RECRUITING

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

Conditions

High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer Cyclin E1, CCNE1, Ovarian Cancer, Platinum Resistant, WEE1 inhibitor, DENALI, GOG-3066

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

A Phase 2 Open-Label, Multicenter Study To Evaluate Efficacy And Safety Of ZN-c3 In Subjects With High-Grade Serous Ovarian, Fallopian Tube, Or Primary Peritoneal Cancer (DENALI / ZN-c3-005 / GOG-3066)

Quick Facts

Study Start:2022-02-17

Study Completion:2027-06-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05128825

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:FEMALE

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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	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.

Inclusion Criteria

Exclusion 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

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.

Contacts and Locations

Study Contact

Project Director

CONTACT

858.263.4333

medicalaffairs@zentalis.com

Study Locations (Sites)

Site 0170-USA Mitchell Cancer Institute

Mobile, Alabama, 36604

United States

Site 0143 - HonorHealth

Phoenix, Arizona, 85016

United States

Site 0258 - UC San Diego Moores Cancer Center

La Jolla, California, 92037

United States

Site 0287 - Ridley Tree Cancer Center

Santa Barbara, California, 93105

United States

Site 0135 - Rocky Mountain Cancer Centers

Lone Tree, Colorado, 80218

United States

Site 0239 - Florida Cancer Specialists - East

Daytona Beach, Florida, 32117

United States

Site 0173 - Mount Sinai Medical Center

Miami Beach, Florida, 33140

United States

Site 0236 - Memorial Health

Savannah, Georgia, 31404

United States

Site 0284 - Community Health Network

Indianapolis, Indiana, 46250

United States

Site 0251 - Norton Cancer Institute

Louisville, Kentucky, 40202

United States

Site 0146 - Maryland Oncology Hematology, PA

Rockville, Maryland, 20876

United States

Site 0221 - Tufts Medical Center - PPDS

Boston, Massachusetts, 02111

United States

Site 0307 - Lahey Hospital and Medical Center

Burlington, Massachusetts, 01805

United States

Site 0263 - Baystate Medical Center

Springfield, Massachusetts, 01199

United States

Site 0288 - Minnesota Oncology Hematology - Maplewood

Maplewood, Minnesota, 55109

United States

Site 0226 - CoxHealth

Springfield, Missouri, 65807

United States

Site 0317 - Nebraska Methodist Hospital

Omaha, Nebraska, 68114

United States

Site 0213 - Center of Hope

Reno, Nevada, 89511

United States

Site 0231 - Northwell Health Cancer Institute

Manhasset, New York, 11030

United States

Site 0259 - Duke Cancer Center

Durham, North Carolina, 27710

United States

Site 0147 - Trihealth Cancer Institute - Harold and Eugen

Cincinnati, Ohio, 45242

United States

Site 0243 - Mark H Zangmeister Cancer Center

Columbus, Ohio, 43219

United States

Site 0214-Ohio State University Comprehensive Cancer Center

Hilliard, Ohio, 43026

United States

Site 0316 - Oncology Associates of Oregon, P.C.

Eugene, Oregon, 97401

United States

Site 0232 - University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

Site 0277 - Alliance Cancer Specialist, PC

Wynnewood, Pennsylvania, 19096

United States

Site 0132 - Avera Cancer Institute

Sioux Falls, South Dakota, 57105

United States

Site 0203 - Texas Oncology

Tyler, Texas, 75702

United States

Site 0295 - Virginia Oncology Associates

Chesapeake, Virginia, 23320

United States

Collaborators and Investigators

Sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-02-17

Study Completion Date2027-06-30

Study Record Updates

Study Start Date2022-02-17

Study Completion Date2027-06-30

Terms related to this study

Keywords Provided by Researchers

Cyclin E1, CCNE1, Ovarian Cancer, Platinum Resistant, WEE1 inhibitor, DENALI, GOG-3066

Additional Relevant MeSH Terms

High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer