Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive IDH-1 Mutant Glioma
Purpose
Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive enhancing isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.
Condition
- Astrocytoma
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Have Karnofsky Performance Status (KPS) of ≥ 70%. 2. Have expected survival of ≥ 3 months. 3. Have histologically confirmed Grade 2 or Grade 3 astrocytoma (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
- 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.
Study Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- Sequential design for safety lead-in and randomized perioperative phases, parallel design within randomized perioperative phase.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental 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. |
|
|
Experimental 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. |
|
|
Experimental Randomized Perioperative Phase: Vorasidenib Only |
Participants will receive vorasidenib orally, QD from Day 1 to 28 of a 28-day cycle prior to surgery. |
|
|
No Intervention Randomized Perioperative Phase: Untreated Control Group |
Participants will not receive any treatment prior to surgery. |
|
Recruiting Locations
University of Alabama at Birmingham
Birmingham, Alabama 35249
Birmingham, Alabama 35249
More Details
- Status
- Recruiting
- Sponsor
- Institut de Recherches Internationales Servier
Study Contact
Institut de Recherches Internationales Servier Clinical Studies Department+33 1 55 72 43 66
scientificinformation@servier.com
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.