Neoantigen-specific Adoptive T Cell Therapy for Glioblastoma, IND-BB-13135, protocol submitted 04/25/2020

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TVAX Biomedical has developed a novel form of immunotherapy, neoantigen-specific adoptive T cell therapy (NACT), that has the potential to significantly improve outcomes for newly diagnosed glioblastoma patients. There is a significant unmet medical need for safer, more effective treatments for glioblastoma. Surgery combined with temozolomide chemoradiotherapy provides modest survival benefit and is not curative. Moreover, the O6-methylguanine methyltransferase negative (MGMT unmethylated) subgroup, which is comprised by approximately 60% of glioblastoma patients, is relatively resistant to the temozolomide component of chemoradiotherapy. NACT combines 1) neoantigen-specific cancer cell/immunological adjuvant vaccination, 2) adoptive transfer of ex vivo-activated cancer neoantigen-specific effector T cells and 3) interleukin 2 to produce a treatment that has the potential to be effective against surgically resectable glioblastomas. As an autologous immunotherapy, NACT generates only transient (24-72 hours) grade 1 and 2 toxicity. The patients’ own cancer cells are combined into a vaccine with a strong immunological adjuvant (granulocyte macrophage colony-stimulating factor) to produce a polyclonal cancer neoantigen-specific immune response that significantly increases the number of cancer neoantigen-specific effector T cell precursors in the patient’s body. These cancer neoantigen-specific T cells can be harvested from the blood and stimulated ex vivo with T cell activating agents. The result is the generation of high numbers of cancer neoantigen-specific effector T cells that have the ability to orchestrate effective cancer cell killing following their return to the patient’s body. NACT is most effective when the patient has a healthy immune system and minimal disease. This randomized 50-subject study is designed to compare the combination of NACT and standard therapy to standard therapy alone as a treatment for newly diagnosed MGMT unmethylated glioblastoma patients. Immunotherapy would be maximal when used to treat patients with relatively healthy immune systems and disease that has been reduced by standard chemoradiotherapy. Benefit may also accrue from standard therapy’s reduction or reversal of immunosuppression. Success is anticipated because preclinical glioma studies and previous phase 1/2a clinical studies with recurrent high-grade astrocytoma patients who had failed surgery, radiotherapy and chemotherapy provided evidence that NACT is safe and effective and could be curative. This phase 2b clinical trial will be performed in collaboration with the neuro-oncology and neurosurgical team in the Division of Medical Oncology - Neuro-Oncology, Department of Medicine at the Rutgers Cancer Institute of New Jersey. Success in this clinical trial will lead to performance of a larger phase 2/3 clinical trial designed to generate data that could lead to marketing approval by the FDA and subsequent commercialization of NACT as a treatment for MGMT unmethylated glioblastoma. This will be the first time that this treatment will have been tested for safety, efficacy, and immunological effects in patients with newly diagnosed MGMT unmethylated glioblastoma.