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.
A phase-1, multi-center study in recurrent non-enhancing gliomas with IDH1 R132H mutation for patients who require surgery. The purpose of this study is to evaluate the suppression of 2-HG by comparing the concentration of 2-HG in resected tumors from IDH1 mutant glioma subjects following AG-120 or AG-881 treatment with the 2-HG concentration in untreated, control tumors. The safety, tolerability, PK/PD, and anti tumor activity data from the study in subjects with recurrent non-enhancing Grade 2/3 LGG with an IDH1 R132H mutation for whom surgical resection is indicated will identify the recommended dose of AG-120 and AG-881 for future studies in glioma.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
49
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.
United States, California
Los Angeles, California, United States
United States, California
San Francisco, California, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, New York
New York, New York, United States
2-HG concentration in surgically resected tumors
Time frame: Up to 4 weeks, on average
Safety and tolerability: incidence of adverse events and serious adverse events
Time frame: Up to 48 weeks, on average
Pharmacodynamics of AG-120 or AG-881 measured by 2-HG concentration in plasma.
Time frame: Up to 4 weeks, on average
Peak Plasma Concentration (Cmax) of AG-120 or AG-881
Time frame: Up to 4 weeks, on average
Time to maximum concentration (Tmax) of AG-120 or AG-881
Time frame: Up to 4 weeks, on average
Area Under the Curve (AUC) of AG-120 or AG-881
Time frame: Up to 4 weeks, on average
Elimination half-life of AG-120 or AG-881
Time frame: Up to 4 weeks, on average
Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria.
Time frame: Up to 48 weeks, on average
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United States, North Carolina
Durham, North Carolina, United States
United States, Texas
Dallas, Texas, United States