Study of Vorasidenib (AG-881) in Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 or IDH2 Mutation (INDIGO)
Condition: Grade 2 Glioma; Residual Glioma; Recurrent Glioma
MeSH terms: Glioma; Recurrence
Intervention: Vorasidenib; Matching Placebo
Intervention description: Vorasidenib oral film-coated tablets; Matching Placebo oral tablets
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants randomized in a 1:1 allocation (vorasidenib vs Placebo)
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 331.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: AG-881

Summary:

      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.
    

Eligibility criteria:

        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).