Clinical trial NCT05128825: A Study of Azenosertib (ZN-c3) in Subjects With Platinum-Resistant High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: High-Grade Serous Ovarian, Fallopian Tube or Primary Peritoneal Cancer
Keywords: Cyclin E1, CCNE1, Ovarian Cancer, Platinum Resistant, WEE1 inhibitor, DENALI, GOG-3066
Lead sponsor: K-Group, Beta, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc
Sponsor class: INDUSTRY
First posted: 2021-11-22
Enrollment: 170
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1a/1b (Arm completed enrollment); Part 2a-Arm 1 (Enrolling); Part 2a-Arm 2 (Enrolling); Part 2b (Arm not yet recruiting)
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2]
timeFrame: Up to approximately 12 months from the enrollment of the last subject
Secondary outcomes:
measure: Duration of response (DOR) defined by RECIST v1.1 [Part 2]
timeFrame: Up to approximately 12 months from the enrollment of the last subject
measure: Progression free survival (PFS) defined by RECIST v1.1 [Part 2]
timeFrame: Up to approximately 12 months from the enrollment of the last subject
measure: Clinical Benefit Rate (CBR) defined by RECIST v1.1 [Part 2]
timeFrame: Up to approximately 12 months from the enrollment of the last subject
measure: CA-125 response by GCIG criteria [Part 2]
timeFrame: Up to approximately 12 months from the enrollment of the last subject
measure: Number of Subjects experiencing treatment emergent adverse events (TEAEs) [Part 2]
timeFrame: Up to approximately 12 months from the enrollment of the last subject
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Site 0170-USA Mitchell Cancer Institute
state: Alabama
city: Phoenix
country: United States
facility: Site 0143 - HonorHealth
state: Arizona
city: La Jolla
country: United States
facility: Site 0258 - UC San Diego Moores Cancer Center
state: California
city: Santa Barbara
country: United States
facility: Site 0287 - Ridley Tree Cancer Center
state: California
city: Lone Tree
country: United States
facility: Site 0135 - Rocky Mountain Cancer Centers
state: Colorado
city: Daytona Beach
country: United States
facility: Site 0239 - Florida Cancer Specialists - East
state: Florida
city: Miami Beach
country: United States
facility: Site 0173 - Mount Sinai Medical Center
state: Florida
city: Savannah
country: United States
facility: Site 0236 - Memorial Health
state: Georgia
city: Indianapolis
country: United States
facility: Site 0284 - Community Health Network
state: Indiana
city: Louisville
country: United States
facility: Site 0251 - Norton Cancer Institute
state: Kentucky
city: Rockville
country: United States
facility: Site 0146 - Maryland Oncology Hematology, PA
state: Maryland
city: Boston
country: United States
facility: Site 0221 - Tufts Medical Center - PPDS
state: Massachusetts
city: Burlington
country: United States
facility: Site 0307 - Lahey Hospital and Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Site 0263 - Baystate Medical Center
state: Massachusetts
city: Grand Rapids
country: United States
facility: Site 0228 - Corewell Health Medical Group West
state: Michigan
city: Maplewood
country: United States
facility: Site 0288 - Minnesota Oncology Hematology - Maplewood
state: Minnesota
city: Springfield
country: United States
facility: Site 0226 - CoxHealth
state: Missouri
city: Omaha
country: United States
facility: Site 0317 - Nebraska Methodist Hospital
state: Nebraska
city: Reno
country: United States
facility: Site 0213 - Center of Hope
state: Nevada
city: Manhasset
country: United States
facility: Site 0231 - Northwell Health Cancer Institute
state: New York
city: Durham
country: United States
facility: Site 0259 - Duke Cancer Center
state: North Carolina
city: Cincinnati
country: United States
facility: Site 0147 - Trihealth Cancer Institute - Harold and Eugen
state: Ohio
city: Columbus
country: United States
facility: Site 0243 - Mark H Zangmeister Cancer Center
state: Ohio
city: Hilliard
country: United States
facility: Site 0214-Ohio State University Comprehensive Cancer Center
state: Ohio
city: Eugene
country: United States
facility: Site 0316 - Oncology Associates of Oregon, P.C.
state: Oregon
city: Philadelphia
country: United States
facility: Site 0232 - University of Pennsylvania
state: Pennsylvania
city: Wynnewood
country: United States
facility: Site 0277 - Alliance Cancer Specialist, PC
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Site 0132 - Avera Cancer Institute
state: South Dakota
city: Tyler
country: United States
facility: Site 0203 - Texas Oncology
state: Texas
city: Chesapeake
country: United States
facility: Site 0295 - Virginia Oncology Associates
state: Virginia
city: Brisbane
country: Australia
facility: Site 2715 - Icon Cancer Centre - Chermside
state: Queensland
city: South Brisbane
country: Australia
facility: Site 2707 - Mater Brisbane
state: Queensland
city: Adelaide
country: Australia
facility: Site 2709 - Icon Cancer Research Adelaide
state: South Australia
city: Toorak Gardens
country: Australia
facility: Site 2702 - Burnside War Memorial Hospital - The Brian Fricker Oncology Centre
state: South Australia
city: Nedlands
country: Australia
facility: Site 2701 - Sir Charles Gairdner Hospital
state: Western Australia
city: Subiaco
country: Australia
facility: Site 2717 - St John of God Hospital Subiaco
state: Western Australia
city: Nice
country: France
facility: Site 3616 - Centre Antoine Lacassagne
state: Alpes-Maritimes
city: Lille
country: France
facility: Site 3602 - Centre Oscar Lambret
state: Nord
city: Saint-Herblain
country: France
facility: Site 3614 - Institut de Cancerologie de l'oust
state: Pays de la Loire
city: Pierre-Bénite
country: France
facility: Site 3608 - Hospices Civils de Lyon - Hôpital Lyon Sud
state: Rhône
city: Villejuif
country: France
facility: Site 3604 - Institut Gustave Roussy
city: Krakow
country: Poland
facility: Site 2405 - Centrum Badan Klinicznych JCI
state: Malopolskie
Study officials:
References: