Clinical trial • Phase II • Oncology
AZENOSERTIB for High-grade serous ovarian cancer | Fallopian tube cancer | Primary peritoneal carcinoma
Phase II trial of AZENOSERTIB for High-grade serous ovarian cancer | Fallopian tube cancer | Primary peritoneal carcinoma.
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- High-grade serous ovarian cancer | Fallopian tube cancer | Primary peritoneal carcinoma
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 29-09-2023
- First CTIS Authorization Date
- 02-02-2024
Trial design
Randomised, open-label, azenosertib (zn-c3) 300 mg 5:2 dosing regimen versus azenosertib (zn-c3) 400 mg 5:2 dosing regimen-controlled Phase II trial across 36 sites in Belgium, Italy, Poland and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Azenosertib (ZN-c3) 300 mg 5:2 dosing regimen versus Azenosertib (ZN-c3) 400 mg 5:2 dosing regimen
- Biomarker Stratified
- True, biomarker: cyclin E1 (CCNE1); strata: centrally determined cyclin E1-positive subjects with subgroups with and without detectable CCNE1 gene amplification
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 116
Eligibility
Recruits 116 The trial record indicates isVulnerablePopulationSelected = true. Participation requires "Provision of signed ICF" and inclusion criterion specifies females aged ≥18 years (or local age of majority). Informed consent must be provided by the participant (signed ICF). Age-specific assent is not applicable because only adult participants (≥18 or local age of majority) are eligible. Country-specific ICFs and related consent documents are provided (see ICF documents per country)..
- Vulnerable Population
- The trial record indicates isVulnerablePopulationSelected = true. Participation requires "Provision of signed ICF" and inclusion criterion specifies females aged ≥18 years (or local age of majority). Informed consent must be provided by the participant (signed ICF). Age-specific assent is not applicable because only adult participants (≥18 or local age of majority) are eligible. Country-specific ICFs and related consent documents are provided (see ICF documents per country).
Inclusion criteria
- {"criterion_text":"- 1. Provision of signed ICF\n- 2. Female Age ≥18 years (or age of majority in local region) at the time of informed consent.\n- 3. Histologically or cytologically confirmed recurrent, high-grade serous ovarian, fallopian tube, or primary peritoneal cancer\n- 4. Subject must have platinum-resistant disease\n- 5. Subjects must have received 1-3 prior lines of therapy (up to 4 if prior mirvetuximab) for Part 2 (up to 4 if prior mirvetuximab)\n- 6. Prior mirvetuximab is required if approved and available for eligible subjects\n- 7. Subjects must have at least one measurable lesion as defined by RECIST Guideline Version 1.1\n- 8. Performance Status: Eastern Cooperative Oncology Group (ECOG) score of ≤1.\n- 9. Adequate hematologic and organ function during the Screening Period For the complete Inclusion Criteria, please refer to the study protocol"}
Exclusion criteria
- {"criterion_text":"- 1. Platinum refractory disease (in front line therapy)\n- 2. Any of the following treatment interventions within the specified time frame prior to Cycle 1 Day 1 (C1D1): a. Hospitalization for any reason within 14 days c. Any chemotherapy or targeted tumor therapy within 14 days or 5 half-lives (whichever is shorter); d. Radiation therapy within 21 days; however, if the radiation portal covered ≤5% of the bone marrow, the subject is eligible irrespective of the end date of radiotherapy. e. Autologous or allogeneic stem cell transplant within 3 months. f. Current use of any other investigational drug therapy <28 days or 5 half-lives (whichever is shorter).\n- 3. Prior therapy with azenosertib or any other WEE1 inhibitor, ATR inhibitor, CHK1/2 inhibitor, or PKMYT1 inhibitor.