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

NCT06780930 | Active Not Recruiting Phase 3 DMC

• 1 other identifier: CL3-95032-016
• Study Type: interventional
• Target: 57
• Locations: 2 countries
• Sites: 8

Brief Summary

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.

Conditions

Residual or Recurrent Grade 2 IDH Mutant Glioma

Outcome Measures

Primary Outcomes (1)

• 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.

  Approximately 1.5 years

Secondary Outcomes (11)

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

  Through Cycle 1 (28 days)

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

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

• Severity of AEs

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

• Time-To-Next-Intervention (TTNI)

  Through the PFS Follow-up (approximately 6.5 years)

• Tumor Growth Rate (TGR) as assessed by volume

  Through the PFS Follow-up (approximately 6.5 years)

Study Arms (2)

Randomized Double-Blind Phase: Vorasidenib

EXPERIMENTAL

Drug: Vorasidenib

Randomized Double-Blind Phase: Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Placebo DRUG

For oral administration once daily

Randomized Double-Blind Phase: Placebo

Vorasidenib DRUG

For oral administration once daily

Randomized Double-Blind Phase: Vorasidenib

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Servier: lead

Study Sites (8)

The Second People's Hospital of Shenzhen

Shenzhen, Guangdong, China

Location

West China Hospital Sichuan University

Chengdu, Sichuan, China

Location

Tiantan Hospital

Beijing, 100070, China

Location

Sanbo Brain Hospital, Capital Medical University

Beijing, China

Location

Huashan Hospital Fudan University

Shanghai, 200040, China

Location

The Second Affiliated Hospital of Air Force Military Medical University

Xi'an, China

Location

Taipei Veterans General Hospital

Taipei, Taiwan

Location

Chang Gung Memorial Hospital,

Taoyuan District, Taiwan

Location

MeSH Terms

Interventions

vorasidenib

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2024
• First Posted: January 17, 2025
• Study Start: October 18, 2024
• Primary Completion: October 2, 2025
• Study Completion (Estimated): October 31, 2030
• Last Updated: January 9, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: After Marketing Authorization in EEA or US if the study is used for the approval.
• Access Criteria: Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.

Locations

TW (2); CN (6)