RECRUITING

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

Conditions

Astrocytoma Oligodendroglioma Vorasidenib AG-881 Pembrolizumab IDH-1 Enchancing Non-enchancing

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Vorasidenib in combination with pembrolizumab in participants with recurrent or progressive isocitrate dehydrogenase-1 (IDH-1) mutant Glioma.

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

Quick Facts

Study Start:2023-01-20

Study Completion:2027-08-30

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05484622

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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).	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.

Inclusion Criteria

Exclusion 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).

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.

Contacts and Locations

Study Contact

Institut de Recherches Internationales Servier Clinical Studies Department

CONTACT

+33 1 55 72 43 66

scientificinformation@servier.com

Study Locations (Sites)

University of Alabama at Birmingham

Birmingham, Alabama, 35249

United States

University of California, Los Angeles (Site: 840113)

Los Angeles, California, 90095

United States

University of California, San Francisco (Site: 840149)

San Francisco, California, 94013

United States

University of Colorado

Aurora, Colorado, 80045

United States

University of Miami (Site: 840129)

Miami, Florida, 33136

United States

Northwestern University (Site: 840123)

Chicago, Illinois, 60045

United States

Johns Hopkins University

Baltimore, Maryland, 21287

United States

Massachusetts General Hospital (Site: 840104)

Boston, Massachusetts, 02114

United States

Dana-Farber Cancer Institute (Site: 840139)

Boston, Massachusetts, 02215

United States

University of Michigan

Ann Arbor, Michigan, 48109

United States

Memorial Sloan Kettering Cancer Center (Site: 840117)

New York, New York, 10017

United States

Duke University (Site: 840110)

Durham, North Carolina, 27705

United States

Cleveland Clinic

Cleveland, Ohio, 44195

United States

Mayo Clinic Florida

Cleveland, Ohio, 44195

United States

MD Anderson Cancer Center (Site: 840102)

Houston, Texas, 77030

United States

University of Utah, Huntsman Cancer Center

Salt Lake City, Utah, 84112

United States

Collaborators and Investigators

Sponsor: Institut de Recherches Internationales Servier

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-01-20

Study Completion Date2027-08-30

Study Record Updates

Study Start Date2023-01-20

Study Completion Date2027-08-30

Terms related to this study

Keywords Provided by Researchers

Vorasidenib
AG-881
Pembrolizumab
IDH-1
Astrocytoma
Oligodendroglioma
Enchancing
Non-enchancing

Additional Relevant MeSH Terms

Astrocytoma
Oligodendroglioma