A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer

Phase 2

Recruiting

• Conditions: High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer
• Interventions: Drug: azenosertib

• Registration Number: NCT05128825
• Lead Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Brief Summary

This is a multi-part Phase 2 study to evaluate the efficacy and safety of azenosertib (ZN-c3) in subjects with Platinum-Resistant, High-Grade Serous Ovarian, Fallopian Tube, or Primary Peritoneal Cancer. Part 2 of the study will be conducted in subjects whose tumors are Cyclin E1 positive as determined by central review using the Sponsor's investigational clinical trial assay.

Detailed Description

A Phase 2 study to evaluate the efficacy and safety of azenossertib (ZN-c3) 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. By inhibiting WEE1, azenosertib enables cell cycle progression, despite high levels of DNA damage, thereby resulting in the accumulation of DNA damage leading to mitotic catastrophe and cancer cell death.

The study consists of two parts:

Part 1: All comers, no biomarker status required (completed enrollment)

Part 2: Cyclin E1 positive protein expression required

Study Timeline

• Study First Submitted: 2021-10-28
• Study First Submitted QC: 2021-11-09
• Study First Posted: 2021-11-22
• Study Start: 2022-02-17
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-16
• Last Update Posted: 2025-05-21
• Primary Completion: 2026-12-01
• Study Completion: 2027-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 170

Inclusion Criteria

1. Age ≥18 years

2. High-grade serous ovarian, fallopian tube or primary peritoneal cancer

3. Tumor testing (archival acceptable) confirms a positive Cyclin E1 protein status result determined by IHC using the Sponsor's investigational clinical trial assay

4. Prior therapy:

   1. Subjects 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

5. Measurable disease per RECIST Version 1.1.

6. Adequate hematologic and organ function, as defined in protocol

7. ECOG 0-1

Exclusion Criteria

1. Primary platinum-refractory disease

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

   1. Major surgery within 28 days
   2. Hospitalization within 14 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).
   7. Inability to discontinue treatment prescription or non-prescription drugs, or to discontinue consumption of food and herbal supplements that are strong or moderate CYP3A inhibitors and inducers or P-gp inhibitors at least 14 days prior to C1D1.

3. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, PKMYT1 inhibitor, or CHK1/2 inhibitor.

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

   1. Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
   2. Myocardial impairment resulting in heart failure (NYHA Class II-IV)
   3. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or may interfere with interpretation of study results
   4. Acute kidney injury requiring intervention or intravenous fluid in the last 14 days or presence of indwelling urinary catheter or percutaneous nephrostomy.
   5. Significant gastrointestinal abnormalities, including an inability to take oral medication, requirement for intravenous 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.
   6. 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 C1D1
   7. Any evidence of bowel obstruction as determined by air/fluid levels on computed tomography (CT scan, recent hospitalization for small bowel obstruction within 3 months prior to C1D1, or recurrent paracentesis or thoracentesis within 6 weeks prior to C1D1.

5. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).

6. Pregnant or lactating female subject or female subject of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.

7. 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, non-melanoma skin carcinoma, Stage 1 uterine cancer, or other malignancies with an expected curative outcome.

8. Subjects who are known to be immunocompromised or HIV-positive on highly active anti-retroviral therapy.

9. Subjects with known active hepatitis B or hepatitis C infection.

10. Individuals who are judged by the Investigator to be unsuitable as study subjects.

11. Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1a/1b (Completed Enrollment)	azenosertib	Azenosertib 400mg administered on a 5 days on, 2 days off intermittent schedule.
Part 2a: Arm 1	azenosertib	Azenosertib 400mg administered on a 5 days on, 2 days off intermittent schedule
Part 2a: Arm 2	azenosertib	Azenosertib 300mg administered on a 5 days on, 2 days off intermittent schedule
Part 2b	azenosertib	Azenosertib at the dose selected in Part 2a administered on a 5 days on, 2 days off intermittent schedule

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2]	Up to approximately 12 months from the enrollment of the last subject	Participants who achieve partial response (PR) or complete response (CR) per RECIST v1.1 criteria.

