Clinical trial • Phase III • Oncology
VORASIDENIB for IDH-mutant astrocytoma (WHO grade 2 or 3)
Phase III trial of VORASIDENIB for IDH-mutant astrocytoma (WHO grade 2 or 3).
Overview
- Trial Therapeutic Area
- Oncology
- Trial Disease
- IDH-mutant astrocytoma (WHO grade 2 or 3)
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 10-07-2025
- First CTIS Authorization Date
- 04-11-2025
Trial design
Randomised, vorasidenib (s95032/ag-881) oral film-coated tablet (formulations referenced as 10 mg and 40 mg) versus matching placebo tablets supplied as film-coated oral tablets.-controlled Phase III trial across 27 sites in France, Spain, Netherlands and others.
- Randomised
- Yes
- Comparator
- Vorasidenib (S95032/AG-881) oral film-coated tablet (formulations referenced as 10 mg and 40 mg) versus matching placebo tablets supplied as film-coated oral tablets.
- Target Sample Size
- 221
Eligibility
Recruits 221 Vulnerable population flag selected in record. Informed consent is required (Inclusion criterion 1: "Informed consent"). Participants must be adults (Age ≥ 18 years). Subject information and informed consent forms (L1_SIS and ICF) and patient-facing documents are provided in multiple languages; no pediatric assent procedures are described..
- Pregnancy Exclusion
- 11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within two weeks prior to enrolment; a serum or urine pregnancy test must be conducted and confirmed negative within 72 hours prior to the first dose of study treatment.
- Vulnerable Population
- Vulnerable population flag selected in record. Informed consent is required (Inclusion criterion 1: "Informed consent"). Participants must be adults (Age ≥ 18 years). Subject information and informed consent forms (L1_SIS and ICF) and patient-facing documents are provided in multiple languages; no pediatric assent procedures are described.
Inclusion criteria
- {"criterion_text":"- 1. Informed consent\n- 10. Stable or decreasing corticosteroid dose, or no use of corticoids, for at least 7 days prior to enrolment.\n- 11. Women of childbearing potential (WOCBP) must have a negative serum pregnancy test within two weeks prior to enrolment; a serum or urine pregnancy test must be conducted and confirmed negative within 72 hours prior to the first dose of study treatment.\n- 12. Participants of childbearing / reproductive potential should use two adequate methods of birth control, including a highly effective method and a barrier method during the study treatment period and for at least 90 days after the last dose of treatment.\n- 2. Age ≥ 18 years\n- 3. Integrated diagnosis of astrocytoma, IDH-mutant, CNS5 WHO grade 2 or 3, per local assessment, with documented IDH1 or IDH2 mutation based on local testing of tumour tissue.\n- 4. At least 1 prior surgery for glioma.\n- 5. Completed first-line standard of care radiotherapy (minimum 50.4 Gy, photons or protons allowed) followed by SoC adjuvant chemotherapy (i.e., either 4-12 cycles of temozolomide or 2-6 cycles of PCV).\n- 6. Last chemotherapy dose of first line chemoradiotherapy more than 6 weeks and less than 12 weeks before enrolment.\n- 7. Recovered from any clinically relevant toxicity of the previous chemoradiotherapy unless stable and manageable per investigator´s judgement\n- 8. Adequate bone marrow, renal, and hepatic function, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at or below ULN.\n- 9. WHO performance status 0-2"}
Exclusion criteria
- {"criterion_text":"- 1. Presence of 1p19q co-deletion, per local assessment.\n- 2. Tumour recurrence or progression per RANO 2.0 criteria between first day of radiotherapy and enrolment, per local assessment\n- 3. Any prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen.\n- 4. Integrated diagnosis of astrocytoma, IDH-mutated, CNS5 WHO grade 4\n- 5. Ongoing use of medications that are CYP2C8, CYP2C9, CYP2C19, or CYP3A substrates with a narrow therapeutic index. Participants must be transferred to other medications before receiving the first dose of study drug"}
Endpoints
Primary endpoints
