CTIM-25. PHASE2B/3 STUDY OF NEOANTIGEN-SPECIFIC T CELL IMMUNOTHERAPY IN NEWLY DIAGNOSED O6 – METHYLGUANINE METHYLTRANSFERASE UNMETHYLATED (MGMT -) GLIOBLASTOMA

Abstract MGMT- glioblastoma (GBM) is the most common malignant primary brain tumor, yet outcomes have not improved in decades despite intensive investigations. TVI-AST-008 is a randomized clinical trial of a novel neoantigen-specific T cell immunotherapy regimen proven invariably curative in rodent models and clinically effective in trials of patients with relapsed/resistant GBM. TVAX neoantigen-specific T cell immunotherapy exploits the fact that cancer cells express neoantigens, and adoptive transfer can bypass the immunosuppressive milieu near the resection cavity. In this manner, TVAX effector T cells initiate apoptosis in any residual GBM. After pathologic confirmation, autologous GBM tumor tissue sent to the TVAX GMP manufacturing facility is irradiated and utilized for proprietary vaccine production. Patients are vaccinated with a series of two intradermal injections and the resulting cancer neoantigen-specific T cells are harvested by leukapheresis. These T cells are activated and proliferated ex vivo by TVAX manufacturing to generate effector T cells. These are re-infused following standard radio-chemotherapy, followed by low-dose interleukin-2 to further stimulate T cell proliferation. In the study, MGMT- GBM patients are randomly assigned to treatment or control arms. Patients in the treatment arm undergo vaccination, then standard concurrent IMRT-chemotherapy, followed by re-infusion of TVAX autologous effector T cells. Patients in the control arm undergo standard IMRT-chemotherapy followed by adjuvant chemotherapy with temozolomide. TVI-AST-008 is an ongoing, randomization-controlled study with Fast Track designation from the FDA. The primary end point is overall survival. Additional end points include progression free survival, safety and immune response. Patients are followed with physical exams and surveillance MRI for evidence of disease progression. The trial is targeted for 15 centers in the US.