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AstrocytomaPhase 1NCT05484622

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

A Phase 1 study testing Vorasidenib and Pembrolizumab in people with Astrocytoma and Oligodendroglioma, run by Institut de Recherches Internationales Servier at 17 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive isocitrate dehydrogenase-1 (IDH-1) mutant Glioma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Astrocytoma, Oligodendroglioma
What is being tested?
Vorasidenib and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
17 sitesUnited States
Study dates
20 Jan 2023to 30 Aug 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • 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.
Show all 9Show fewer
  • 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).

Who cannot join

  • 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.
  • Note: Other inclusion and exclusion criteria may apply.

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • University of Michigan

    Ann Arbor, Michigan, 48109

  • University of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35249

  • Massachusetts General Hospital (Site: 840104)

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute (Site: 840139)

    Boston, Massachusetts, 02215

  • Northwestern University (Site: 840123)

    Chicago, Illinois, 60045

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Mayo Clinic Florida

    Cleveland, Ohio, 44195

  • Duke University (Site: 840110)

    Durham, North Carolina, 27705

  • MD Anderson Cancer Center (Site: 840102)

    Houston, Texas, 77030

  • University of California, Los Angeles (Site: 840113)

    Los Angeles, California, 90095

  • University of Miami (Site: 840129)

    Miami, Florida, 33136

  • Memorial Sloan Kettering Cancer Center (Site: 840117)

    New York, New York, 10017

  • University of Pennsylvania Health System

    Philadelphia, Pennsylvania, 19104

  • University of Utah, Huntsman Cancer Center

    Salt Lake City, Utah, 84112

  • University of California, San Francisco (Site: 840149)

    San Francisco, California, 94013

Other trials in United States

About this study

Official title: 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

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

Read the detailed description

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.

Being tested
Vorasidenib, Pembrolizumab
Keywords
Vorasidenib, AG-881, Pembrolizumab, IDH-1, Astrocytoma, Oligodendroglioma, Enchancing, Non-enchancing
Medical subject headings
Astrocytoma, Oligodendroglioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VorasidenibDrug

    Also called S095032, AG-881

    Administered orally as tablets.

  • PembrolizumabDrug

    Also called MK-3475, KEYTRUDA®, KEYNOTE-B39, MK-3475-B39

    Administered as IV infusion.

Study groups in NCT05484622
Study groupRoleWhat they receive
Safety Lead-In Phase: Vorasidenib + PembrolizumabExperimentalParticipants 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.
Receives: Drug: Vorasidenib; Drug: Pembrolizumab
Randomized Perioperative Phase: Vorasidenib + PembrolizumabExperimentalParticipants 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.
Receives: Drug: Vorasidenib; Drug: Pembrolizumab
Randomized Perioperative Phase: Vorasidenib OnlyExperimentalParticipants will receive vorasidenib orally, QD from Day 1 to 28 of a 28-day cycle prior to surgery.
Receives: Drug: Vorasidenib
Randomized Perioperative Phase: Untreated Control GroupNo interventionParticipants will not receive any treatment prior to surgery.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety Lead-in Phase: Percentage of Participants With Dose-limiting Toxicities (DLTs)

    Measured: First 21 days of dosing (Cycle 1) in safety lead-in phase

  2. Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Measured: approximately up to 19 months

  3. 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.

    Measured: approximately 2 months

Secondary outcomes (7)

  1. Overall Survival (OS)

    Overall survival is defined as the time from the date of first dose (in Safety Lead-in) or first postoperative dose (in randomized perioperative phase) to the date of death due to any cause.

    Measured: Up to approximately 55 months

  2. AUC: Area Under the Plasma Concentration-Time Curve of Vorasidenib

    Measured: approximately 16 months

  3. Cmax: Maximum Observed Plasma Concentration of Vorasidenib

    Measured: approximately 16 months

  4. Concentration of 2-hydroxygluarate (2-HG) in Surgically Resected Tumors

    Measured: approximately 2 months

  5. Concentration of Vorasidenib in Surgically Resected Tumors

    Measured: approximately 2 months

  6. Clinical Activity Associated With Vorasidenib in Combination With Pembrolizumab According to Modified Response Assessment in Neuro-oncology (mRANO) Criteria

    Measured: Up to approximately 16 months

  7. Time to response

    Defined as the time from the date of first dose (in Safety Lead-In) or the date of first postoperative dose (in randomized perioperative phase) to the date of first documented objective response as assessed by the Investigator per Modified Response Assessment in Neuro-oncology (mRANO) criteria.

    Measured: Up to approximately 55 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Aug 2022
  2. Study start20 Jan 2023
  3. Primary completion12 Feb 2026
  4. Study completion30 Aug 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
Sequential design for safety lead-in and randomized perioperative phases, parallel design within randomized perioperative phase.
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05484622
Sponsor's protocol ID
CL1-95032-005
Other IDs
MK-3475-B39
Status last verified
Mar 2026
First submitted
21 Jul 2022
Last updated
12 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vorasidenib and Pembrolizumab in people with Astrocytoma and Oligodendroglioma, run by Institut de Recherches Internationales Servier at 17 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 12 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety Lead-in Phase: Percentage of Participants With Dose-limiting Toxicities (DLTs) (time frame: First 21 days of dosing (Cycle 1) in safety lead-in phase). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05484622, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Mar 2026.

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