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IDH1-mutant GliomaPhase 1/2NCT06478212

Vorasidenib in Combination With Temozolomide (TMZ) in IDH-mutant Glioma

A Phase 1/2 study testing Vorasidenib and Temozolomide (TMZ) in people with IDH1-mutant Glioma and IDH2-mutant Glioma, run by Institut de Recherches Internationales Servier at 28 sites in 11 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

The objective of this study is to determine the safety and tolerability of vorasidenib in combination with temozolomide (TMZ) and to establish the recommended combination dose (RCD) of vorasidenib. Read more about this study

Who is it for?
Ages 12 years and older
Conditions the study is for
IDH1-mutant Glioma, IDH2-mutant Glioma
What is being tested?
Vorasidenib and Temozolomide (TMZ)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
51 participants
Where
28 sitesin 11 countries
Study dates
22 Jan 2025to Jun 2028
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 12 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Be ≥12 years of age with a weight at screening ≥40 kg.
  • Have documented IDH1 or IDH2 mutation based on local testing of tumor tissue by an accredited laboratory
  • Have adequate renal function, defined as a creatinine clearance ≥40 mL/min based on the Cockcroft-Gault glomerular filtration rate estimation: (140 - Age) × (Weight in kg) × (0.85 if female) / 72 × serum creatinine (mg/dL).
  • Have adequate bone marrow function as evidenced by:
  • Absolute neutrophil count ≥1,500/mm3 or 1.5×109/L
  • Hemoglobin ≥9 g/dL or 90 g/L
Show all 28Show fewer
  • Platelets ≥100,000/mm3 or 100×109/L
  • Have expected survival of ≥3 months.
  • KPS or LPPS ≥70 at the start of study treatment.
  • Participants on corticosteroids for reasons related to glioma must be on a stable or decreasing dose (≤4mg/day dexamethasone or equivalent) for ≥5 days before the start of study treatment.
  • Female participants of reproductive potential must have a negative serum pregnancy test before starting study treatment.
  • Phase 1b ONLY:
  • Have histologically confirmed Grade 2, 3 or 4 IDHm (as per WHO 2021) glioma (astrocytoma or oligodendroglioma).
  • For oligodendroglioma: Have local testing at an accredited laboratory demonstrating presence of 1p19q co deletion
  • For astrocytoma: Have local testing by an accredited laboratory demonstrating lack of 1p19q co-deletion and/or documented loss of nuclear ATRX expression or ATRX mutation
  • Are appropriate to receive TMZ as post-radiotherapy (RT) adjuvant therapy or as treatment for first disease recurrence after prior RT and/or chemotherapy, per Investigator judgement. For those receiving TMZ in the post-RT adjuvant setting, study treatment must begin no more than 6 weeks after completion of RT.
  • Have adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤1.5×upper limit of normal (ULN); if ≥1.5×ULN and due to Gilbert syndrome, total bilirubin ≤3×ULN with direct bilirubin ≤ULN,
  • AST and ALT ≤ULN, and
  • Alkaline phosphatase ≤2.5×ULN.
  • Phase 2 ONLY:
  • Have histologically confirmed Grade 4 astrocytoma, IDHm (per 2021 WHO criteria). Those who meet the Grade 4 designation via homozygous deletion of CDKN2A/B are eligible.
  • Have absence of 1p19q co-deletion (i.e., non-co-deleted, or intact) and/or documented loss of nuclear ATRX expression or ATRX mutation by local testing.
  • Have received SOC RT with concurrent TMZ (RT-TMZ) before enrollment. Study treatment must begin no more than 6 weeks after completion of RT-TMZ.
  • Have adequate hepatic function as evidenced by:
  • Serum total bilirubin ≤1.5×ULN; if ≥1.5×ULN and due to Gilbert syndrome, total bilirubin ≤3×ULN with direct bilirubin ≤ULN,
  • AST and ALT at or below the upper limit of normal. An elevation ≤1.5×ULN and considered not clinically significant by the Investigator may be allowed after Medical Monitor (Sponsor) approval, and
  • Alkaline phosphatase ≤2.5×ULN.

