Back to Trials
NCT07546500PHASE3Recruiting

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

Start Date

4/17/2026

Completion Date

4/30/2030

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.

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

Investigator's choice of Chemotherapy

DRUG

Azenosertib

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

Ovarian Cancer

Locations

Site 0107

Phoenix, Arizona 85016

United States

Site 0110

Antioch, California 94531

United States

Site 0115

San Francisco, California 94109

United States

Site 0101

Torrance, California 90505

United States

Site 0111

Camden, New Jersey 08103

United States

Site 0108

Columbus, Ohio 43026

United States

Site 0105

Portland, Oregon 97210

United States

Site 0109

Philadelphia, Pennsylvania 19104

United States

Site 0113

Philadelphia, Pennsylvania 19111

United States

Site 0114

Willow Grove, Pennsylvania 19090

United States

Site 0112

Sioux Falls, South Dakota 57105

United States

Site 1101

Randwick, New South Wales 2031

Australia

Site 1102

Adelaide, South Australia 5000

Australia

Site 1103

Nedlands, 6009

Australia

Site 3002

Brussels, 1020

Belgium

Site 3001

Leuven, 3000

Belgium

Site 0201

Toronto, Ontario M5G 2M9

Canada

Site 0204

Montreal, Quebec H1T 2M4

Canada

Site 0203

Montreal, Quebec H2X 0C1

Canada

Site 0202

Sherbrooke, Quebec J1H 5N4

Canada

Site 3508

Besançon, 25000

France

Site 3502

Brest, 29609

France

Site 3507

Dijon, 21079

France

Site 3504

Lyon, 69373

France

Site 3503

Paris, 75014

France

Site 3501

Pierre-Bénite, 69495

France

Site 3509

Saint-Herblain, 44805

France

Site 3505

Strasbourg, 67098

France

Site 3506

Villejuif, 94805

France

Site 3602

Berlin, D-13353

Germany

Site 3601

Dresden, 01307

Germany

Site 3703

Cork, T12 DC4A

Ireland

Site 3702

Dublin, D08 NYH1

Ireland

Site 3801

Bologna, 40138

Italy

Site 3805

Milan, 20132

Italy

Site 3804

Milan, 20141

Italy

Site 3803

Milan, 20159

Italy

Site 3802

Naples, 80131

Italy

Site 3807

Prato, 59100

Italy

Site 3806

Rome, 00168

Italy

Site 4006

Krakow, 30-348

Poland

Site 4001

Lodz, 93-338

Poland

Site 4004

Poznan, 61-848

Poland

Site 4003

Szczecin, 70-111

Poland

Site 1203

Daegu, 42601

South Korea

Site 1206

Goyang-si, 10408

South Korea

Site 1202

Seoul, 03080

South Korea

Site 1205

Seoul, 03722

South Korea

Site 1204

Seoul, 06273

South Korea

Site 1201

Seoul, 06351

South Korea

Site 4201

Barcelona, 08028

Spain

Site 4205

Barcelona, 08041

Spain

Site 4202

Madrid, 28034

Spain

Site 4206

Madrid, 28040

Spain

Site 4203

Málaga, 29011

Spain

Site 4204

Vigo, 36212

Spain

Site 1301

Taichung, 40705

Taiwan

Site 1302

Taipei, 11217

Taiwan