Study of AG-120 and AG-881 in Subjects With Low Grade Glioma
A Phase 1, Multicenter, Randomized, Controlled, Open-Label, Perioperative Study of AG-120 and AG-881 in Subjects With Recurrent, Non-Enhancing, IDH1 Mutant, Low Grade Glioma
1 other identifier
interventional
49
1 country
6
Brief Summary
Study to evaluate the suppression of 2-HG (2-hydroxyglutarate) in IDH-1 mutant gliomas in resected tumor tissue following pre-surgical treatment with AG-120 or AG-881.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Mar 2018
Longer than P75 for phase_1
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 7, 2017
CompletedFirst Posted
Study publicly available on registry
November 17, 2017
CompletedStudy Start
First participant enrolled
March 20, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 2, 2019
CompletedStudy Completion
Last participant's last visit for all outcomes
March 28, 2025
CompletedFebruary 17, 2026
February 1, 2026
1.4 years
November 7, 2017
February 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
2-HG concentration in surgically resected tumors
Up to 4 weeks, on average
Secondary Outcomes (7)
Safety and tolerability: incidence of adverse events and serious adverse events
Up to 48 weeks, on average
Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.
Up to 4 weeks, on average
Peak Plasma Concentration (Cmax) of AG-120 or AG-881
Up to 4 weeks, on average
Time to maximum concentration (Tmax) of AG-120 or AG-881
Up to 4 weeks, on average
Area Under the Curve (AUC) of AG-120 or AG-881
Up to 4 weeks, on average
- +2 more secondary outcomes
Study Arms (3)
AG-120
EXPERIMENTALAG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 .
AG-881
EXPERIMENTALAG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-881.
No Treatment Pre-Surgery
NO INTERVENTIONSubjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881.
Interventions
Prior to surgery subjects will receive AG-120 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.
Prior to surgery subjects will receive AG-881 administered continuously as a single agent dosed orally on Days 1 to 28 of a 28-day cycle. Subjects without residual disease following surgery will have the option to receive treatment for up to a year, until disease progression or unacceptable toxicity, whichever occurs first. Subjects with residual disease following surgery will have the option to receive treatment, until disease progression or unacceptable toxicity.
Eligibility Criteria
You may qualify if:
- Be ≥18 years of age.
- Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification).
- Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
- Have central confirmation of primarily non-enhancing disease by MRI with less than or equal to 5 mm slice thickness and up to 1 mm interslice gap on either 2D T2 weighted image, 3D T2 weighted image, or FLAIR, with at least 1 non-enhancing tumor measuring 1×1×1 cm.
- Be candidates for clinical resection but for whom surgery is not urgently indicated (eg, for whom surgery within the next 2-4 months is appropriate).
- Have KPS of ≥60%
- Have expected survival of ≥12 months.
You may not qualify if:
- Have received prior systemic anti-cancer therapy within 1 month of the first dose of AG-120 or AG-881 or have received an investigational agent \<14 days prior to their first dose of AG-120 or AG-881. In addition, the first dose of AG-120 or AG-881 should not occur before a period of ≥5 half-lives of the investigational agent has elapsed.
- Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior biopsy or surgery is allowed.)
- Have received any prior treatment with an IDH inhibitor.
- Have received any prior treatment with bevacizumab (Avastin).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
United States, California
Los Angeles, California, 90024, United States
United States, California
San Francisco, California, 94143, United States
United States, Massachusetts
Boston, Massachusetts, 02215, United States
United States, New York
New York, New York, 10065, United States
United States, North Carolina
Durham, North Carolina, 27710, United States
United States, Texas
Dallas, Texas, 75390, United States
Related Publications (1)
Mellinghoff IK, Lu M, Wen PY, Taylor JW, Maher EA, Arrillaga-Romany I, Peters KB, Ellingson BM, Rosenblum MK, Chun S, Le K, Tassinari A, Choe S, Toubouti Y, Schoenfeld S, Pandya SS, Hassan I, Steelman L, Clarke JL, Cloughesy TF. Vorasidenib and ivosidenib in IDH1-mutant low-grade glioma: a randomized, perioperative phase 1 trial. Nat Med. 2023 Mar;29(3):615-622. doi: 10.1038/s41591-022-02141-2. Epub 2023 Feb 23.
PMID: 36823302BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 7, 2017
First Posted
November 17, 2017
Study Start
March 20, 2018
Primary Completion
August 2, 2019
Study Completion
March 28, 2025
Last Updated
February 17, 2026
Record last verified: 2026-02
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- After Marketing Authorisation in EEA or US if the study is used for the approval.
- Access Criteria
- Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data. Access can be requested for all interventional clinical studies: * used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US). * where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope. In addition, access can be requested for all interventional clinical studies in patients: * sponsored by Servier * with a first patient enrolled as of 1 January 2004 onwards * for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.