A Phase 2 Study of PLX3397 in Patients With Recurrent Glioblastoma

Inclusion Criteria:

- Male or female patients ≥18 years old with a life expectancy of at least 8 weeks

- Radiographically proven recurrent (≥ first relapse), intracranial GBM

- For all patients, availability of at least 10 unstained slides (or archival tumor
block sufficient to generate at least 10 unstained slides) from any previous GBM
surgery

- Previous treatment with external beam radiation and temozolomide chemotherapy

- Before the first dose of PLX3397,adequate recovery from toxicity of prior therapy as
follows:

>28 days for cytotoxic therapy >42 days for nitrosoureas >28 days for bevacizumab >7 days
for non cytotoxic therapy such as interferon, tamoxifen, thalidomide, cis-retinoic acid, or
erlotinib

- Women of child-bearing potential must have a negative pregnancy test within 7 days of
initiation of dosing and must agree to use an acceptable method of birth control while
on study drug and for 3 months after the last dose. Women of non-childbearing
potential may be included if they are either surgically sterile or have been
postmenopausal for ≥1 year. Men of child-bearing potential must also agree to use an
acceptable method of birth control while on study drug.

- Karnofsky performance status of ≥60

- Adequate hematologic, hepatic, and renal function (absolute neutrophil count ≥1.0 x
109/L, Hgb >9 g/dL, platelet count ≥50 x 109/L, AST/ALT ≤2.5x ULN, creatinine ≤1.5x
ULN)

- Willing and able to provide written informed consent prior to any study related
procedures and to comply with all study requirements

Exclusion Criteria:

- Investigational drug use within 28 days of the first dose of PLX3397

- GBM progression within 3 months of previous radiation by RANO criteria

- History of Grade 2 (CTCAE v4) or greater acute intracranial hemorrhage

- Previous failure of bevacizumab or other VEGF therapy except in a first line setting

- History of malignant glioma with co-deletion of 1p/19q

- A concurrent active cancer that requires non-surgical therapy (e.g. chemotherapy,
radiation, adjuvant therapy). Prior history of other cancer is allowed, as long as
there was no active disease within the prior 3 years.

- Refractory nausea and vomiting, malabsorption, biliary shunt, or significant bowel
resection that would preclude adequate absorption

- Patients with serious illnesses, uncontrolled infection, medical conditions, or other
medical history including abnormal laboratory results, which in the investigator's
opinion would be likely to interfere with a patient's participation in the study, or
with the interpretation of the results

- Women of child-bearing potential who are pregnant or breast feeding

- QTc ≥450 msec at Screening