A Phase 2 Study of MEDI-575 in Adult Subjects With Recurrent Glioblastoma Multiforme

Inclusion Criteria:

- Written informed consent and HIPAA authorization (applies to covered entities in the
USA only) obtained from the subject/legal representative prior to performing any
protocol-related procedures, including screening evaluations

- Age ≥18 years old at the time of screening

- Histologically confirmed diagnosis of World Health Organization Grade IV malignant
glioma (glioblastoma or gliosarcoma)

- Previous first line treatment with radiotherapy and temozolomide (treatment prior to
radiation and temozolomide permitted, [ie, Gliadel])

- Documented first recurrence of GBM by diagnostic biopsy or by contrast-enhanced
magnetic resonance imaging (MRI) as per Updated Response Assessment Criteria of High
Grade Gliomas- Neuro-Oncology Working Group (Wen et al, 2010)

- Life expectancy ≥ 12 weeks

- Adequate hematologic and organ function

- Negative serum pregnancy test (women only)

- Two methods of birth control for female participants of child-bearing potential or
male participants with their female partners of child-bearing potential

Exclusion Criteria:

- Treatment with any chemotherapy, radiotherapy, immunotherapy, biologic, hormonal
therapy or investigational agent 30 days prior to study entry

- Concurrent enrollment in another clinical study involving an investigational agent

- Employees of the clinical study site or any other individuals involved with the
conduct of the study, or immediate family members of such individuals

- Previous mAb treatment specifically directed against PDGF or PDGF receptors

- Previous bevacizumab or other VEGF and anti-angiogenic treatment

- More than 1 recurrence of GBM

- Any surgery (not including minor diagnostic procedures) within 2 weeks prior to
baseline disease assessments; or not fully recovered from any side effects of
previous procedures

- History of serious allergy or reaction to any component of the MEDI-575 formulation

- New York Heart Association ≥ Grade 2 congestive heart failure within 6 months prior
to study entry

- Uncontrolled or significant cardiovascular disease

- History of other invasive malignancy within 5 years prior to study entry except for
cervical carcinoma in situ (CIS), non-melanomatous carcinoma of the skin or ductal
carcinoma in situ (DCIS) of the breast that have been surgically cured

- History of active human immunodeficiency virus or active hepatitis B or C viral
infection will be excluded to eliminate the risk of increased AEs due to immune
compromise.

- Systemic immunosuppressive therapy.

- Subjects taking corticosteroids must be on a stable dose for 7 days prior to
initiation of treatment with MEDI-575 16) Presence of extracranial metastatic or
leptomeningeal disease