azenosertib: Azenosertib (ZN-c3) will be administered orally.
Study 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.
Eligibility
Sex
FEMALE
Min age
18 Years
Max age
—
Healthy volunteers
No
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. Parts 2a and 2b: One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
3. Part 2c: Subjects with PROC may have 1 to 4 prior lines or regimens. Prior treatment in this cohort includes a weekly taxane regimen, either as single agent or in combination, per protocol
4. Prior bevacizumab treatment is required, if eligible per standard of care
5. Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
6. 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. Subjects with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, low-grade, borderline, or other ovarian tumors
3. 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.
4. Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, PKMYT1 inhibitor, or CHK1/2 inhibitor.
5. 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.
6. Unresolved toxicity of Grade \>1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).
7. Pregnant or lactating female subject or female subject of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.
8. 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.
9. Subjects who are known to be immunocompromised or HIV-positive on highly active anti-retroviral therapy.
10. Subjects with known active hepatitis B or hepatitis C infection.
11. Individuals who are judged by the Investigator to be unsuitable as study subjects.
12. Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.
Primary outcome measure(s)
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.
Trial sites (92)
Facility
City
Region
Status
Site 0170-USA Mitchell Cancer Institute
Mobile
Alabama
Recruiting
Site 0143 - HonorHealth
Phoenix
Arizona
Recruiting
Site 0102 - University of Arizona Cancer Center
Tucson
Arizona
Recruiting
Site 0258 - UC San Diego Moores Cancer Center
La Jolla
California
Active Not Recruiting
Site 0287 - Ridley Tree Cancer Center
Santa Barbara
California
Active Not Recruiting
Site 0135 - Rocky Mountain Cancer Centers
Lone Tree
Colorado
Recruiting
Site 0158 - Hartford HealthCare
Hartford
Connecticut
Recruiting
Site 0239 - Florida Cancer Specialists - East
Daytona Beach
Florida
Recruiting
Site 0241 - Florida Cancer Specialist - North
Lecanto
Florida
Recruiting
Site 0173 - Mount Sinai Medical Center
Miami Beach
Florida
Recruiting
Site 0308 - Advent Health
Orlando
Florida
Recruiting
Site 0108 - Emory University Hospital
Atlanta
Georgia
Recruiting
Site 0236 - Memorial Health
Savannah
Georgia
Active Not Recruiting
Site 0324 - Illinois Cancer Specialists
Niles
Illinois
Active Not Recruiting
Site 0284 - Community Cancer Center North
Indianapolis
Indiana
Recruiting
Site 0217 - St Vincent Hospital and Health Care Centers
Indianapolis
Indiana
Recruiting
Site 0251 - Norton Cancer Institute
Louisville
Kentucky
Recruiting
Site 0146 - Maryland Oncology Hematology, PA
Rockville
Maryland
Active Not Recruiting
Site 0221 - Tufts Medical Center - PPDS
Boston
Massachusetts
Recruiting
Site 0104 - Dana Farber Cancer Institute
Boston
Massachusetts
Recruiting
Site 0307 - Lahey Hospital and Medical Center
Burlington
Massachusetts
Recruiting
Site 0263 - Baystate Medical Center
Springfield
Massachusetts
Recruiting
Site 0101 - Barbara Ann Karmanos Cancer Institute
Detroit
Michigan
Recruiting
Site 0228 - Corewell Health Medical Group West
Grand Rapids
Michigan
Recruiting
Site 0288 - Minnesota Oncology Hematology - Maplewood
Maplewood
Minnesota
Recruiting
Site 0226 - CoxHealth
Springfield
Missouri
Active Not Recruiting
Site 0317 - Nebraska Methodist Hospital
Omaha
Nebraska
Active Not Recruiting
Site 0213 - Center of Hope
Reno
Nevada
Recruiting
Site 0231 - Northwell Health Cancer Institute
Manhasset
New York
Active Not Recruiting
Site 0126 - Wilmot Cancer Center
Rochester
New York
Recruiting
Site 0259 - Duke Cancer Center
Durham
North Carolina
Recruiting
Site 0147 - Trihealth Cancer Institute - Harold and Eugen
Cincinnati
Ohio
Recruiting
Site 0243 - Mark H Zangmeister Cancer Center
Columbus
Ohio
Recruiting
Site 0214-Ohio State University Comprehensive Cancer Center
Hilliard
Ohio
Recruiting
Site 0316 - Willamette Valley Cancer Institute/Oncology Associates of Oregon
Eugene
Oregon
Recruiting
Site 0232 - University of Pennsylvania
Philadelphia
Pennsylvania
Recruiting
Site 0178 - Thomas Jefferson University
Philadelphia
Pennsylvania
Recruiting
Site 0277 - Alliance Cancer Specialist, PC
Wynnewood
Pennsylvania
Active Not Recruiting
Site 0132 - Avera Cancer Institute
Sioux Falls
South Dakota
Recruiting
Site 0103 - University of Texas MD Anderson Cancer Center
Houston
Texas
Recruiting
+ 52 more sites — see the full list on the official registry below.
More K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc trials in Australia
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.
We use cookies to analyse site traffic and improve your experience. With your consent, we may also use cookies for advertising. You can change your choice at any time.