A Phase 1 First-in-Human Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 595 in Subjects With Recurrent Malignant Glioma Expressing Mutant Epidermal Growth Factor Receptor Variant III (EGFRvIII)
- 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.
- 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
- 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.
- Treated previously with bevacizumab or anti-angiogenic therapy for the dose expansion
(Part 2) only.