- {"endpoint_text":"- The primary endpoint is PFS, as assessed locally from the date of enrolment using the RANO 2.0 criteria.","definition_or_measurement_approach":"Progression-free survival (PFS) assessed locally from date of enrolment using RANO 2.0 criteria."}
Secondary endpoints
- {"endpoint_text":"- PFS by retrospective central radiological assessment from the date of enrolment using the RANO 2.0 criteria.","definition_or_measurement_approach":"Retrospective central radiological assessment of PFS from enrolment using RANO 2.0 criteria."}
- {"endpoint_text":"- PFS from the start of radiotherapy (both local and retrospective central radiological assessment) using RANO 2.0 criteria.","definition_or_measurement_approach":"PFS measured from start of radiotherapy, assessed both locally and by retrospective central radiological review using RANO 2.0 criteria."}
- {"endpoint_text":"- OS from date of enrolment.","definition_or_measurement_approach":"Overall survival measured from date of enrolment."}
- {"endpoint_text":"- Best response, overall response, disease control and complete response rate (both local and retrospective central radiological assessment) as well as duration of response using RANO 2.0 criteria.","definition_or_measurement_approach":"Radiological response assessments (local and retrospective central) using RANO 2.0 criteria; includes best response, overall response, disease control, complete response rate, and duration of response."}
- {"endpoint_text":"- TTNI","definition_or_measurement_approach":"Time to next intervention (TTNI)."}
- {"endpoint_text":"- Safety according to the CTCAE (NCI Common Terminology Criteria for Adverse Events) Version 5.0.","definition_or_measurement_approach":"Adverse events graded per CTCAE v5.0."}
- {"endpoint_text":"- HRQoL will be assessed","definition_or_measurement_approach":"Health-related quality of life assessments (instruments referenced in patient-facing documents)."}
- {"endpoint_text":"- Neurological symptoms and signs, assessed using the NANO scale and measured by neurological progression-free survival (NPFS) and Seizure Control Composite Score Index.","definition_or_measurement_approach":"Neurological assessment using the NANO scale; NPFS and Seizure Control Composite Score Index used as measures."}
- {"endpoint_text":"- Neurocognitive function, as assessed by a test battery consisting of HVLT-R, TMT, COWA test, and MOS scale","definition_or_measurement_approach":"Neurocognitive battery including HVLT-R, Trail Making Test (TMT), COWA, and MOS scale."}
Recruitment
- Planned Sample Size
- 221
- Recruitment Window Months
- 128
- Consent Approach
- Informed consent required from each participant (Inclusion criterion 1). Participants are adults (≥18) and provide consent themselves. Subject information and informed consent forms (L1_SIS and ICF) and patient-facing documents are available for publication and in multiple language versions (files include language variants such as DE, FR, ES, IT, NL, CS and an English lay synopsis), and specific ICFs addressing pregnancy and pregnant partner are provided. Women of childbearing potential must have negative pregnancy testing and adhere to contraception requirements per protocol.
Geography
- Total Number Of Sites
- 27
- Total Number Of Participants
- 247
France
- Earliest CTIS Part Ii Submission Date
- 03-10-2025
- Latest Decision Or Authorization Date
- 06-11-2025
- Processing Time Days
- 34
- Number Of Sites
- 5
- Number Of Participants
- 51
Sites
- Site Name
- Hospices Civils De Lyon
- Department Name
- Neuro-oncologie
- Contact Person Name
- Francois Ducray
- Contact Person Email
- francois.ducray@chu-lyon.fr
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Neuro-oncology
- Contact Person Name
- Alice Laurenge-Leprince
- Contact Person Email
- alice.laurenge@aphp.fr
- Site Name
- Centre Hospitalier Universitaire De Bordeaux
- Department Name
- Oncology Dept
- Contact Person Name
- Charlotte Bronnimann
- Contact Person Email
- charlotte.bronnimann@chu-bordeaux.fr
- Site Name
- Oncopole Claudius Regaud
