Safety and Immunogenicity of Personalized Genomic Vaccine and Tumor Treating Fields (TTFields) to Treat Glioblastoma

Phase I Study of Tumor Treatment Fields and a Personalized Mutation-derived Tumor Vaccine in Patients With Newly Diagnosed Glioblastoma (GCO 17-0566)

The purpose of this study is to use precision medicine in the form of a vaccine, a mutation-derived tumor antigen vaccine (MTA-based vaccine) in combination with standard care treatment of glioblastoma (GBM) and Tumor Treating Fields (TTFields).

The study is designed to determine whether this treatment combination is well tolerated and safe.

This is a single-arm, single institution phase 1a / 1b study to test the safety, tolerability, and immunogenicity of MTA-based personalized vaccine in patients with newly diagnosed GBM along with the use of continual TTFields. MTA-based personalized vaccine is prepared in the laboratory with several peptides based on each patient's own tumor sequence.

The vaccine is given after the radiation and chemotherapy portion of the treatment, in the maintenance phase of temozolomide in conjunction with the TTFields.

Inclusion Criteria:

• Age ≥ 18
• Histological confirmation of GBM (WHO grade IV).
• Stable disease after treatment of radiation with concurrent chemotherapy. If the disease is not stable or progresses while in the study the patient is allowed to continue the study receiving the vaccine if the tumor gets controlled by other modality treatment(s)
• Must have received maximal debulking surgery and undergo radiotherapy concomitant with Temozolomide (45-70Gy)
• Life expectancy > 16 weeks
• Performance status of 0-2 as determined by Eastern Cooperative Oncology Group (ECOG) and/or Karnofsky Performance Status (KPS) 70-100
• First vaccine treatment start date at least 4 weeks out but not more than 8 weeks from the last dose of concomitant Temozolomide or radiotherapy
• Must have archival tumor tissue that is sufficient quantity and quality for sequencing
• Have adequate bone marrow function
• Requires Dexamethasone ≤ 4mg daily on a stable dose
• Acceptable hematologic, hepatic, and renal function and these tests must be performed within 14 days prior to study
• Must be deemed competent to give informed consent
• Must agree to use two effective forms of contraception beginning at least four (4) weeks prior to study entry, and continuing to do so for the duration of participation in the study

Exclusion Criteria:

• Progression of disease at time of screening
• Implanted pacemaker, programmable shunts, defibrillator, deep brain stimulator, other implanted electronic devices in the brain, or documented clinically significant arrhythmias
• Infra-tentorial tumor or multifocal disease
• History of hypersensitivity reaction to Temozolomide or a history of hypersensitivity to Decarbazine (DTIC)
• Receiving any other investigational agents. Patient is allowed to get another investigational agent and to continue receiving the vaccine only if the disease progresses while in the study and the other investigational agent is a reasonable choice to treat the patient
• Active cancer at the time of screening
• Prior history of unrelated neoplastic disease, and having received systemic therapy for the secondary malignancy within the twelve (12) month period preceding the screening evaluation.
• History of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS), chronic hepatitis B or hepatitis C or is otherwise reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression
• History of, or is reasonably suspected to meet criteria for the diagnosis of a known congenital or acquired disorder causing systemic immunosuppression; or the subject is currently receiving any drug or supplement which is known to be associated with systemic immune suppression including those drugs which are prescribed for solid organ or stem cell transplant, autoimmune/inflammatory disorders, or other related medical conditions
• History of, or is reasonably suspected to meet criteria for the diagnosis of a systemic auto-immune/inflammatory disease or other autoimmune disorder with the exception of: Vitiligo, diabetes, or thyroid dysfunction
• Less than 18 years of age, or otherwise unable to give informed consent due to minor status
• Prisoner, as defined by [45 CFR 46.303(c)]
• Cognitively impaired, and unable to give informed consent
• Pregnant, as defined by a presumptive sign of pregnancy such as missed menses or a positive pregnancy test [45 CFR 46.203(b)]
• Requires or is likely to require more than a 2-week course of corticosteroids of >4mg