Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma
A Phase 1, Safety Lead-In and Randomized, Open-label, Perioperative Study of Vorasidenib in Combination With Pembrolizumab in Subjects With Recurrent or Progressive IDH-1 Mutant Glioma
2 other identifiers
interventional
60
1 country
17
Brief Summary
Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jan 2023
Longer than P75 for phase_1
17 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 21, 2022
CompletedFirst Posted
Study publicly available on registry
August 2, 2022
CompletedStudy Start
First participant enrolled
January 20, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 12, 2026
CompletedStudy Completion
Last participant's last visit for all outcomes
August 30, 2027
ExpectedMarch 12, 2026
March 1, 2026
3.1 years
July 21, 2022
March 11, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Safety Lead-in Phase: Percentage of Participants With Dose-limiting Toxicities (DLTs)
First 21 days of dosing (Cycle 1) in safety lead-in phase
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
approximately up to 19 months
Percentage of Tumor-infiltrating Lymphocyte (TIL) Cells in Surgically Resected Tumors Following Treatment With Vorasidenib + Pembrolizumab Compared to Untreated Control Tumors
TIL is defined as the percentage of tumor-infiltrating lymphocyte cells on a logarithmic scale.
approximately 2 months
Secondary Outcomes (7)
Overall Survival (OS)
Up to approximately 55 months
AUC: Area Under the Plasma Concentration-Time Curve of Vorasidenib
approximately 16 months
Cmax: Maximum Observed Plasma Concentration of Vorasidenib
approximately 16 months
Concentration of 2-hydroxygluarate (2-HG) in Surgically Resected Tumors
approximately 2 months
Concentration of Vorasidenib in Surgically Resected Tumors
approximately 2 months
- +2 more secondary outcomes
Study Arms (4)
Safety Lead-In Phase: Vorasidenib + Pembrolizumab
EXPERIMENTALParticipants will receive vorasidenib orally, once daily (QD) in combination with pembrolizumab 200 mg intravenous (IV) infusion, once every 3 weeks (Q3W) in each 21-day cycle until disease progression, unacceptable toxicity or other discontinuation criteria are met.
Randomized Perioperative Phase: Vorasidenib + Pembrolizumab
EXPERIMENTALParticipants will receive vorasidenib recommended combination dose (RCD) determined in the Safety Lead-in phase, orally, QD from Day 1 to 28 in combination with pembrolizumab 200 mg IV infusion, Q3W on Days 1 and 22 of a 28-day cycle prior to surgery.
Randomized Perioperative Phase: Vorasidenib Only
EXPERIMENTALParticipants will receive vorasidenib orally, QD from Day 1 to 28 of a 28-day cycle prior to surgery.
Randomized Perioperative Phase: Untreated Control Group
NO INTERVENTIONParticipants will not receive any treatment prior to surgery.
Interventions
Administered orally as tablets.
Administered as IV infusion.
Eligibility Criteria
You may qualify if:
- Have Karnofsky Performance Status (KPS) of ≥ 70%.
- Have expected survival of ≥ 3 months.
- Have histologically confirmed Grade 2 or Grade 3 glioma (per the 2016 or 2021 World Health Organization \[WHO\] Classification of Tumors of the central nervous system)
- Have:
- Documented IDH1-R132H gene mutation; and
- Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrast enhancing disease as determined by institutional radiologist/Investigator at Screening on either 2D T1 post-contrast weighted images or 3D T1 post-contrast weighted images. Per mRANO criteria, measurable lesion is defined as at least 1 enhancing lesion measuring ≥ 1 cm x ≥ 1 cm. OR (in the absence of measurable enhancing disease) measurable, MRI-evaluable, unequivocal non enhancing disease as determined by institutional radiologist/Investigator at Screening on either 2D or 3D T2-weighted image or FLAIR. Per RANO 2.0 criteria, measurable lesion is defined as at least 1 non enhancing lesion measuring ≥ 1 cm × ≥ 1 cm.
- Have recurrent or progressive disease and received prior treatment with chemotherapy, radiation, or both.
- Surgical resection is indicated for treatment, but surgery is not urgently indicated (e.g., for whom surgery within the next 6-9 weeks is appropriate). (NOTE: This criterion only applies to participants enrolled in the perioperative phase of the study. Participants in the Safety Lead-In should not require surgery).
You may not qualify if:
- Have received prior systemic anti-cancer therapy within 1 month of the first dose of IMP, radiation within 12 months of the first dose of IMP, or an investigational agent \< 14 days prior to the first dose of IMP. In addition, the first dose of IMP should not occur before a period of ≥ 5 half-lives of the investigational agent has elapsed.
- Have received 2 or more courses of radiation.
- Have received any prior treatment with an isocitrate dehydrogenase (IDH) inhibitor; anti-programmed cell death 1 (PD1), anti-programmed cell death ligand 1 (PD-L1), or anti-PD-ligand 2 (L2) agent, or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX 40, CD137); any other checkpoint inhibitor; bevacizumab; or any prior vaccine therapy.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (17)
University of Alabama at Birmingham
Birmingham, Alabama, 35249, United States
University of California, Los Angeles (Site: 840113)
Los Angeles, California, 90095, United States
University of California, San Francisco (Site: 840149)
San Francisco, California, 94013, United States
University of Colorado
Aurora, Colorado, 80045, United States
University of Miami (Site: 840129)
Miami, Florida, 33136, United States
Northwestern University (Site: 840123)
Chicago, Illinois, 60045, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Massachusetts General Hospital (Site: 840104)
Boston, Massachusetts, 02114, United States
Dana-Farber Cancer Institute (Site: 840139)
Boston, Massachusetts, 02215, United States
University of Michigan
Ann Arbor, Michigan, 48109, United States
Memorial Sloan Kettering Cancer Center (Site: 840117)
New York, New York, 10017, United States
Duke University (Site: 840110)
Durham, North Carolina, 27705, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Mayo Clinic Florida
Cleveland, Ohio, 44195, United States
University of Pennsylvania Health System
Philadelphia, Pennsylvania, 19104, United States
MD Anderson Cancer Center (Site: 840102)
Houston, Texas, 77030, United States
University of Utah, Huntsman Cancer Center
Salt Lake City, Utah, 84112, United States
Related Publications (1)
Wen P, Peters K, de la Fuente M, Mellinghoff I, Arrillaga-Romany I, Kumthekar P, Clarke J, Puduvalli V, de Groot J, Zhang J, Chisamore M, Abshire M, Mahboub P, Hassan I, Knipstein J, Cloughesy T. Phase 1 Safety Lead-in and Randomized Open-label Perioperative Study of Vorasidenib Combined with Pembrolizumab in Recurrent or Progressive Enhancing IDH1-mutant Astrocytomas: Safety Lead-in Results. Neuro Oncol. 2023 Nov 10;25(Supplement_5):V65. doi: https://doi.org/10.1093/neuonc/noad179.0254
BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 21, 2022
First Posted
August 2, 2022
Study Start
January 20, 2023
Primary Completion
February 12, 2026
Study Completion (Estimated)
August 30, 2027
Last Updated
March 12, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorisation 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.
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * Used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * Where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * Sponsored by Servier * With a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.