- Department Name
- Radiation Oncology
- Contact Person Name
- Elizabeth Cohen-Jonathan Moyal
- Contact Person Email
- moyal.elizabeth@iuct-oncopole.fr
- Site Name
- Centre Hospitalier Regional De Marseille
- Department Name
- Neurooncology
- Contact Person Name
- Emeline Tabouret
- Contact Person Email
- emeline.tabouret@ap-hm.fr
Spain
- Earliest CTIS Part Ii Submission Date
- 03-10-2025
- Latest Decision Or Authorization Date
- 05-11-2025
- Processing Time Days
- 33
- Number Of Sites
- 3
- Number Of Participants
- 20
Sites
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Medical Oncology
- Contact Person Name
- Maria Vieito Villar
- Contact Person Email
- mvieito@vhio.net
- Site Name
- Hospital De La Santa Creu I Sant Pau
- Department Name
- Dept of Oncology
- Contact Person Name
- Oscar Gallego Rubio
- Contact Person Email
- ogallego@santpau.cat
- Site Name
- Hospital Universitario 12 De Octubre
- Department Name
- Medical Oncology Department / Neurooncology Unit
- Contact Person Name
- Juan Manuel Sepulveda
- Contact Person Email
- sepulvedasanchez@seom.org
Netherlands
- Earliest CTIS Part Ii Submission Date
- 03-10-2025
- Latest Decision Or Authorization Date
- 06-11-2025
- Processing Time Days
- 34
- Number Of Sites
- 3
- Number Of Participants
- 36
Sites
- Site Name
- Amsterdam UMC Stichting
- Department Name
- Department of Medical Oncology
- Contact Person Name
- Myra van Linde
- Contact Person Email
- m.vanlinde@amsterdamumc.nl
- Site Name
- Academisch Ziekenhuis Maastricht
- Department Name
- Department of Medical Oncology
- Contact Person Name
- Ann Hoeben
- Contact Person Email
- ann.hoeben@mumc.nl
- Site Name
- Erasmus Universitair Medisch Centrum Rotterdam (Erasmus MC)
- Department Name
- Neuro Oncology
- Contact Person Name
- Maarten Wijnenga
- Contact Person Email
- m.wijnenga@erasmusmc.nl
Italy
- Earliest CTIS Part Ii Submission Date
- 02-10-2025
- Latest Decision Or Authorization Date
- 07-11-2025
- Processing Time Days
- 36
- Number Of Sites
- 4
- Number Of Participants
- 41
Sites
- Site Name
- Azienda Ospedaliera Universitaria Citta Della Salute E Della Scienza Di Torino
- Department Name
- Neuro-oncology
- Contact Person Name
- Roberta Ruda
- Contact Person Email
- roberta.ruda@unito.it
- Site Name
- Azienda Ospedaliero-Universitaria Policlinico Umberto I
- Department Name
- Oncologia
- Contact Person Name
- Giuseppe Minniti
- Contact Person Email
- Giuseppe.minniti@uniroma1.it
- Site Name
- Istituto Oncologico Veneto
- Department Name
- Oncologia Medica I
- Contact Person Name
- Giuseppe Lombardi
- Contact Person Email
- giuseppe.lombardi@iov.veneto.it
- Site Name
- Instituto Di Ricovero E Cura A Carattere Scientifico
- Department Name
- Nervous System Medical Oncology
- Contact Person Name
- Enrico Franceschi
- Contact Person Email
- e.franceschi@ausl.bo.it
Belgium
- Earliest CTIS Part Ii Submission Date
- 03-10-2025
- Latest Decision Or Authorization Date
- 06-11-2025
- Processing Time Days
- 34
- Number Of Sites
- 3
- Number Of Participants
- 25
Sites
- Site Name
- UZ Brussel
- Department Name
- Department of Neurosurgery - Neuro-oncology
- Contact Person Name
- Johnny Duerinck
- Contact Person Email
- johnny.duerinck@uzbrussel.be
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Dept of Radiotherapy
- Contact Person Name
- Tom Boterberg
- Contact Person Email
- tom.boterberg@ugent.be
- Site Name
- UZ Leuven
- Department Name
- Oncology Dept
- Contact Person Name
- Paul Clement
- Contact Person Email
- Paul.Clement@uzleuven.be
Germany
- Earliest CTIS Part Ii Submission Date
- 23-10-2025
- Latest Decision Or Authorization Date
- 07-11-2025
- Processing Time Days
- 15
- Number Of Sites
- 5
- Number Of Participants
- 42
Sites
- Site Name
- Heidelberg University
- Department Name
- Neurology Clinic
- Contact Person Name
- Lukas Bunse
- Contact Person Email
- lukas.bunse@umm.de
- Site Name
- Goethe University Frankfurt
- Department Name
- Neurology -Neuro oncology
- Contact Person Name
- Michael Burger
- Contact Person Email
- burger@med.uni-frankfurt.de
