TrialPath
Recruiting

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

NCT07546500 · K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
In plain English

Click the button to translate this study into plain language — what it is, who qualifies, and what participation looks like.

Official title
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
About this study
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
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 design
Enrollment target: 420 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2026-04-17
Estimated completion: 2030-04-30
Last updated: 2026-05-19
Interventions
Drug: Investigator's choice of ChemotherapyDrug: Azenosertib
Primary outcomes
  • Progression free survival (PFS) per RECIST v1.1 as assessed by Investigator (Up to approximately 24 months from the enrollment of the last subject)
Sponsor
K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc · industry
With: European Network of Gynaecological Oncological Trial Groups (ENGOT), GOG Foundation
Contacts & investigators
ContactProject Director · contact · medicalaffairs@zentalis.com · 858.263.4333
All locations (58)
Site 0107Not Yet Recruiting
Phoenix, Arizona, United States
Site 0110Not Yet Recruiting
Antioch, California, United States
Site 0115Not Yet Recruiting
San Francisco, California, United States
Site 0101Recruiting
Torrance, California, United States
Site 0111Not Yet Recruiting
Camden, New Jersey, United States
Site 0108Not Yet Recruiting
Columbus, Ohio, United States
Site 0105Not Yet Recruiting
Portland, Oregon, United States
Site 0109Not Yet Recruiting
Philadelphia, Pennsylvania, United States
Site 0113Not Yet Recruiting
Philadelphia, Pennsylvania, United States
Site 0114Not Yet Recruiting
Willow Grove, Pennsylvania, United States
Site 0112Not Yet Recruiting
Sioux Falls, South Dakota, United States
Site 1101Not Yet Recruiting
Randwick, New South Wales, Australia
Site 1102Not Yet Recruiting
Adelaide, South Australia, Australia
Site 1103Not Yet Recruiting
Nedlands, Australia
Site 3002Not Yet Recruiting
Brussels, Belgium
Site 3001Not Yet Recruiting
Leuven, Belgium
Site 0201Not Yet Recruiting
Toronto, Ontario, Canada
Site 0204Not Yet Recruiting
Montreal, Quebec, Canada
Site 0203Not Yet Recruiting
Montreal, Quebec, Canada
Site 0202Not Yet Recruiting
Sherbrooke, Quebec, Canada
Site 3508Not Yet Recruiting
Besançon, France
Site 3502Not Yet Recruiting
Brest, France
Site 3507Not Yet Recruiting
Dijon, France
Site 3504Not Yet Recruiting
Lyon, France
Site 3503Not Yet Recruiting
Paris, France
Site 3501Not Yet Recruiting
Pierre-Bénite, France
Site 3509Not Yet Recruiting
Saint-Herblain, France
Site 3505Not Yet Recruiting
Strasbourg, France
Site 3506Not Yet Recruiting
Villejuif, France
Site 3602Not Yet Recruiting
Berlin, Germany
Site 3601Not Yet Recruiting
Dresden, Germany
Site 3703Not Yet Recruiting
Cork, Ireland
Site 3702Not Yet Recruiting
Dublin, Ireland
Site 3801Not Yet Recruiting
Bologna, Italy
Site 3805Not Yet Recruiting
Milan, Italy
Site 3804Not Yet Recruiting
Milan, Italy
Site 3803Not Yet Recruiting
Milan, Italy
Site 3802Not Yet Recruiting
Naples, Italy
Site 3807Not Yet Recruiting
Prato, Italy
Site 3806Not Yet Recruiting
Rome, Italy
Site 4006Not Yet Recruiting
Krakow, Poland
Site 4001Not Yet Recruiting
Lodz, Poland
Site 4004Not Yet Recruiting
Poznan, Poland
Site 4003Not Yet Recruiting
Szczecin, Poland
Site 1203Not Yet Recruiting
Daegu, South Korea
Site 1206Not Yet Recruiting
Goyang-si, South Korea
Site 1202Not Yet Recruiting
Seoul, South Korea
Site 1205Not Yet Recruiting
Seoul, South Korea
Site 1204Not Yet Recruiting
Seoul, South Korea
Site 1201Not Yet Recruiting
Seoul, South Korea
Site 4201Not Yet Recruiting
Barcelona, Spain
Site 4205Not Yet Recruiting
Barcelona, Spain
Site 4202Not Yet Recruiting
Madrid, Spain
Site 4206Not Yet Recruiting
Madrid, Spain
Site 4203Not Yet Recruiting
Málaga, Spain
Site 4204Not Yet Recruiting
Vigo, Spain
Site 1301Not Yet Recruiting
Taichung, Taiwan
Site 1302Not Yet Recruiting
Taipei, Taiwan
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 · TrialPath