IMCT-04TOCA 5: PHASE 2/3 RANDOMIZED, OPEN-LABEL STUDY OF TOCA 511 WITH TOCA FC VERSUS STANDARD OF CARE IN PATIENTS UNDERGOING PLANNED RESECTION FOR RECURRENT HIGH GRADE GLIOMA (NCT02414165)

Abstract

Recurrent glioblastoma and anaplastic astrocytoma have a dismal prognosis and a high unmet need for effective therapies. Toca 511 is a retroviral replicating vector derived from a cloned Moloney murine leukemia virus with the original ecotropic envelope gene replaced with an amphotropic envelope gene to enable the virus to infect human cells. A modified yeast cytosine deaminase (CD) gene has been inserted into this vector. The expressed CD enzyme catalyzes conversion of antifungal drug 5-flucytosine (administered as investigational extended-release formulation Toca FC) to antineoplastic drug 5-fluorouracil. Toca 5 is a multicenter, randomized, open-label Phase 2/3 trial of Toca 511 and Toca FC versus standard of care (Investigator's choice of single agent lomustine, temozolomide, or bevacizumab) administered to patients undergoing resection for first or second recurrence of glioblastoma or anaplastic astrocytoma. The trial will enroll approximately 370 patients (Phase 2-170 and Phase 3-200). Primary endpoint is overall survival (OS). Key secondary endpoints are safety, objective response rate, clinical benefit rate, progression-free survival, and landmark OS. Key inclusion criteria are age 18-75 years, histologically proven glioblastoma or anaplastic astrocytoma, measurable disease preoperatively of at least 1 cm, candidate for ≥ 80% resection of enhancing tumor based on pre-operative evaluation, KPS ≥ 70. Selected exclusion criteria are enhancing tumor > 5 cm, more than two prior recurrences and prior bevacizumab other than for newly diagnosed glioma. Assays will be performed to evaluate evidence for immunologic mechanisms of disease control, including tumor reactivePBMC measurement by stimulation via ex vivo glioma antigen presentation, flow cytometry based phenotyping of PBMCs with an effector, memory, Treg, and myeloid derived suppressor cell panel. Molecular profiling of resected tumor samples will be correlated with primary and secondary endpoints to identify potential biomarkers for treatment-related response. Toca5is expected to begin enrollment in 3Q 2015.