Study of AG-120 and AG-881 in Subjects With Low Grade Glioma

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.

Inclusion Criteria:

1. Be ≥18 years of age.

2. Have histologically or cytologically confirmed recurrent Grade 2 or 3 LGG
(oligodendroglioma or astrocytoma according to World Health Organization 2016
classification).

3. Have documented IDH1 R132H gene mutation by local testing and known 1p19q or ATRX
mutation status by local testing.

4. 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.

5. 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).

6. Have KPS of ≥60%

7. Have expected survival of ≥12 months.

Exclusion Criteria:

1. 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.

2. Have had radiation within 6 months of the first dose of AG-120 or AG-881. (Note: Prior
biopsy or surgery is allowed.)

3. Have received any prior treatment with an IDH inhibitor.

4. Have received any prior treatment with bevacizumab (Avastin).