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

Официальное название

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)

Обзор

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.

Подробное описание

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

Вмешательства

• Препарат azenosertib
  Azenosertib (ZN-c3) will be administered orally.

Первичные конечные точки

• Objective Response Rate (ORR) defined by RECIST v1.1 [Part 2] [Срок оценки: Up to approximately 12 months from the enrollment of the last subject]

Вторичные конечные точки (5)

• Duration of response (DOR) defined by RECIST v1.1 [Part 2] [Срок оценки: Up to approximately 12 months from the enrollment of the last subject]
• Progression free survival (PFS) defined by RECIST v1.1 [Part 2] [Срок оценки: Up to approximately 12 months from the enrollment of the last subject]
• Clinical Benefit Rate (CBR) defined by RECIST v1.1 [Part 2] [Срок оценки: Up to approximately 12 months from the enrollment of the last subject]
• CA-125 response by GCIG criteria [Part 2] [Срок оценки: Up to approximately 12 months from the enrollment of the last subject]
• Number of Subjects experiencing treatment emergent adverse events (TEAEs) [Part 2] [Срок оценки: Up to approximately 12 months from the enrollment of the last subject]

Критерии участия

Критерии включения

• Age ≥18 years
• High-grade serous ovarian, fallopian tube or primary peritoneal cancer
• Tumor testing (archival acceptable) confirms a positive Cyclin E1 protein status result determined by IHC using the Sponsor's investigational clinical trial assay
• Prior therapy:

• Subjects must have platinum-resistant disease
• Parts 2a and 2b: One to 3 prior lines or regimens are allowed (1 to 4 prior lines are permitted, if prior mirvetuximab)
• 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
• Prior bevacizumab treatment is required, if eligible per standard of care
• Prior PARP inhibitor treatment is required if BRCA 1/2 mutation or HRD, if eligible per standard of care
• Prior mirvetuximab treatment is required, if eligible per standard of care
• Measurable disease per RECIST Version 1.1.
• Adequate hematologic and organ function, as defined in protocol
• ECOG 0-1

Критерии исключения

• Primary platinum-refractory disease
• Subjects with endometrioid, clear cell, mucinous, or sarcomatous histology, mixed tumors containing any of the above histologies, low-grade, borderline, or other ovarian tumors
• Any of the following treatment interventions within the specified time frame prior to C1D1:

• Major surgery within 28 days
• Hospitalization within 14 days
• Any chemotherapy or targeted tumor therapy within 21 days or 5 half-lives (whichever is shorter);
• Radiation therapy within 21 days;
• Autologous or allogeneic stem cell transplant within 3 months.
• Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).
• 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.
• Prior therapy with ZN-c3 or any other WEE1 inhibitor, ATR inhibitor, PKMYT1 inhibitor, or CHK1/2 inhibitor.
• A serious illness or medical condition(s) including, but not limited to:

• Clinically or radiographically unstable brain metastases or leptomeningeal disease that requires immediate treatment. Subjects with asymptomatic brain metastases are eligible.
• Myocardial impairment resulting in heart failure (NYHA Class II-IV)
• 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
• Acute kidney injury requiring intervention or intravenous fluid in the last 14 days or presence of indwelling urinary catheter or percutaneous nephrostomy.
• 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.
• 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
• 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.
• Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia, or skin pigmentation).
• Pregnant or lactating female subject or female subject of childbearing potential who has a positive serum pregnancy test within 14 days prior to C1D1.
• 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.
• Subjects who are known to be immunocompromised or HIV-positive on highly active anti-retroviral therapy.
• Subjects with known active hepatitis B or hepatitis C infection.
• Individuals who are judged by the Investigator to be unsuitable as study subjects.
• Subjects who had prior wide-field radiotherapy affecting ≥ 20% of the bone marrow.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 45 центров

• Site 0170-USA Mitchell Cancer Institute — Mobile
• Site 0143 - HonorHealth — Phoenix
• Site 0102 - University of Arizona Cancer Center — Tucson
• Site 0258 - UC San Diego Moores Cancer Center — La Jolla
• Site 0287 - Ridley Tree Cancer Center — Santa Barbara
• Site 0135 - Rocky Mountain Cancer Centers — Lone Tree
• Site 0158 - Hartford HealthCare — Hartford
• Site 0239 - Florida Cancer Specialists - East — Daytona Beach
• … и ещё 37 центров

Франция · 13 центров

• Site 3616 - Centre Antoine Lacassagne — Nice
• Site 3611 - ICANS - Institut de cancérologie Strasbourg Europe — Strasbourg
• Site 3601 - Centre Georges François Leclerc — Dijon
• Site 3613 - CHRU Besancon - Hopital Jean Minjoz — Besançon
• Site 3617 - CHU de Brest - Hôpital La Cavale Blanche — Brest
• Site 3603 - Institut Claudius Regaud — Toulouse
• Site 3602 - Centre Oscar Lambret — Lille
• Site 3615 - Hôpital Cochin Port-Royal AP-HP — Paris
• … и ещё 5 центров

Италия · 8 центров

• Site 3302 - Istituto Nazionale Tumori IRCCS Fondazione Giovanni Pascale — Naples
• Site 3308 - Azienda Ospedaliero Universitaria Di Modena Policlinico — Modena
• Site 3312 - Centro di Riferimento Oncologico — Aviano
• Site 3304 - Fondazione Policlinico Universitario A Gemelli — Rome
• Site 3305 - Istituto Europeo di Oncologia — Milan
• Site 3307 - Ospedale San Raffaele S.r.l. — Milan
• Site 3311 - Azienda Ospedaliera Universitaria Integrata Di Verona — Verona
• Site 3303 - Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi-V — Bologna

Австралия · 7 центров

• Site 2715 - Icon Cancer Centre - Chermside — Chermside
• Site 2707 - Mater Brisbane — South Brisbane
• Site 2709 - Cancer Research SA — Adelaide
• Site 2702 - Burnside War Memorial Hospital - The Brian Fricker Oncology Centre — Toorak Gardens
• Site 2716 - Epworth Healthcare Freemasons — East Melbourne
• Site 2701 - Sir Charles Gairdner Hospital — Nedlands
• Site 2717 - St John of God Hospital Subiaco — Subiaco

South Korea · 6 центров

Список центров уточняется — проверьте первичный протокол.

Польша · 5 центров

• Site 2414 - Med-Polonia Sp. z o.o. — Poznan
• Site 2405 - Centrum Badan Klinicznych JCI — Krakow
• Site 2404 - Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut — Warsaw
• Site 2419 - Bialostockie Centrum Onkologii im. Marii Sklodowskiej-Curie w Bialymstoku — Bialystok
• … и ещё 1 центр

Испания · 5 центров

Список центров уточняется — проверьте первичный протокол.

Бельгия · 3 центра

• Site 3102 - Cliniques Universitaires Saint-Luc — Brussels
• Site 3101 - AZORG - Aalst — Aalst
• Site 3105 - UZ Leuven — Leuven

Идентификаторы

NCT: NCT05128825 · ZN-c3-005

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