Celldex Therapeutics has launched a phase III trial of rindopepimut in patients with surgically resected epidermal growth factor variant III (EGFRvIII)-positive glioblastoma, the "ACT IV Study." US investigators have started screening patients for inclusion in the trial that is expected to enroll up to 440 patients internationally to recruit 374 patients with Gross Total Resection (GTR) for the primary analysis. Rindopepimut is a therapeutic cancer vaccine candidate that targets the tumor-specific oncogene EGFRvIII, which confers an enhanced capacity for unregulated tumor growth and which is present in many cancer cell types, but not present at significant levels in normal cells.
The ACT IV study is a randomized, double-blind, controlled study of rindopepimut plus GM-CSF added to standard of care temozolomide in patients with newly diagnosed, surgically resected, EGFRvIII-positive glioblastoma. Patients will be randomized after the completion of surgery and standard chemoradiation. The treatment regime includes a vaccine priming phase post-radiation followed by an adjuvant temozolomide phase and a vaccine maintenance therapy phase. Patients will be treated until disease progression or intolerance to therapy. The primary objective of the study is to determine whether rindopepimut plus GM-CSF improves the overall survival of patients with newly diagnosed EGFRvIII positive glioblastoma after GTR when compared to treatment with the current standard of care, temozolomide. A total of approximately 440 patients will be enrolled at over 150 centers worldwide to recruit 374 patients with GTR to be included in the primary analysis. Secondary endpoints include: progression free survival; safety and tolerability of rindopepimut and GM-CSF in combination with temozolomide; neurologic status and quality of life. Patients will be stratified based upon geographic region, RPA class prognostic factors and MGMT methylation status.