\n- 4. A serious illness or medical conditions, listed in study protocol, including:\n- 6. Unresolved toxicity of Grade >1 attributed to any prior therapies (excluding Grade ≤2 neuropathy, alopecia or skin pigmentation). For the complete Exclusion Criteria, please refer to the study protocol"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Part 1b: •\tFrequency and severity of TEAEs • Incidence of dose interruptions, dose reductions, and permanent discontinuations of ZN-c3 azenosertib due to related TEAEs\n- Part 2a: Independent primary endpoints: ORR as defined by RECIST v1.1 and as assessed by the Investigator in subjects with centrally determined cyclin E1-positive status • Frequency and severity of TEAEs\n- Part 2b: • ORR as defined by RECIST v1.1 and as assessed by ICR in subjects with centrally determined cyclin E1-positive status","definition_or_measurement_approach":"Part 1b: Safety endpoints measured as frequency and severity of treatment-emergent adverse events (TEAEs) and incidence of dose interruptions/reductions/permanent discontinuations attributed to ZN-c3. Part 2a: ORR defined by RECIST v1.1 assessed by the Investigator in centrally determined cyclin E1-positive subjects; safety measured as frequency and severity of TEAEs. Part 2b: ORR defined by RECIST v1.1 assessed by independent central review (ICR) in centrally determined cyclin E1-positive subjects."}
Secondary endpoints
- {"endpoint_text":"- Part 1b: • Summarized by cohort and overall: o ORR, DOR, TTR, PFS, and CBR as defined by RECIST v1.1 and as assessed by ICR and the Investigator o OS o CA-125 response by GCIG criteria • Plasma concentrations of azenosertib\n- Part 2a: • DOR, TTR, PFS, and CBR as defined by RECIST v1.1 and as assessed by the Investigator • OS • CA-125 response by GCIG criteria • ORR and DOR as defined by RECIST v1.1 and as assessed by the Investigator • Systemic plasma concentrations of azenosertib\n- Part 2b: • Frequency and severity of TEAEs • ORR, DOR, TTR, PFS, and CBR as defined by RECIST v1.1 as assessed by the Investigator • DOR, TTR, PFS, and CBR as defined by RECIST v1.1 as assessed by ICR • OS • CA-125 response by GCIG criteria • ORR and DOR as defined by RECIST v1.1 as assessed by the Investigator","definition_or_measurement_approach":"Tumor efficacy endpoints (ORR, DOR, TTR, PFS, CBR) are defined by RECIST v1.1 and assessed by Investigator and/or ICR as specified; OS measured as overall survival; CA-125 response assessed by GCIG criteria; plasma/systemic concentrations of azenosertib measured for PK analysis; safety endpoints measured as frequency and severity of TEAEs."}
Recruitment
- Planned Sample Size
- 116
- Recruitment Window Months
- 43
- Consent Approach
- Informed consent required: "Provision of signed ICF" (principal inclusion criterion). Participants must provide signed ICF; participants are female adults (≥18 years or local age of majority). Country-specific informed consent documents are provided (main ICFs, prescreening ICFs, pregnancy and partner ICFs) in multiple languages (examples in the record: English, French, Dutch, Italian, Polish, Spanish). Assent procedures are not applicable because only adult participants are eligible.
Geography
- Total Number Of Sites
- 36
- Total Number Of Participants
- 137
Belgium
- Earliest CTIS Part Ii Submission Date
- 08-01-2024
- Latest Decision Or Authorization Date
- 15-12-2025
- Processing Time Days
- 707
- Number Of Sites
- 4
- Number Of Participants
- 27
Sites
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Medical Oncology
- Contact Person Name
- Jean-François Baurain
- Contact Person Email
- jf.baurain@uclouvain.be
- Site Name
- Onze-Lieve-Vrouwziekenhuis
- Department Name
- Medical Oncology
- Contact Person Name
- Greet Huygh
- Contact Person Email
- Greet.huygh@olvz-aalst.be
- Site Name
- UZ Leuven
- Department Name
- Gynecologic Oncology
- Contact Person Name
- Toon Van Gorp
- Contact Person Email
- toon.vangorp@uzleuven.be
- Site Name
- Centre Hospitalier Universitaire Dinant Godinne Sainte-Elisabeth-UCL-Namur
- Department Name
- Oncology
- Contact Person Name
- Stéphanie Henry
- Contact Person Email
- stephanie.henry@chuuclnamur.uclouvain.be
Italy
- Earliest CTIS Part Ii Submission Date
- 17-01-2024
- Latest Decision Or Authorization Date
- 16-12-2025
- Processing Time Days
- 699
- Number Of Sites
- 8
- Number Of Participants
- 50
Sites
- Site Name
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS
- Department Name
- Ginecologia Oncologica
- Contact Person Name
- Anna Fagotti
- Contact Person Email
- anna.fagotti@policlinicogemelli.it
- Site Name
- Azienda Ospedaliero Universitaria Di Modena
- Department Name
- Oncologia ed Ematologia
- Contact Person Name
- Roberto Sabbatini
- Contact Person Email
- roberto.sabbatini@unimore.it
- Site Name
- European Institute Of Oncology S.r.l.
