Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
72
Administered orally as tablets.
Administered as IV infusion.
University of Alabama at Birmingham
Birmingham, Alabama, United States
RECRUITINGSafety 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
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: approximately up to 19 months
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.
Time frame: approximately 2 months
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.
Time frame: Up to approximately 55 months
AUC: Area Under the Plasma Concentration-Time Curve of Vorasidenib
Time frame: approximately 16 months
Cmax: Maximum Observed Plasma Concentration of Vorasidenib
Time frame: approximately 16 months
Concentration of 2-hydroxygluarate (2-HG) in Surgically Resected Tumors
Time frame: approximately 2 months
Concentration of Vorasidenib in Surgically Resected Tumors
Time frame: approximately 2 months
Clinical Activity Associated With Vorasidenib in Combination With Pembrolizumab According to Modified Response Assessment in Neuro-oncology (mRANO) Criteria
Institut de Recherches Internationales Servier Clinical Studies Department
CONTACT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
University of California, Los Angeles (Site: 840113)
Los Angeles, California, United States
RECRUITINGUniversity of California, San Francisco (Site: 840149)
San Francisco, California, United States
RECRUITINGUniversity of Colorado
Aurora, Colorado, United States
RECRUITINGUniversity of Miami (Site: 840129)
Miami, Florida, United States
RECRUITINGNorthwestern University (Site: 840123)
Chicago, Illinois, United States
RECRUITINGJohns Hopkins University
Baltimore, Maryland, United States
RECRUITINGMassachusetts General Hospital (Site: 840104)
Boston, Massachusetts, United States
RECRUITINGDana-Farber Cancer Institute (Site: 840139)
Boston, Massachusetts, United States
RECRUITINGUniversity of Michigan
Ann Arbor, Michigan, United States
RECRUITING...and 7 more locations
Time frame: Up to approximately 16 months
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.
Time frame: Up to approximately 55 months