Home › Trials › NCT06478212

Vorasidenib combined with Temozolomide for treating IDH-mutant Glioma

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

Phase1; Phase2 Interventional Servier · NCT06478212

This study is testing if combining a new drug called vorasidenib with temozolomide can safely help people with IDH-mutant gliomas.

Quick facts

PhasePhase1; Phase2
Study typeInterventional
Enrollment42 (estimated)
Ages12 Years and up
SexAll
SponsorServier Industry-sponsored
Drugs / interventionsbevacizumab, chemotherapy
Locations32 sites (Los Angeles, California and 31 other locations)
Trial IDNCT06478212 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety and tolerability of vorasidenib when used alongside temozolomide (TMZ) in patients with IDH1 or IDH2 mutant gliomas. Initially, it will conduct a Phase Ib assessment to determine the recommended combination dose (RCD) of vorasidenib, followed by a Phase II evaluation of its clinical efficacy at that dose. Participants will undergo regular study visits for monitoring, including blood tests and physical examinations, throughout the treatment and follow-up periods.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 12 and older with documented IDH1 or IDH2 mutations and adequate organ function.

Not a fit: Patients without IDH mutations or those with severe comorbidities may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with IDH-mutant gliomas, potentially improving their outcomes.

How similar studies have performed: Other studies have shown promise in targeting IDH mutations, suggesting potential for success with this approach.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

* 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:

  1. Absolute neutrophil count ≥1,500/mm3 or 1.5×109/L
  2. Hemoglobin ≥9 g/dL or 90 g/L
  3. 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).

  1. For oligodendroglioma: Have local testing at an accredited laboratory demonstrating presence of 1p19q co deletion
  2. 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:

  1. 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,
  2. AST and ALT ≤ULN, and
  3. 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:

  1. Serum total bilirubin ≤1.5×ULN; if ≥1.5×ULN and due to Gilbert syndrome, total bilirubin ≤3×ULN with direct bilirubin ≤ULN,
  2. 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
  3. Alkaline phosphatase ≤2.5×ULN.

Exclusion Criteria:

* 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.
* Have a history of another concurrent primary cancer, with the exception of:

  1. curatively resected non-melanoma skin cancer, or
  2. 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:

  1. 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.
  2. 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

Where this trial is running

Los Angeles, California and 31 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions IDH1-mutant GliomaIDH2-mutant GliomaIDH-mutant gliomaIDH mutationvorasidenibS95032Phase 1/2pediatric
Last reviewed 2026-06-10 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.