Study of AG-120 and AG-881 in Subjects With Low Grade Glioma
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Detailed Description
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: AG-120 AG-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 . |
Drug: AG-120
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.
|
| Experimental: AG-881 AG-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. |
Drug: AG881
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.
|
| No Intervention: No Treatment Pre-Surgery Subjects will not receive treatment prior to surgery. Following surgery, subjects will have the option to receive treatment with AG-120 or AG-881. |
Outcome Measures
Primary Outcome Measures
- 2-HG concentration in surgically resected tumors [Up to 4 weeks, on average]
Secondary Outcome Measures
- 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]
- Elimination half-life of AG-120 or AG-881 [Up to 4 weeks, on average]
- Clinical activity associated with AG-120 or AG-881 according to modified RANO_LGG criteria. [Up to 48 weeks, on average]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Be ≥18 years of age.
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Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG (oligodendroglioma or astrocytoma according to World Health Organization 2016 classification).
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Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX mutation status by local testing.
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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.
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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).
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Have KPS of ≥60%
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Have expected survival of ≥12 months.
Exclusion Criteria:
-
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.
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Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior biopsy or surgery is allowed.)
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Have received any prior treatment with an IDH inhibitor.
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Have received any prior treatment with bevacizumab (Avastin).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | United States, California | Los Angeles | California | United States | 90024 |
| 2 | United States, California | San Francisco | California | United States | 94143 |
| 3 | United States, Massachusetts | Boston | Massachusetts | United States | 02215 |
| 4 | United States, New York | New York | New York | United States | 10065 |
| 5 | United States, North Carolina | Durham | North Carolina | United States | 27710 |
| 6 | United States, Texas | Dallas | Texas | United States | 75390 |
Sponsors and Collaborators
- Institut de Recherches Internationales Servier
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AG120-881-C-001