A Phase 1b/2, multicenter study of vorasidenib in combination with temozolomide (TMZ) in participants with IDH1- or IDH2-mutant glioma (S095032 (AG-881))
- Conditions
- IDH1- or IDH2-mutant glioma
- Registration Number
- jRCT2031240734
- Lead Sponsor
- Institut de Recherches Internationales Servier
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 10
Males or non-pregnant and non-lactating females aged 12 years or older with a weight of 40 kg or more at screening.
Have documented IDH1 or IDH2 mutation based on local testing of tumor tissue by an accredited laboratory.
Have adequate renal, bone marrow and hepatic function.
KPS or LPPS of 70 or higher at the start of study treatment.
Additional Inclusion Criteria for Phase 1b:
Have histologically confirmed Grade 2, 3 or 4 IDHm (as per WHO 2021) glioma (astrocytoma or oligodendroglioma).
Are appropriate to receive TMZ as post- RT adjuvant therapy or as treatment for first disease recurrence after prior RT and/or chemotherapy, per Investigator judgment.
Additional Inclusion Criteria for Phase 2:
Have histologically confirmed Grade 4 astrocytoma, IDHm (per 2021 WHO criteria).
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.
Unable to swallow oral medication.
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.
Have a known diagnosis of replication repair-deficient glioma (e.g., a known diagnosis of constitutional mismatch repair deficiency or Lynch syndrome).
Have significant active cardiac disease within 6 months before Screening, including New York Heart Association Class III or IV congestive heart failure, myocardial infarction, unstable angina, and/or stroke.
Have a heart rate corrected QT interval (using Fridericia's formula) (QTcF) 450 msec or higher or have other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome).
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, or chronic HBV or HIV that are adequately suppressed per institutional practice will be permitted.
Have known active inflammatory gastrointestinal disease, chronic diarrhea, previous gastric resection or lap band, dysphagia, short-gut syndrome, gastroparesis, or other conditions that limit the ingestion or gastrointestinal absorption of drugs administered orally. Gastroesophageal reflux disease under medical treatment is allowed (assuming no drug interaction potential).
Additional Exclusion Criteria for Phase 2:
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.
Study & Design
- Study Type
- Interventional
- Study Design
- single assignment
- Primary Outcome Measures
Name Time Method - DLTs (for Phase 1b only), incidence and severity of AEs, SAEs, and AESIs
PFS status at 12 months
- Secondary Outcome Measures
Name Time Method clinical benefit CR+ PR+SD
Plasma concentrations Plasma concentrations of vorasidenib and its metabolite AGI-69460 and TMZ
PK parameters PK parameters of vorasidenib and its metabolite AGI-69460 and TMZ