Phase 3 Study of Vorasidenib (S095032/AG-881) in Asian Participants With Residual or Recurrent Grade 2 Glioma With an IDH1 orIDH2 Mutation

Phase 3Active Not RecruitingNCT06780930

Servier57 enrolled

Overview

The objective of this study is to determine the efficacy, safety, and pharmacokinetics of vorasidenib in Asian participants with residual or recurrent Grade 2 glioma with an IDH1 or IDH2 mutation. The study will begin with a safety lead-in (SLI) phase and then will transition to a randomized double-blind placebo-controlled phase. During the study participants will have study visits on day 1 and 15 of the first two cycles, and then only on day 1 of treatment cycles in the frequency included in the study schedule of assessments. All participants will have an end of treatment visit within 7 days after their last dose of study treatment. Approximately 28 (+5) days after treatment has ended, a safety follow-up visit will occur. Study visits may include questionnaires, blood tests, ECG, vital signs, and a physical examination. Beginning at the end of treatment visit participants will be contacted by phone every 6 months for overall survival up to 5 years after the last participant is randomized or until death, withdrawal of consent from overall study participation, lost to follow-up, or sponsor ending the study, whichever occurs first.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Residual or Recurrent Grade 2 IDH Mutant Glioma

Interventions

Eligibility

Sex: ALLMin age: 12 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Be at least 12 years of age (for Randomized Double-Blind phase) and weigh at least 40 kg. * 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%. * Have Grade 2 oligodendroglioma or astrocytoma per WHO 2016 criteria. * Have had at least 1 prior surgery for glioma with the most recent one having occurred at least 1 year (-1 month) and not more than 5 years (+3 months) before randomization, and no other prior anticancer therapy, including radiotherapy and not be in need of immediate chemotherapy or radiotherapy. * 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 * Have MRI-evaluable, measurable, non-enhancing disease, as confirmed by the BIRC for double blind part. 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. * Concurrent active malignancy except for a) curatively resected nonmelanoma skin cancer or b) curatively treated carcinoma in situ. Participants with previously treated malignancies are eligible provided they have been disease-free for 3 years at Screening. * Have any other acute or chronic medical or psychiatric condition that may increase the risk associated with the study participation or investigational product administration or may interfere with the interpretation of study results. * Have known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, known positive human immunodeficiency virus antibody results, or 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 that is adequately suppressed by institutional practice will be permitted.

Locations (8)

The Second People's Hospital of Shenzhen

Shenzhen, Guangdong, China

West China Hospital Sichuan University

Chengdu, Sichuan, China

Tiantan Hospital

Beijing, China

Sanbo Brain Hospital, Capital Medical University

Beijing, China

Huashan Hospital Fudan University

Shanghai, China

The Second Affiliated Hospital of Air Force Military Medical University

Xi'an, China

Taipei Veterans General Hospital

Taipei, Taiwan

Chang Gung Memorial Hospital,

Taoyuan District, Taiwan

Outcomes

Primary Outcomes

Progression-Free Survival (PFS)

The time from date of randomization to date of first documented radiographic progressive disease (PD), as assessed by the Blinded Independent Review Committee (BIRC), or date of death due to any cause, whichever occurs earlier.

Time frame: Approximately 1.5 years

Secondary Outcomes

Dose limiting toxicities (DLTs) (for open-label Safety Lead In (SLI) phase)

Time frame: Through Cycle 1 (28 days)

Number of adverse events (AEs), serious adverse events (SAEs), and AEs leading to discontinuation or death

Time frame: Through the safety follow up visit, 28 days after the last dose (approximately 6.5 years)

Severity of AEs

Time frame: Through the safety follow up visit, 28 days after the last dose (approximately 6.5 years)

Time-To-Next-Intervention (TTNI)

The time from randomization to the initiation of the first subsequent anticancer therapy (including vorasidenib, for participants randomized to placebo who subsequently cross over) or death due to any cause.