Secondary Outcome Measures

Name	Time	Method
Duration of response (DOR) defined by RECIST v1.1 [Part 2]	Up to approximately 12 months from the enrollment of the last subject	Time from the date of first documented response (CR or PR that is subsequently confirmed per RECIST v1.1) until the date of progressive disease (PD) or death.
Progression free survival (PFS) defined by RECIST v1.1 [Part 2]	Up to approximately 12 months from the enrollment of the last subject	Time from the date of first dose until the date of PD or death.
Clinical Benefit Rate (CBR) defined by RECIST v1.1 [Part 2]	Up to approximately 12 months from the enrollment of the last subject	The percentage of participants who have at least 1 confirmed response of CR or PR, or stable disease for at least 16 weeks before any evidence of progression.
CA-125 response by GCIG criteria [Part 2]	Up to approximately 12 months from the enrollment of the last subject	The GCIG CA-125 response was defined as at least 50% reduction in CA-125 levels from baseline.
Number of Subjects experiencing treatment emergent adverse events (TEAEs) [Part 2]	Up to approximately 12 months from the enrollment of the last subject

Trial Locations

Locations (42)

Site 0228 - Corewell Health Medical Group West; 🇺🇸 Grand Rapids, Michigan, United States

Site 0170-USA Mitchell Cancer Institute; 🇺🇸 Mobile, Alabama, United States

Site 0143 - HonorHealth; 🇺🇸 Phoenix, Arizona, United States

Site 0258 - UC San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Site 0287 - Ridley Tree Cancer Center; 🇺🇸 Santa Barbara, California, United States

Site 0135 - Rocky Mountain Cancer Centers; 🇺🇸 Lone Tree, Colorado, United States

Site 0239 - Florida Cancer Specialists - East; 🇺🇸 Daytona Beach, Florida, United States

Site 0173 - Mount Sinai Medical Center; 🇺🇸 Miami Beach, Florida, United States

Site 0236 - Memorial Health; 🇺🇸 Savannah, Georgia, United States

Site 0284 - Community Health Network; 🇺🇸 Indianapolis, Indiana, United States

Site 0251 - Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Site 0146 - Maryland Oncology Hematology, PA; 🇺🇸 Rockville, Maryland, United States

Site 0221 - Tufts Medical Center - PPDS; 🇺🇸 Boston, Massachusetts, United States

Site 0307 - Lahey Hospital and Medical Center; 🇺🇸 Burlington, Massachusetts, United States

Site 0288 - Minnesota Oncology Hematology - Maplewood; 🇺🇸 Maplewood, Minnesota, United States

Site 0226 - CoxHealth; 🇺🇸 Springfield, Missouri, United States

Site 0317 - Nebraska Methodist Hospital; 🇺🇸 Omaha, Nebraska, United States

Site 0213 - Center of Hope; 🇺🇸 Reno, Nevada, United States

Site 0231 - Northwell Health Cancer Institute; 🇺🇸 Manhasset, New York, United States

Site 0259 - Duke Cancer Center; 🇺🇸 Durham, North Carolina, United States

Site 0147 - Trihealth Cancer Institute - Harold and Eugen; 🇺🇸 Cincinnati, Ohio, United States

Site 0263 - Baystate Medical Center; 🇺🇸 Springfield, Massachusetts, United States

Site 0243 - Mark H Zangmeister Cancer Center; 🇺🇸 Columbus, Ohio, United States

Site 0214-Ohio State University Comprehensive Cancer Center; 🇺🇸 Hilliard, Ohio, United States

Site 0316 - Oncology Associates of Oregon, P.C.; 🇺🇸 Eugene, Oregon, United States

Site 0232 - University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Site 0277 - Alliance Cancer Specialist, PC; 🇺🇸 Wynnewood, Pennsylvania, United States

Site 0132 - Avera Cancer Institute; 🇺🇸 Sioux Falls, South Dakota, United States

Site 0203 - Texas Oncology; 🇺🇸 Tyler, Texas, United States

Site 0295 - Virginia Oncology Associates; 🇺🇸 Chesapeake, Virginia, United States

Site 3614 - Institut de Cancerologie de l'oust; 🇫🇷 Saint-Herblain, Pays de la Loire, France

Site 3608 - Hospices Civils de Lyon - Hôpital Lyon Sud; 🇫🇷 Pierre-Bénite, Rhône, France

Site 2715 - Icon Cancer Centre - Chermside; 🇦🇺 Brisbane, Queensland, Australia

Site 2707 - Mater Brisbane; 🇦🇺 South Brisbane, Queensland, Australia

Site 2709 - Icon Cancer Research Adelaide; 🇦🇺 Adelaide, South Australia, Australia

Site 2702 - Burnside War Memorial Hospital - The Brian Fricker Oncology Centre; 🇦🇺 Toorak Gardens, South Australia, Australia

Site 2701 - Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Site 2717 - St John of God Hospital Subiaco; 🇦🇺 Subiaco, Western Australia, Australia

Site 3616 - Centre Antoine Lacassagne; 🇫🇷 Nice, Alpes-Maritimes, France

Site 2405 - Centrum Badan Klinicznych JCI; 🇵🇱 Krakow, Malopolskie, Poland

Site 3602 - Centre Oscar Lambret; 🇫🇷 Lille, Nord, France

Site 3604 - Institut Gustave Roussy; 🇫🇷 Villejuif, France