Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma

NCT ID: NCT05484622

Last Updated: 2025-10-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

72 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-20

Study Completion Date

2027-08-30

Brief Summary

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Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.

Detailed Description

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The study is divided into 2 phases, a Safety Lead-In phase and a randomized perioperative phase. In the Safety Lead-In Phase, the recommended combination dose (RCD) of vorasidenib will be determined. In the Randomized Perioperative Phase, the Lymphocytes infiltration in tumors will be evaluated following pre-surgical treatment with vorasidenib and pembrolizumab combination, compared to untreated control tumors. Prior to surgery, participants will be randomized to receive vorasidenib at the RCD in combination with pembrolizumab, or vorasidenib only, or no treatment (untreated control group). Following surgery, participants will have the option to receive treatment with vorasidenib in combination with pembrolizumab in 21-day cycles.

Study treatment will be administered until participant experiences unacceptable toxicity, disease progression, or other discontinuation criteria are met.

Conditions

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Astrocytoma Oligodendroglioma

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Sequential design for safety lead-in and randomized perioperative phases, parallel design within randomized perioperative phase.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Safety Lead-In Phase: Vorasidenib + Pembrolizumab

Participants 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.

Group Type EXPERIMENTAL

Vorasidenib

Intervention Type DRUG

Administered orally as tablets.

Pembrolizumab

Intervention Type DRUG

Administered as IV infusion.

Randomized Perioperative Phase: Vorasidenib + Pembrolizumab

Participants 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.

Group Type EXPERIMENTAL

Vorasidenib

Intervention Type DRUG

Administered orally as tablets.

Pembrolizumab

Intervention Type DRUG

Administered as IV infusion.

Randomized Perioperative Phase: Vorasidenib Only

Participants will receive vorasidenib orally, QD from Day 1 to 28 of a 28-day cycle prior to surgery.

Group Type EXPERIMENTAL

Vorasidenib

Intervention Type DRUG

Administered orally as tablets.

Randomized Perioperative Phase: Untreated Control Group

Participants will not receive any treatment prior to surgery.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Vorasidenib

Administered orally as tablets.

Intervention Type DRUG

Pembrolizumab

Administered as IV infusion.

Intervention Type DRUG

Other Intervention Names

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S095032 AG-881 MK-3475 KEYTRUDA® KEYNOTE-B39 MK-3475-B39

Eligibility Criteria

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Inclusion Criteria

1. Have Karnofsky Performance Status (KPS) of ≥ 70%.
2. Have expected survival of ≥ 3 months.
3. 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)
4. Have:

1. Documented IDH1-R132H gene mutation; and
2. For Astrocytomas: Absence of 1p19q co-deletion (i.e., exclusion of combined whole-arm deletions of 1p and 19q) and/or documented loss of nuclear ATRX expression or ATRX mutation by local testing. For Oligodendrogliomas: Presence of 1p19q co-deletion (i.e., combined whole-arm deletions of 1p and 19q) by local testing.
5. 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.
6. Have recurrent or progressive disease and received prior treatment with chemotherapy, radiation, or both.
7. 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).

Exclusion Criteria

1. 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.
2. Have received 2 or more courses of radiation.
3. 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role collaborator

Institut de Recherches Internationales Servier

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

University of California, Los Angeles (Site: 840113)

Los Angeles, California, United States

Site Status RECRUITING

University of California, San Francisco (Site: 840149)

San Francisco, California, United States

Site Status RECRUITING

University of Colorado

Aurora, Colorado, United States

Site Status RECRUITING

University of Miami (Site: 840129)

Miami, Florida, United States

Site Status RECRUITING

Northwestern University (Site: 840123)

Chicago, Illinois, United States

Site Status RECRUITING

Johns Hopkins University

Baltimore, Maryland, United States

Site Status RECRUITING

Massachusetts General Hospital (Site: 840104)

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute (Site: 840139)

Boston, Massachusetts, United States

Site Status RECRUITING

University of Michigan

Ann Arbor, Michigan, United States

Site Status RECRUITING

Memorial Sloan Kettering Cancer Center (Site: 840117)

New York, New York, United States

Site Status RECRUITING

Duke University (Site: 840110)

Durham, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

Mayo Clinic Florida

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania Health System

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

MD Anderson Cancer Center (Site: 840102)

Houston, Texas, United States

Site Status RECRUITING

University of Utah, Huntsman Cancer Center

Salt Lake City, Utah, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Institut de Recherches Internationales Servier Clinical Studies Department

Role: CONTACT

+33 1 55 72 43 66

Facility Contacts

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Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

Role: primary

ACC Clinical Trials Navigation

Role: primary

215-349-8245

Role: primary

Role: backup

References

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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

Reference Type BACKGROUND

Other Identifiers

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MK-3475-B39

Identifier Type: OTHER

Identifier Source: secondary_id

CL1-95032-005

Identifier Type: -

Identifier Source: org_study_id

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