Trial Title:
Study of Vorasidenib and Pembrolizumab Combination in Recurrent or Progressive Enhancing IDH-1 Mutant Glioma
NCT ID:
NCT05484622
Condition:
Astrocytoma
Conditions: Official terms:
Astrocytoma
Pembrolizumab
Conditions: Keywords:
Vorasidenib
AG-881
Pembrolizumab
IDH-1
Astrocytoma
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
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)
Intervention:
Intervention type:
Drug
Intervention name:
Vorasidenib
Description:
Administered orally as tablets.
Arm group label:
Randomized Perioperative Phase: Vorasidenib + Pembrolizumab
Arm group label:
Randomized Perioperative Phase: Vorasidenib Only
Arm group label:
Safety Lead-In Phase: Vorasidenib + Pembrolizumab
Other name:
S095032
Other name:
AG-881
Intervention type:
Drug
Intervention name:
Pembrolizumab
Description:
Administered as IV infusion.
Arm group label:
Randomized Perioperative Phase: Vorasidenib + Pembrolizumab
Arm group label:
Safety Lead-In Phase: Vorasidenib + Pembrolizumab
Other name:
MK-3475
Other name:
KEYTRUDA®
Other name:
KEYNOTE-B39
Other name:
MK-3475-B39
Summary:
Vorasidenib in combination with pembrolizumab in participants with recurrent or
progressive enhancing isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.
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.
Criteria for eligibility:
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 astrocytoma (per the 2016 or 2021
World Health Organization [WHO] Classification of Tumors of the central nervous
system)
4. 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.
5. Have measurable, magnetic resonance imaging (MRI)-evaluable, unequivocal contrast
enhancing disease as determined by institution 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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
University of California, Los Angeles (Site: 840113)
Address:
City:
Los Angeles
Zip:
90095
Country:
United States
Status:
Recruiting
Contact:
Email:
shwiles@mednet.ucla.edu
Facility:
Name:
University of California, San Francisco (Site: 840149)
Address:
City:
San Francisco
Zip:
94013
Country:
United States
Status:
Recruiting
Contact:
Email:
NeuroOncNewPatientCoord@ucsf.edu
Facility:
Name:
University of Colorado
Address:
City:
Aurora
Zip:
80045
Country:
United States
Status:
Recruiting
Facility:
Name:
University of Miami (Site: 840129)
Address:
City:
Miami
Zip:
33136
Country:
United States
Status:
Recruiting
Contact:
Email:
yxp303@med.miami.edu
Facility:
Name:
Northwestern University (Site: 840123)
Address:
City:
Chicago
Zip:
60045
Country:
United States
Status:
Recruiting
Contact:
Email:
cancertrials@northwestern.edu
Facility:
Name:
Johns Hopkins University
Address:
City:
Baltimore
Zip:
21287
Country:
United States
Status:
Recruiting
Facility:
Name:
Massachusetts General Hospital (Site: 840104)
Address:
City:
Boston
Zip:
02114
Country:
United States
Status:
Recruiting
Contact:
Email:
lmhibyan@mgb.org
Facility:
Name:
Dana-Farber Cancer Institute (Site: 840139)
Address:
City:
Boston
Zip:
02215
Country:
United States
Status:
Recruiting
Contact:
Email:
Patrick_wen@dfci.harvard.edu
Facility:
Name:
University of Michigan
Address:
City:
Ann Arbor
Zip:
48109
Country:
United States
Status:
Recruiting
Facility:
Name:
Memorial Sloan Kettering Cancer Center (Site: 840117)
Address:
City:
New York
Zip:
10017
Country:
United States
Status:
Recruiting
Contact:
Email:
KeithN@mskcc.org
Facility:
Name:
Duke University (Site: 840110)
Address:
City:
Durham
Zip:
27705
Country:
United States
Status:
Recruiting
Contact:
Email:
dukebrain1@dm.duke.edu
Facility:
Name:
Cleveland Clinic
Address:
City:
Cleveland
Zip:
44195
Country:
United States
Status:
Recruiting
Facility:
Name:
MD Anderson Cancer Center (Site: 840102)
Address:
City:
Houston
Zip:
77030
Country:
United States
Status:
Recruiting
Contact:
Email:
Egachimova@mdanderson.org
Contact backup:
Email:
hsal@mdanderson.org
Facility:
Name:
University of Utah, Huntsman Cancer Center
Address:
City:
Salt Lake City
Zip:
84112
Country:
United States
Status:
Recruiting
Start date:
January 20, 2023
Completion date:
August 30, 2027
Lead sponsor:
Agency:
Institut de Recherches Internationales Servier
Agency class:
Other
Collaborator:
Agency:
Merck Sharp & Dohme LLC
Agency class:
Industry
Source:
Servier
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05484622
