        • Site 0107
    • California
      • Antioch, California, United States, 94531
        • Not yet recruiting
        • Site 0110
      • San Francisco, California, United States, 94109
        • Not yet recruiting
        • Site 0115
      • Torrance, California, United States, 90505
        • Recruiting
        • Site 0101
    • New Jersey
      • Camden, New Jersey, United States, 08103
        • Not yet recruiting
        • Site 0111
    • Ohio
      • Columbus, Ohio, United States, 43026
        • Not yet recruiting
        • Site 0108
    • Oregon
      • Portland, Oregon, United States, 97210
        • Not yet recruiting
        • Site 0105
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Not yet recruiting
        • Site 0109
      • Philadelphia, Pennsylvania, United States, 19111
        • Not yet recruiting
        • Site 0113
      • Willow Grove, Pennsylvania, United States, 19090
        • Not yet recruiting
        • Site 0114
    • South Dakota
      • Sioux Falls, South Dakota, United States, 57105
        • Not yet recruiting
        • Site 0112

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Female age ≥ 18 years
  2. High-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer
  3. Measurable disease per RECIST Version 1.1
  4. Eastern Cooperative Oncology Group (ECOG) performance status score 0-1
  5. The subject's tumor tissue must be positive for cyclin E1 protein expression per the Sponsor's clinically validated cyclin E1 IHC investigational, in vitro diagnostic assay

  6. Prior Therapy:

    1. Subject must have platinum-resistant disease
    2. One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
    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
  7. Adequate hematologic and organ function during the screening period

Exclusion Criteria:

  1. 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, nonmelanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome.
  2. Subjects with primary platinum-refractory disease.
  3. Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or (PKMYT1) inhibitor for PROC.

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

    1. Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
    2. Acute kidney injury requiring intervention, or presence of indwelling urinary catheter or percutaneous nephrostomy.
    3. Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for IV 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.
    4. Any evidence of small bowel obstruction as determined by air/fluid levels on computed tomography (CT) scan, recent hospitalization for small bowel obstruction within 3 months before randomization, or recurrent paracentesis or thoracentesis within 6 weeks before randomization.
    5. 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 randomization
    6. Myocardial impairment of any cause resulting in heart failure by New York Heart Association criteria (Class II, III or IV).
    7. Medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results

  5. Any of the following treatment interventions within the specified time frame before randomization:

    1. Hospitalization within 14 days
    2. Major surgery within 28 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)
  6. Inability to discontinue treatment with prescription or nonprescription drugs that are prohibited per protocol.
  7. Inability to discontinue consumption of food and herbal supplements that are prohibited per protocol
  8. Prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.
  9. Unresolved toxicity of Grade > 1 attributed to any prior therapies (excluding Grade ≤ 2 neuropathy, alopecia, or skin pigmentation).
  10. Subjects who are immunocompromised or HIV-positive on highly active anti-retroviral therapy
  11. Subjects with known active hepatitis B or hepatitis C infection
  12. Individuals who are judged by the Investigator to be unsuitable as study subjects

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Experimental: Arm C Investigator's choice of chemotherapy at the dose defined by the protocol
Drug: Investigator's choice of Chemotherapy

The investigator will select the chemotherapy in accordance with the protocol defined requirements. The possible choices as defined by the protocol:

  • Paclitaxel
  • Gemcitabine
  • Pegylated liposomal doxorubicin (PLD)
  • Topotecan

The selected chemotherapy will be administered intravenously
Experimental: Arm A Azenosertib 400 mg administered daily on a 5 days on, 2 days off intermittent schedule
Drug: Azenosertib
Azenosertib 400 mg will be administered orally.
Other Names:
  • ZN-c3

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Time from randomization to the first documented tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.
Up to approximately 24 months from the enrollment of the last subject

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall survival
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Time from randomization until death due to any cause
Up to approximately 24 months from the enrollment of the last subject
PFS per RECIST 1.1 as assessed by blinded independent central review (ICR)
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Time from randomization to the first documented tumor progression (per RECIST v1.1) or death from any cause, whichever occurs first.
Up to approximately 24 months from the enrollment of the last subject
Objective Response Rate (ORR) per RECIST v1.1 and assessed by Investigator
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Proportion of patients who attain a partial response (PR) or complete response (CR) per RECIST v1.1
Up to approximately 24 months from the enrollment of the last subject
Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire score (EORTC QLQ)-Core 30 (C30) at each post baseline visit
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Assess changes over time in cancer-specific and patient-reported outcome instruments assessing global health status/quality of life, functional domains, and symptom burden.
Up to approximately 24 months from the enrollment of the last subject
Change from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire score (EORTC QLQ)-OV28 at each post baseline visit
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Assess changes over time in cancer-specific and patient-reported outcome instruments assessing global health status/quality of life, functional domains, and symptom burden.
Up to approximately 24 months from the enrollment of the last subject
Change from baseline in EQ-5D-5L score at each post baseline visit
Time Frame: Up to approximately 24 months from the enrollment of the last subject
Assess changes over time in cancer-specific and patient-reported outcome instruments assessing global health status/quality of life, functional domains, and symptom burden.
Up to approximately 24 months from the enrollment of the last subject
Number of Subjects experiencing treatment emergent adverse events (TEAEs)
Time Frame: Up to approximately 24 months and 30 days from the enrollment of the last subject
Assess adverse events occurring for the first time or worsening of a pre-existing event during the treatment period until 30 days after the last dose of study drug
Up to approximately 24 months and 30 days from the enrollment of the last subject

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Collaborators

GOG Foundation
European Network of Gynaecological Oncological Trial Groups (ENGOT)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 17, 2026

Primary Completion (Estimated)

May 31, 2028

Study Completion (Estimated)

April 30, 2030

Study Registration Dates

First Submitted

March 26, 2026

First Submitted That Met QC Criteria

April 16, 2026

First Posted (Actual)

April 22, 2026

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 15, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZN-c3-020
  • GOG-3147 (Other Identifier: GOG Foundation, Inc.)
  • ENGOT-ov109 (Other Identifier: ENGOT)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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