Who cannot join

  • Unable to swallow oral medication.
  • Are pregnant or breastfeeding.
  • Are participating in another interventional study at the same time; participation in non-interventional registries or epidemiological studies is allowed.
  • Have leptomeningeal disease.
  • Have a known coagulopathy.
  • Received prior therapy with an IDH inhibitor, IDH-directed vaccine, or bevacizumab.
Show all 26Show fewer
  • Have a history of another concurrent primary cancer, with the exception of:
  • curatively resected non-melanoma skin cancer, or
  • curatively treated carcinoma in situ. Participants with other previously treated malignancies are eligible provided they have been disease-free for 3 years at Screening.
  • Have a known diagnosis of replication repair-deficient glioma (e.g., a known diagnosis of constitutional mismatch repair deficiency or Lynch syndrome).
  • Have a known hypersensitivity to any of the components or metabolites of vorasidenib or TMZ.
  • Have significant active cardiac disease within 6 months before Screening, including New York Heart Association (NYHA) Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
  • Have heart rate corrected QT interval (using Fridericia's formula) (QTcF) ≥450 msec or have other factors that increase risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome). Right bundle branch block and prolonged QTcF interval may be permitted based on local cardiology assessment.
  • Have known active hepatitis B (HBV) or hepatitis C (HCV) infections, known positive human immunodeficiency virus (HIV) antibody results, or acquired immunodeficiency syndrome (AIDS) related illness. Participants with a sustained viral response to HCV treatment or immunity to prior HBV infection will be permitted. Participants with chronic HBV or HIV that is adequately suppressed per institutional practice will be permitted.
  • Phase 1b ONLY:
  • For those receiving TMZ in the frontline post-RT adjuvant setting: Have progressive disease during RT or after completion of SOC RT and before the start of study treatment.
  • For those receiving TMZ in the recurrent disease setting:
  • Have received prior systemic anti-cancer therapy (other than surgery) within 1 month (or 6 weeks for nitrosoureas and 6 months for TMZ) of the start of study treatment. In addition, the first dose of study treatment should not occur before a period of 28 days or ≥5 half-lives of any prior investigational agent have elapsed, whichever is longer.
  • Have received more than one prior line of therapy for glioma (Note: prior RT + chemotherapy is considered one line of therapy).
  • Had Grade ≥2 hepatic-related toxicity (AST, ALT, and/or bilirubin elevations) during prior systemic chemotherapy
  • Had Grade 4 hematologic toxicity (excluding lymphopenia) that did not recover within 7 days during a prior course of TMZ
  • Phase 2 ONLY:
  • Have received any other glioma-directed therapy other than surgery and SOC RT-TMZ
  • Have progressive disease during RT-TMZ or after completion of SOC RT-TMZ and before the start of study treatment.
  • Had Grade 4 hematologic toxicity (excluding lymphopenia) that did not recover within 7 days during concurrent RT-TMZ
  • Had Grade ≥2 hepatic-related toxicity (AST, ALT, and/or bilirubin elevations) during concurrent RT-TMZ

Trial locations and contacts

28 sites in 11 countries.

28 sites in 11 countries

United States6 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • MD Anderson Cancer Center

    Houston, Texas, 77030

  • University of California Los Angeles

    Los Angeles, California, 90095

  • University of Miami

    Miami, Florida, 33136

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

Japan4 sites

  • Kumamoto University Hospital

    Kumamoto, 860-8556

  • Kyoto University Hospital

    Kyoto, 606-8507

  • Nagoya University Hospital

    Nagoya, 466-8550

  • National Cancer Center Hospital

    Tokyo, 104-0045

Other trials in Japan

France3 sites

  • Hôpital Pierre Wertheimer

    Lyon, 69003

  • Hôpital Pitié-Salpêtrière

    Paris, 75013

  • IUCT-Oncopole Institut Universitaire du Cancer

    Toulouse, 31059

Other trials in France

Germany3 sites

  • Universitätsklinikum Heidelberg

    Heidelberg, 69120

  • Medizinische Fakultät Mannheim, Universität Heidelberg

    Mannheim, 68167

  • Universitätsklinikum Regensburg

    Regensburg, 93053

Other trials in Germany

Italy3 sites

  • IOV - Ospedale Busonera

    Padua, 35128

  • Instituto Clinico Humanitas IRCCS

    Rozzano, Milan, 20089

  • Ospedale Molinette - Centro Oncologico Ematologico

    Turin, 10126

Other trials in Italy

China2 sites

  • Beijing Tiantan Hospital, Capital Medical University

    Beijing, 100050

  • Huashan Hospital, Fudan University

    Shanghai, 200040

Other trials in China

Spain2 sites

  • H. Valle de Hebron

    Barcelona, 08035

  • Hospital 12 de Octubre

    Madrid, 28041

Other trials in Spain

United Kingdom2 sites

  • Christie Hospital

    Manchester, M20 4BX

  • The Royal Marsden in Sutton

    Sutton, SM2 5PT

Other trials in United Kingdom

Austria1 site

  • Medical University of Vienna - AKH

    Vienna, 01090

Other trials in Austria

Israel1 site

  • The Tel Aviv Sourasky Medical Center (TASMC) (Ichilov Hospital)

