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Combination of Vorasidenib and Pembrolizumab for 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

Phase 1 Interventional Servier · NCT05484622

This study is testing if a new combination of two drugs, vorasidenib and pembrolizumab, can help people with recurrent or progressive IDH-1 mutant glioma feel better and improve their treatment outcomes before surgery.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment72 (estimated)
Ages18 Years and up
SexAll
SponsorServier Industry-sponsored
Drugs / interventionsbevacizumab, chemotherapy, radiation, pembrolizumab
Locations16 sites (Birmingham, Alabama and 15 other locations)
Trial IDNCT05484622 on ClinicalTrials.gov

What this trial studies

This study evaluates the safety and efficacy of vorasidenib in combination with pembrolizumab in patients with recurrent or progressive IDH-1 mutant glioma. It consists of two phases: a Safety Lead-In phase to determine the recommended combination dose of vorasidenib, followed by a randomized perioperative phase to assess lymphocyte infiltration in tumors after pre-surgical treatment. Participants will be randomized to receive either the combination treatment, vorasidenib alone, or no treatment before surgery. Post-surgery, participants may continue receiving the combination treatment in 21-day cycles until disease progression or unacceptable toxicity occurs.

Who should consider this trial

Good fit: Ideal candidates include individuals with Grade 2 or Grade 3 glioma who have a documented IDH1-R132H gene mutation and meet specific eligibility criteria.

Not a fit: Patients without the IDH1-R132H mutation or those with non-measurable disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could improve outcomes for patients with recurrent or progressive IDH-1 mutant glioma.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific combination is novel.

Eligibility criteria

Show full inclusion / exclusion criteria 
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.

Note: Other inclusion and exclusion criteria may apply.

Where this trial is running

Birmingham, Alabama and 15 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions AstrocytomaOligodendrogliomaVorasidenibAG-881PembrolizumabIDH-1EnchancingNon-enchancing
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.