Phase II Study of Rindopepimut (CDX-110) in Patients With Glioblastoma Multiforme (ACT III)

• PFS at 6 months in Phase II
• Median OS in Phase III

• Safety and tolerability characterized by adverse events (term, grade, frequency). [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Safety and tolerability characterized by physical examinations. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Safety and tolerability characterized by hematologic and metabolic panel (including CBC with differential, electrolytes, BUN, Cr, liver associated enzymes). [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Safety and tolerability characterized by urinalysis. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Safety and tolerability characterized by vital signs. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
• Immune response; T-cell response to vaccine. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Immune response; antibody response to vaccine. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Immune response; HLA typing. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
• Overall survival. [ Time Frame: indeterminate ] [ Designated as safety issue: No ]

• Safety
• Immune Response rate

This study is designed to evaluate the clinical activity of CDX-110 vaccination when given with standard of care treatment (maintenance temozolomide therapy). Study treatment will be given until disease progression and patients will be followed for long-term survival information. Efficacy will be measured by the progression-free survival status at 5.5 months from the date of first dose.

• Drug: CDX-110 with GM-CSF
  Three biweekly intradermal injections over four weeks followed by monthly injections until tumor progression. Each dose will be 0.8 mL containing approximately 500 mcg CDX-110 and 150 mcg GM CSF
  Other Name: CDX-110 with sargramostim (GM-CSF) (Leukine®)
• Drug: temozolomide
  Maintenance temozolomide will begin after completion of the three initial injections of CDX-110 plus GM-CSF. 150 to 200 mg/m2 for 5 days during each 28-day cycle for a minimum of six cycles or a maximum of 12 cycles , intolerance or progression.
  Other Name: Temodar

Inclusion Criteria:

• Newly diagnosed de novo GBM with documented EGFRvIII expression in tumor tissue.
• Gross total resection followed by conventional chemoradiation therapy without progression of disease.

Exclusion Criteria:

• Presence of diffuse leptomeningeal disease or gliomatosis cerebri.
• Systemic corticosteroid therapy > 2 mg of dexamethasone or equivalent (as defined by the investigator) per day at study enrollment.
• Patients who have undergone stereotactic radiosurgery prior to or following surgical resection, or the placement of Gliadel® Wafers.
• Known allergy or hypersensitivity to KLH, GM-CSF or yeast derived products, or a history of anaphylactic reactions to shellfish proteins.