Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)

Study Overview
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Brief Summary
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Study AG881-C-004 is a phase 3, multicenter, randomized, double-blind, placebo-controlled study comparing the efficacy of vorasidenib to placebo in participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation who have undergone surgery as their only treatment. Participants will be required to have central confirmation of IDH mutation status prior to randomization. Approximately 340 participants are planned to be randomized 1:1 to receive orally administered vorasidenib 40 mg QD or placebo.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Placebo-Controlled Study of AG-881 in Subjects With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation

Conditions
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Grade 2 Glioma, Residual Glioma, Recurrent Glioma

Intervention / Treatment
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* Drug: Vorasidenib
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Be at least 12 years of age and weigh at least 40 kg. Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria. Have had at least 1 prior surgery for glioma (biopsy, sub-total resection, gross-total resection), with the most recent surgery having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before the date of randomization, and no other prior anticancer therapy, including chemotherapy and radiotherapy and not be in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator. Have confirmed IDH1 (IDH1 R132H/C/G/S/L mutation variants tested) or IDH2 (IDH2 R172K/M/W/S/G mutation variants tested) gene mutation status disease by central laboratory testing during the Prescreening period and available 1p19q status by local testing (eg, fluorescence in situ hybridization [FISH], comparative genomic hybridization [CGH] array, sequencing) using an accredited laboratory. Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC. Have a Karnofsky Performance Scale (KPS) score (for participants ≥16 years of age) or Lansky Play Performance Scale (LPPS) score (for participants <16 years of age) of ≥80%. Key Exclusion Criteria: Have had any prior anticancer therapy other than surgery (biopsy, sub-total resection, gross-total resection) for treatment of glioma including systemic chemotherapy, radiotherapy, vaccines, small-molecules, IDH inhibitors, investigational agents, laser ablation, etc. Have features assessed as high-risk by the Investigator, including brainstem involvement either as primary location or by tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor in the opinion of the Investigator (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with activities of daily life AND failed 3 lines of antiepileptic drug regimens including at least 1 combination regimen).

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants randomized in a 1:1 allocation (vorasidenib vs Placebo)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vorasidenib<br>Vorasidenib 40 mg, continuous daily dosing. | Drug: Vorasidenib<br>* Vorasidenib oral film-coated tablets<br>* Other names: AG-881;|
| Placebo Comparator: Matching Placebo<br>Matching placebo 40 mg, continuous daily dosing. | Drug: Matching Placebo<br>* Matching Placebo oral tablets<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS) | PFS is defined as the time from date of randomization to date of first documented radiographic PD (as assessed by the blinded independent review committee (BIRC) per modified Response Assessment for Neuro-oncology for Low-Grade Gliomas or date of death due to any cause, whichever occurs earlier. | Up to approximately 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Next Intervention |  | Up to approximately 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AG-881