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

Servier Protocol Code: CL1-95032-005 Sponsor: Institut de Recherches Internationales Servier Clinicaltrials.gov Identifier: NCT05484622

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How to participate to the study?
If you think you are eligible for this study (see
eligibility criteria
below), you can identify the location closest to you and contact them directly. If you don’t find a location close to you, please contact Institut de Recherches Internationales Servier (I.R.I.S.)
Name: Institut de Recherches Internationales Servier, Département des études cliniques
Phone number: +33 1 55 72 60 00
The study has 17 locations

Study description

The study is needed to test a drug called vorasidenib in combination with a drug called pembrolizumab, in patients with a brain tumor called glioma. Glioma is a type of brain cancer that begins in ‘glial’ cells (the cells that surround and support nerve cells). It is a serious and rare disease with few effective treatment options.

The study includes patients whose tumours may have come back after surgery (called recurrent) or are getting worse (called progressive). Patients in this study have tumors with a specific gene change, called an IDH1 mutation.

In several types of cancer such as gliomas, an abnormal (mutated) form of a protein called isocitrate dehydrogenase (IDH) is present in the tumor cells due to changes called mutations. This leads to the overproduction of 2 hydroxyglutarate (2-HG), a substance that is normally present in cells at low levels. Too much 2-HG impairs normal cell functioning and may cause the cells to become tumor cells.

Vorasidenib blocks the activity of abnormal IDH1 proteins. Pembrolizumab is another medicine. It helps immune cells by blocking PD-1, a protein that cancer cells use to escape immune system. Studies have shown that combining vorasidenib with pembrolizumab may be a better option for these cancers.

The main goals of this study are:

  • To see if vorasidenib is safe and well-tolerated in combination with pembrolizumab in participants with recurrent or progressive glioma with an IDH1 mutation.
  • To find the recommended dose (the one that is both safe and effective for patients) of vorasidenib with pembrolizumab.
  • To check how effective is the combination of vorasidenib and pembrolizumab in by checking number of  CD3+ T-cells (a type of immune cell) that enter tumors after treatment , compared to tumors without any treatment before surgery.
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
Conditions
Astrocytoma Oligodendroglioma
Interventions / Treatments
  • Vorasidenib
  • Pembrolizumab
Other study id numbers
  • CL1-95032-005

Eligibility Criteria

Eligible age for the study

18 years and older (Adult, Older Adult)

Sexes

Male/Female

Accepts Healthy Volunteers

No

To take part in the study, participants have to:

  • Be adults aged 18 or older.
  • Have confirmed recurrent or progressive glioma with a documented IDH1 mutation.
  • Have previously received treatment with chemotherapy (treatment with medications), radiation, or both.

Participants cannot take part in the study if they:

  • Had received treatment with anticancer medicines in the month before starting the study drug.
  • Had received treatment with radiation in the year before starting the study drug.
  • Have received two or more courses of radiation treatment.

How is the study designed?

Allocation
Randomized
Interventional study model
Sequential
Participant Group / Arm
Experimental: Safety Lead-In Phase: Vorasidenib + Pembrolizumab

Participants take vorasidenib orally once a day, along with pembrolizumab given through intravenous infusion (injection given slowly) into their vein at a dose of 200 mg once every three weeks. This occurs in 21-day cycles and continues until the disease gets worse, there are too severe side effects, or other reasons to stop the treatment arise.

Intervention / Treatment
Drug: Vorasidenib

A tablet taken orally.

Drug: Pembrolizumab

Injected slowly into a vein (IV).

Participant Group / Arm
Experimental: Randomized Perioperative Phase: Vorasidenib + Pembrolizumab

Participants take the recommended dose of vorasidenib (determined in the earlier phase) orally once a day from Day 1 to Day 28. They also receive pembrolizumab through an intrevenous infusion at a dose of 200 mg once every three weeks on Days 1 and 22 of a 28-day cycle before surgery.

Intervention / Treatment
Drug: Vorasidenib

A tablet taken orally.

Drug: Pembrolizumab

Injected slowly into a vein (IV).

Participant Group / Arm
Experimental: Randomized Perioperative Phase: Vorasidenib Only

Participants take vorasidenib orally once a day from Day 1 to Day 28 of a 28-day cycle before surgery.

Intervention / Treatment
Drug: Vorasidenib

A tablet taken orally.

Participant Group / Arm
No Intervention: Randomized Perioperative Phase: Untreated Control Group

Participants do not receive any treatment before surgery.

Intervention / Treatment

Keywords

Provided by Servier
Vorasidenib AG-881 Pembrolizumab IDH-1 Astrocytoma Oligodendroglioma Enchancing Non-enchancing
Additional Relevant MeSH Terms Glioma
Astrocytoma Oligodendroglioma