- Department Name
- Ginecologia Oncologica Medica
- Contact Person Name
- Nicoletta Colombo
- Contact Person Email
- nicoletta.colombo@ieo.it
- Site Name
- IRCCS Istituto Nazionale Tumori Fondazione Pascale
- Department Name
- S.C. Oncologia Clinica Sperimentale Uro-Ginecologica
- Contact Person Name
- Sabrina Chiara Cecere
- Contact Person Email
- s.cecere@istitutotumori.na.it
- Site Name
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
- Department Name
- Oncologia Medica
- Contact Person Name
- Claudio Zamagni
- Contact Person Email
- claudio.zamagni@aosp.bo.it
- Site Name
- Ospedale San Raffaele S.r.l.
- Department Name
- Ostetricia e Ginecologia
- Contact Person Name
- Alice Bergamini
- Contact Person Email
- bergamini.alice@hsr.it
- Site Name
- Centro Di Riferimento Oncologico Di Aviano
- Department Name
- Oncologia Medica e Prevenzione Oncologica
- Contact Person Name
- Michele Bartoletti
- Contact Person Email
- michele.bartoletti@cro.it
- Site Name
- Centro Ricerche Cliniche Di Verona S.r.l.
- Department Name
- Centro Ricerche Cliniche
- Contact Person Name
- Andrea Zivi
- Contact Person Email
- andrea.zivi@aovr.veneto.it
Poland
- Earliest CTIS Part Ii Submission Date
- 22-01-2024
- Latest Decision Or Authorization Date
- 16-12-2025
- Processing Time Days
- 694
- Number Of Sites
- 5
- Number Of Participants
- 20
Sites
- Site Name
- Bialostockie Centrum Onkologii Im. Marii Sklodowskiej-Curie W Bialymstoku
- Department Name
- Oddział Onkologii Ginekologicznej
- Contact Person Name
- Beata Maćkowiak-Matejczyk
- Contact Person Email
- bmackowiak@onkologia.bialystok.pl
- Site Name
- Szpitale Pomorskie Sp. z o.o.
- Department Name
- Oddział Onkologii i Radioterapii, Onkologia Kliniczna – „Leczenie jednego dnia”
- Contact Person Name
- Joanna Pikiel
- Contact Person Email
- joanna.pikiel@post.pl
- Site Name
- Med Polonia Sp. z o.o.
- Department Name
- Med Polonia Sp. z o.o.
- Contact Person Name
- Rodryg Ramlau
- Contact Person Email
- rramlau@gmail.com
- Site Name
- Jagiellońskie Centrum Innowacji Sp. z o.o.
- Department Name
- Centrum Badań Klinicznych
- Contact Person Name
- Paweł Blecharz
- Contact Person Email
- pawel.blecharz@interia.pl
- Site Name
- Narodowy Instytut Onkologii Im. Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
- Department Name
- Oddział Badań Wczesnych Faz
- Contact Person Name
- Iwona Ługowska
- Contact Person Email
- iwona.lugowska@nio.gov.pl
Spain
- Earliest CTIS Part Ii Submission Date
- 27-10-2023
- Latest Decision Or Authorization Date
- 18-12-2025
- Processing Time Days
- 783
- Number Of Sites
- 6
- Number Of Participants
- 20
Sites
- Site Name
- Hospital Universitario La Paz
- Department Name
- Oncology
- Contact Person Name
- Andres Redondo Sanchez
- Contact Person Email
- aredondo12@gmail.com
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Oncology
- Contact Person Name
- Ana Oaknin Benzaquen
- Contact Person Email
- aoaknin@vhio.net
- Site Name
- University Clinical Hospital Virgen De La Arrixaca
- Department Name
- Oncologia
- Contact Person Name
- Jeronimo Martinez Garcia
- Contact Person Email
- jeronimo@seom.org
- Site Name
- Clinica Universidad De Navarra (Madrid)
- Department Name
- Oncology
- Contact Person Name
- Antonio Gonzalez Martin
- Contact Person Email
- agonzalezma@unav.es
- Site Name
- Clinica Universidad De Navarra (Pamplona)
- Department Name
- Oncology
- Contact Person Name
- Antonio Gonzalez Martin
- Contact Person Email
- agonzalezma@unav.es
- Site Name
- Hospital Clinico Universitario De Valencia
- Department Name
- Oncology
- Contact Person Name
- Jose Alejandro Perez Fidalgo
- Contact Person Email
- japfidalgo@msn.com
France
- Earliest CTIS Part Ii Submission Date
- 01-12-2023
- Latest Decision Or Authorization Date
- 22-01-2026
- Processing Time Days
- 782
- Number Of Sites
- 13
