AMG 595 First-in-Human in Recurrent Gliomas

Inclusion Criteria:

* Karnofsky performance score \> or = 70%
* Must have pathologically documented, and definitively diagnosed recurrent WHO Grade IV advanced malignant glioblastoma multiforme (Part 1 and Part 2) and/or WHO Grade III anaplastic astrocytoma (Part 1 only).
* GBM and/or AA tumors expressing EGFRvIII as assessed on archived tissue by IHC staining of sections containing a minimum of 100 evaluable tumor cells.
* Archived tumor tissue from the initial diagnosis or subsequent relapse(s) of Grade IV advanced malignant glioblastoma multiforme or Grade III anaplastic astrocytoma available for submission to central review.
* Subjects with recurrent disease (confirmed by MRI and evaluable by Macdonald criteria) at the time of first or second recurrence or progression following initial definitive therapy(s)
* QTcF ≤ 470 msec
* Hematological function, as follows: Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, Platelet count ≥ 100 x 10\^9/L, Hemoglobin \> 9 g/dL
* Renal function, as follows: Estimated glomerular filtration rate using the Modified Diet in Renal Disease (MDRD) equation \> 45 mL/min/1.73m\^2, Urinary protein quantitative value of \< 30 mg/dL in urinalysis or ≤ 1+ on dipstick, unless quantitative protein is \< 500 mg in a 24 hr urine sample

Exclusion Criteria:

* History of central nervous system bleeding as defined by stroke or intraocular bleed (including embolic stroke) within 6 months before enrollment.
* Evidence of acute intracranial / intratumoral hemorrhage, except for subjects with stable grade 1 hemorrhage.
* Peripheral sensory neuropathy \> Grade 2.
* Clinically significant ECG changes which obscure the ability to assess the PR, QT, and QRS interval; congenital long QT syndrome.
* Recent infection requiring intravenous anti-infective treatment that was completed ≤ 14 days before enrollment.
* Received radiation therapy within 12 weeks before enrollment or has not recovered from the toxic effects of such therapy.
* For Part 1 (dose escalation): Treatment with bevacizumab or antiangiogenic therapy within 4 weeks before enrollment, or for Part 2 (dose expansion): any prior treatment with bevacizumab or antiangiogenic therapy.