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
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Phase
Phase 3
Started
2026-04-17
Last updated
2026-08-12
Condition(s) studied
Ovarian Cancer
Investigational drug(s) / intervention(s)
Investigator's choice of ChemotherapyAzenosertib
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
Azenosertib: Azenosertib 400 mg will be administered orally.
Study summary
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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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
Primary outcome measure(s)
Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator — 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.
Trial sites (59)
Facility
City
Region
Status
Site 0107
Phoenix
Arizona
Not Yet Recruiting
Site 0110
Antioch
California
Not Yet Recruiting
Site 0104
Beverly Hills
California
Recruiting
Site 0115
San Francisco
California
Not Yet Recruiting
Site 0101
Torrance
California
Recruiting
Site 0111
Camden
New Jersey
Not Yet Recruiting
Site 0108
Columbus
Ohio
Not Yet Recruiting
Site 0105
Portland
Oregon
Not Yet Recruiting
Site 0109
Philadelphia
Pennsylvania
Not Yet Recruiting
Site 0113
Philadelphia
Pennsylvania
Not Yet Recruiting
Site 0114
Willow Grove
Pennsylvania
Not Yet Recruiting
Site 0112
Sioux Falls
South Dakota
Not Yet Recruiting
Site 1101
Randwick
New South Wales
Not Yet Recruiting
Site 1102
Adelaide
South Australia
Recruiting
Site 1103
Nedlands
Australia
Not Yet Recruiting
Site 3002
Brussels
Belgium
Not Yet Recruiting
Site 3001
Leuven
Belgium
Not Yet Recruiting
Site 0201
Toronto
Ontario
Not Yet Recruiting
Site 0204
Montreal
Quebec
Not Yet Recruiting
Site 0203
Montreal
Quebec
Not Yet Recruiting
Site 0202
Sherbrooke
Quebec
Not Yet Recruiting
Site 3508
Besançon
France
Not Yet Recruiting
Site 3502
Brest
France
Not Yet Recruiting
Site 3507
Dijon
France
Not Yet Recruiting
Site 3504
Lyon
France
Not Yet Recruiting
Site 3503
Paris
France
Not Yet Recruiting
Site 3501
Pierre-Bénite
France
Not Yet Recruiting
Site 3509
Saint-Herblain
France
Not Yet Recruiting
Site 3505
Strasbourg
France
Not Yet Recruiting
Site 3506
Villejuif
France
Not Yet Recruiting
Site 3602
Berlin
Germany
Not Yet Recruiting
Site 3601
Dresden
Germany
Not Yet Recruiting
Site 3703
Cork
Ireland
Not Yet Recruiting
Site 3702
Dublin
Ireland
Not Yet Recruiting
Site 3801
Bologna
Italy
Not Yet Recruiting
Site 3805
Milan
Italy
Not Yet Recruiting
Site 3804
Milan
Italy
Not Yet Recruiting
Site 3803
Milan
Italy
Not Yet Recruiting
Site 3802
Naples
Italy
Not Yet Recruiting
Site 3807
Prato
Italy
Not Yet Recruiting
+ 19 more sites — see the full list on the official registry below.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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