- Site Name
- Universitaetsklinikum Regensburg AöR
- Department Name
- Dept. of Neurology
- Contact Person Name
- Peter Hau
- Contact Person Email
- peter.hau@ukr.de
- Site Name
- Universitaetsklinikum Bonn AöR
- Department Name
- Clin. Neurooncology Unit, Dept of Neurology
- Contact Person Name
- Ulrich Herrlinger
- Contact Person Email
- ulrich.herrlinger@ukbonn.de
- Site Name
- Universitaetsklinikum Heidelberg AöR
- Department Name
- Neurologie und Poliklinik
- Contact Person Name
- Antje Wick
- Contact Person Email
- antje.wick@med.uni-heidelberg.de
Czechia
- Earliest CTIS Part Ii Submission Date
- 02-10-2025
- Latest Decision Or Authorization Date
- 06-03-2026
- Processing Time Days
- 155
- Number Of Sites
- 1
- Number Of Participants
- 11
Sites
- Site Name
- Masarykuv Onkologicky Ustav
- Department Name
- Radiation oncology
- Contact Person Name
- Tomas Kazda
- Contact Person Email
- tomas.kazda@mou.cz
Austria
- Earliest CTIS Part Ii Submission Date
- 13-10-2025
- Latest Decision Or Authorization Date
- 04-05-2026
- Processing Time Days
- 203
- Number Of Sites
- 3
- Number Of Participants
- 21
Sites
- Site Name
- Medical University Of Vienna
- Department Name
- Innere Med 1 Abt oncologie
- Contact Person Name
- Matthias Preusser
- Contact Person Email
- matthias.preusser@meduniwien.ac.at
- Site Name
- Medizinische Universitaet Innsbruck
- Department Name
- Neurosurgery
- Contact Person Name
- Christian Freyschlag
- Contact Person Email
- christian.freyschlag@tirol-kliniken.at
- Site Name
- Kepler Universitaetsklinikum GmbH
- Department Name
- Neurology and Neurooncology
- Contact Person Name
- Annette Leibetseder-Zeller
- Contact Person Email
- Annette.Leibetseder-Zeller@kepleruniklinikum.at
Sponsor
Primary sponsor
- Full Name
- Europese Organisatie Voor Onderzoek En Behandeling Van Kanker Organisation Europeenne Pour La Recherche Et Le Traitement Du Cancer European Organi
- Organisation Type
- Patient organisation/association
- Country Of Registered Address
- Belgium
Third parties
- {"country":"Belgium","full_name":"Tamara Sals Clinical Expertise","duties_or_roles":"Monitoring in Belgium and Netherlands; sponsor duties codes include 1 and 15","organisation_type":"Pharmaceutical company"}
- {"country":"Netherlands","full_name":"Amsterdam UMC Stichting","duties_or_roles":"Tasks related to the neurocognitive function testing (sponsor duty code 15)","organisation_type":"Patient organisation/association"}
- {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"Sponsor duty code 4","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"United Kingdom","full_name":"Klinikos Limited","duties_or_roles":"Monitoring in Austria, Germany, Switzerland, France, Italy, Czech Republic (sponsor duties codes 1 and 15)","organisation_type":"Pharmaceutical company"}
- {"country":"France","full_name":"TrialPEX","duties_or_roles":"Reimbursement of patients expenses in France (sponsor duty code 15)","organisation_type":"Industry"}
- {"country":"France","full_name":"Cryoport France","duties_or_roles":"Biobanking, Shipment of samples (sponsor duty code 15)","organisation_type":"Pharmaceutical company"}
- {"country":"Spain","full_name":"Alcura Health Espana S.A.","duties_or_roles":"Sponsor duty code 14","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- S95032/AG-881 (10 mg formulation)
- Active Substance
- VORASIDENIB
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- prodAuthStatus 1
- Orphan Designation
- Yes
- Dose Levels
- 10 mg (formulation listed)
- Maximum Dose
- 40 mg (max daily dose amount)
- Investigational Product Name
- S95032/AG-881 (40 mg formulation)
- Active Substance
- VORASIDENIB
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- Oral
- Authorisation Status
- prodAuthStatus 1
- Orphan Designation
- Yes
- Dose Levels
- 40 mg (formulation listed)
- Maximum Dose
- 40 mg (max daily dose amount)
- Investigational Product Name
- Placebo tablets to match S95032 drug product
- Modality
- Other
- Routes Of Administration
- Oral
- Route
- Oral
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