A Specific Type of CAR T-cells (CART-EGFRvIII Cells) and Pembrolizumab in Treating Patients with MGMT-Unmethylated Glioblastoma

Inclusion Criteria

• Newly diagnosed glioblastoma (GBM) that is histologically confirmed by pathology review of surgically resected tissue
• Undergone tumor resection
• No prior systemic therapies, radiation, tumor-treating fields, or intratumoral therapeutic agents including Gliadel wafers are allowed. Tumor resection must be the only tumor-directed treatment that the patient has received for glioblastoma
• Tumor tissue is positive for EGFRvIII expression, as performed by the University of Pennsylvania’s in-house fusion transcript panel (RNA-based assay using Illumina HiSeq platform). Outside EGFRvIII expression testing is not allowed
• Tumor tissue is negative for MGMT promoter methylation (i.e. the tumor is MGMT-unmethylated), as performed by the University of Pennsylvania’s in-house pyrosequencing protocol. Outside MGMT testing is not allowed
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Provides written informed consent
• White blood count >= 2500/mm^3
• Platelets >= 100,000/mm^3 without transfusion or growth factor support
• Hemoglobin >=9.0 g/dL without transfusion or growth factor support
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) within 2.5 x upper normal limit
• Gamma glutamyl transferase (GGT) within 2.5 x upper normal limit
• Lactate dehydrogenase (LDH) within 2.5 x upper normal limit
• Alkaline phosphatase within 2.5 x upper normal limit
• Total bilirubin =< 2.0 mg/dL
• Serum creatinine =< 1.5 x upper limit of normal
• Adequate cardiac function (left ventricular ejection fraction [LVEF] >= 45%)
• Subjects of reproductive potential must agree to use acceptable birth control methods

Exclusion Criteria

• Pregnant or lactating women
• Inadequate venous access for or contraindications to leukapheresis
• Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection, or other active, uncontrolled infection
• History of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and dextran 40)
• History of severe hypersensitivity reactions to other monoclonal antibodies which in the opinion of the investigator may post an increased risk of serious infusion reactions
• Requirement for immunosuppressive agents including but not limited to cyclosporine, mycophenolate mofetil (MMF), tacrolimus, rapamycin, or anti-TNF agents within 4 weeks of eligibility confirmation by the physician-investigator
• Subjects with a history of known or suspected, severe or uncontrolled autoimmune or connective tissue disease. Patients with vitiligo, controlled type 1 diabetes mellitus (on stable insulin dose), residual autoimmune-related hypothyroidism (due to autoimmune condition only requiring hormone replacement), or psoriasis (not requiring systemic treatment), or conditions not expected to recur in the absence of an external trigger, are permitted to enroll
• Known history or current interstitial lung disease or non-infectious pneumonitis
• Prior allogenic bone marrow or solid organ transplant
• Any concurrent malignancy other than non-melanoma skin cancer that has been curatively treated, or carcinoma in situ of the cervix or bladder that has been curatively treated. For any prior invasive malignancy, at least 5 years must have elapsed since curative therapy and patients must not have received any radiation to the brain. Monoclonal gammopathy of undetermined significance (MGUS) is permitted
• Any uncontrolled active medical or psychiatric disorder that would preclude participation as outlined
• Severe, active co-morbidity in the opinion of the physician-investigator would preclude participation in this study, including but not limited to the following: * Unstable angina within 6 months prior to eligibility confirmation by the physician-investigator * Transmural myocardial infarction within the last 6 months prior to eligibility confirmation by the physician-investigator * New York Heart Association grade II or greater congestive heart failure requiring hospitalization within 12 months prior to eligibility confirmation by the physician-investigator ** Note: Please refer to New York Heart Association (NYHA) Functional Classification * Serious and inadequately controlled cardiac arrhythmia * Serious or non-healing wound, ulcer, or history of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to eligibility confirmation by the physician-investigator, with the exception of the craniotomy for tumor resection