- Number Of Participants
- 20
Sites
- Site Name
- Institut De Cancerologie De L Ouest
- Department Name
- Oncologie Médicale
- Contact Person Name
- Jean-Sébastien Frenel
- Contact Person Email
- jean-sebastien.frenel@ico.unicancer.fr
- Site Name
- Institut Gustave Roussy
- Department Name
- Médecine Oncologique
- Contact Person Name
- Alexandra Leary
- Contact Person Email
- alexandra.leary@gustaveroussy.fr
- Site Name
- Besancon University Hospital Center
- Department Name
- Oncologie Médicale
- Contact Person Name
- Laura Mansi
- Contact Person Email
- lmansi@chu-besancon.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Oncologie Médicale
- Contact Person Name
- Jérôme Alexandre
- Contact Person Email
- jerome.alexandre@aphp.fr
- Site Name
- Institut Universitaire Du Cancer Toulouse-Oncopole
- Department Name
- Oncologie Médicale
- Contact Person Name
- Laurence Gladieff
- Contact Person Email
- gladieff.laurence@iuct-oncopole.fr
- Site Name
- Centre Leon Berard
- Department Name
- Oncologie Médicale
- Contact Person Name
- Olivia LE SAUX
- Contact Person Email
- olivia.lesaux@lyon.unicancer.fr
- Site Name
- Centre Antoine Lacassagne
- Contact Person Name
- Philippe Follana
- Contact Person Email
- philippe.follana@nice.unicancer.fr
- Site Name
- Institut De Cancerologie Strasbourg Europe
- Department Name
- Oncologie Médicale
- Contact Person Name
- Lauriane Eberst
- Contact Person Email
- l.eberst@icans.eu
- Site Name
- Centr Georges Francois Leclerc
- Department Name
- Oncologie Médicale
- Contact Person Name
- Jean-David Fumet
- Contact Person Email
- jdfumet@cgfl.fr
- Site Name
- Les Hopitaux Universitaires De Strasbourg
- Department Name
- Oncologie Médicale
- Contact Person Name
- Lauriane EBERST
- Contact Person Email
- l.eberst@icans.eu
- Site Name
- Centre Oscar Lambret
- Department Name
- Oncologie Médicale
- Contact Person Name
- Cyril Abdeddaim
- Contact Person Email
- c-abdeddaim@o-lambret.fr
- Site Name
- Centre Hospitalier Regional Et Universitaire De Brest
- Department Name
- Institut de Cancérologie et d’Imagerie
- Contact Person Name
- Laura Deiana
- Contact Person Email
- laura.deiana@chu-brest.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Oncologie Médicale
- Contact Person Name
- Benoit You
- Contact Person Email
- benoit.you@chu-lyon.fr
Sponsor
Primary sponsor
- Full Name
- K-Group Beta Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- PPD International Holdings LLC
- Responsibilities
- lab kit build, Biological sample management
- Name
- PPD Development LP
- Name
- Everest Clinical Research Corporation
Third parties
- {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"lab kit build, Biological sample management","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Central imaging","organisation_type":"Laboratory/Research/Testing facility"}
- {"country":"Germany","full_name":"Discovery Life Sciences Biomarker Services GmbH","duties_or_roles":"IHC Testing","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
- {"country":"Germany","full_name":"PCI Pharma Services Germany GmbH","duties_or_roles":"Clinical Supply","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"NGS testing","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"Plasma cfDNA sample analysis","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"samples storage","organisation_type":"Pharmaceutical company"}
- {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- Azenosertib (also known as ZN-c3; KP-2638)
- Active Substance
- AZENOSERTIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Starting Dose
- 300 mg (5:2)
- Dose Levels
- 300 mg 5:2 | 400 mg 5:2
- Frequency
- 5 days on, 2 days off (5:2) per cycle
- Maximum Dose
- 400 mg (max daily dose amount 400 mg)
- Dose Escalation Increase
- 300 mg -> 400 mg
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