    Tel Aviv, 64239

Other trials in Israel

Netherlands1 site

  • Erasmus MC

    Rotterdam, 503015

Other trials in Netherlands

About this study

Official title: A Phase 1b/2, Multicenter Study of Vorasidenib in Combination With Temozolomide (TMZ) in Participants With IDH1- or IDH2-mutant Glioma

The objective of this study is to determine the safety and tolerability of vorasidenib in combination with temozolomide (TMZ) and to establish the recommended combination dose (RCD) of vorasidenib. The study will begin as a Phase Ib study to determine the RCD and then will transition to a Phase II study to assess the clinical efficacy of vorasidenib at the RCD in combination with TMZ. During the treatment period participants will have study visits on day 1 and 22 of each cycle, with additional visits occurring during the first cycle of the Phase 1b study. Approximately 30 days after treatment has ended, a safety follow-up visit will occur and then participants will be followed for survival every 3 months. Study visits may include questionnaires, blood tests, ECG, vital signs, and a physical examination.

Being tested
Vorasidenib, Temozolomide (TMZ)
Keywords
IDH-mutant glioma, IDH mutation, vorasidenib, S95032, Phase 1/2, pediatric

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VorasidenibDrug

    To be taken by mouth once daily in 28-day cycles with no break between cycles

  • Temozolomide (TMZ)Drug

    To be taken by mouth once daily for the first 5 days of each 28-day cycle, for a maximum of 12 cycles

Study groups in NCT06478212
Study groupRoleWhat they receive
Phase 1b: Vorasidenib and Temozolomide (TMZ)ExperimentalNot described
Receives: Drug: Vorasidenib; Drug: Temozolomide (TMZ)
Phase 2: Vorasidenib recommended combination dose (RCD) and Temozolomide (TMZ)ExperimentalNot described
Receives: Drug: Vorasidenib; Drug: Temozolomide (TMZ)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase 1b ONLY: Dose-limiting toxicities (DLTs)

    Measured: Through cycle 1 (each cycle is 28 days)

  2. Number and severity of adverse events (AEs), serious adverse events (SAEs), and AEs of special interest (AESIs)

    Measured: Through 30 days after the end of treatment (Approximately 3 years)

  3. Progression-free Survival (PFS) status at 12 months

    Measured: 12 months after treatment initiation

Secondary outcomes (14)

  1. PFS

    Measured: Through study completion (Approximately 3 years)

  2. Overall survival (OS)

    Measured: Through study completion (Approximately 3 years)

  3. Objective response rate (ORR)

    Measured: Through study completion (Approximately 3 years)

  4. Clinical benefit rate (CBR) (CR+partial response [PR]+stable disease [SD])

    Measured: Through study completion (Approximately 3 years)

  5. Plasma concentration of vorasidenib and its metabolite AGI-69460

    Measured: Through cycle 13 (each cycle is 28 days)

  6. Phase 1b ONLY: Plasma concentration of TMZ

    Measured: Through cycle 2 (each cycle is 28 days)

  7. Area under the curve (AUC) of vorasidenib and its metabolite AGI-69460

    Measured: Through cycle 13 (each cycle is 28 days)

  8. Time to maximum concentration (Tmax) of vorasidenib and its metabolite AGI-69460

    Measured: Through cycle 13 (each cycle is 28 days)

  9. Maximum concentration (Cmax) of vorasidenib and its metabolite AGI-69460

    Measured: Through cycle 13 (each cycle is 28 days)

  10. Trough concentration (Ctrough) of vorasidenib and its metabolite AGI-69460

    Measured: Through cycle 13 (each cycle is 28 days)

  11. Phase 1b ONLY: Area under the curve (AUC) of TMZ

    Measured: Through cycle 2 (each cycle is 28 days)

  12. Phase 1b ONLY: Time to maximum concentration (Tmax) of TMZ

    Measured: Through cycle 2 (each cycle is 28 days)

  13. Phase 1b ONLY: Maximum concentration (Cmax) of TMZ

    Measured: Through cycle 2 (each cycle is 28 days)

  14. Phase 1b ONLY: Trough concentration (Ctrough) of TMZ

    Measured: Through cycle 2 (each cycle is 28 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jun 2024
  2. Study start22 Jan 2025
  3. Primary completionNov 2027 (estimated)
  4. Study completionJun 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
51 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06478212
Sponsor's protocol ID
S095032-211
Status last verified
Jul 2026
First submitted
17 Jun 2024
Last updated
8 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
Expanded access
Available

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Vorasidenib and Temozolomide (TMZ) in people with IDH1-mutant Glioma and IDH2-mutant Glioma, run by Institut de Recherches Internationales Servier at 28 sites in 11 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 28 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States, Japan, France, Germany, Italy and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase 1b ONLY: Dose-limiting toxicities (DLTs) (time frame: Through cycle 1 (each cycle is 28 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06478212.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.

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