CART-EGFR-IL13Ra2 cells for the Treatment of IDH Wild-Type, EGFR-Amplified Recurrent Glioblastoma

Inclusion Criteria

• Signed, written informed consent
• Male or female age >= 18 years
• Patients with glioblastoma, IDH-wildtype (as defined by World Health Organization [WHO] 2021 Classification of central nervous system [CNS] Tumors) that has recurred following prior radiotherapy. For patients with tumors harboring methylation of the MGMT promoter, at least 12 weeks must have elapsed since completion of first-line radiotherapy
• Tumor tissue positive for wild-type EGFR amplification by NeoGenomics Laboratories. Archival tumor from patient’s initial surgery at time of original diagnosis or recently collected tumor from time of recurrence are acceptable
• Surgical tumor resection for disease control/management or tumor biopsy to confirm tumor recurrence is clinically indicated in the opinion of the physician-investigator
• Serum creatinine =< 1.5 x upper limit of normal (ULN) or estimated creatinine clearance >= 30 ml/min and not on dialysis
• Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =< 3 x upper limit of normal range
• Total bilirubin =< 2.0 mg/dl, except for patients in whom hyperbilirubinemia is attributed to Gilbert's syndrome (=< 3.0 mg/dl)
• Left ventricular ejection fraction (LVEF) >= 45% confirmed by ECHO/MUGA
• Must have a minimum level of pulmonary reserve defined as =< grade 1 dyspnea and pulse oxygen > 92% on room air
• Karnofsky performance status >= 60%
• Subjects of reproductive potential must agree to use acceptable birth control methods
• ELIGIBILITY CRITERIA FOR RETREATMENT:
• Subject has demonstrated clinical benefit after their initial treatment with CART-EGFR-IL13Ra2 cells, as determined by their physician-investigator
• Retreatment cycle 1 (-R1) only: A formal dose-limiting toxicity (DLT) assessments of the subject’s safety data post initial treatment with CART-EGFR-IL13Ra2 cells has been completed, and the principal investigator (PI)/medical doctor (MD) have confirmed the absence of qualifying DLTs
• Additional retreatment cycles (-R2 on) only: Subjects must have completed their day 28 safety follow-up visit prior to receiving additional retreatment cycles
• Subjects must have a manufactured CART-EGFR-IL13Ra2 cell product available that meets the protocol-defined minimum acceptable dose, and a CSF-ventricular reservoir still in place to allow for intrathecal administration
• Subjects must not have developed new disease complications, deterioration in performance status or overall clinical condition, new laboratory abnormalities, or new toxicities of therapy (either study treatment or prior therapy) that would, in the opinion of the treating investigator, render it unsafe to proceed with the CART-EGFR-IL13Ra2 retreatment. The following are specific conditions that warrant delaying repeat CAR T cell retreatment: * Pulmonary: New requirement for supplemental oxygen or presence of radiographic abnormalities that are concerning for impending pulmonary decompensation. Chest imaging is not required to evaluate for radiographic abnormalities in the absence of suggestive symptoms or exam findings * Cardiac: New cardiac arrhythmia not controlled with medical management. Electrocardiography (EKG) is not required to evaluate for arrhythmia in the absence of suggestive symptoms or exam findings * Hypotension requiring vasopressor support * Active Infection: Positive blood cultures for bacteria, fungus, or virus within 48 hours of CAR T cell administration
• Subjects must have adhered to all required restrictions on pre-study treatment therapy
• Female subjects of child-bearing potential must not be pregnant as assessed by a negative serum beta human chorionic gonadotropin (HCG) test drawn within 14 days prior to the CART-EGFR-IL13Ra2 retreatment
• Subjects must undergo a Respiratory Virus Panel (RVP; inclusive of SARS-CoV-2) within 14 days prior to CAR T retreatment. If the subject is positive for influenza, Tamiflu (registered trademark) or equivalent, should be administered per package insert. The subject must complete treatment prior to receiving CAR T cells. The RVP does not need to be repeated prior to CAR T cell retreatment; however, if influenza signs and symptoms are present, CAR T cell retreatment should be delayed until the subject is asymptomatic. If the subject is positive for another virus on the RVP, CAR T cell retreatment will be delayed for at least 7 days to be sure clinical symptoms of a viral infection do not develop; or longer if clinically appropriate for the respective viral pathogen. If clinical symptoms develop, CAR T cell retreatment will be delayed until resolution of these symptoms

Exclusion Criteria

• Active hepatitis B or hepatitis C infection
• Any other active, uncontrolled infection
• Class III/IV cardiovascular disability according to the New York Heart Association Classification
• Tumors primarily localized to the brain stem or spinal cord
• Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study
• Receipt of bevacizumab within 3 months prior to enrollment
• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to >= 10 mg daily of prednisone. Patients with autoimmune neurological diseases (such as multiple sclerosis [MS] or Parkinson's) will be excluded
• Pregnant or nursing (lactating) women
• History of allergy or hypersensitivity to study product excipients (human serum albumin, dimethyl sulfoxide [DMSO], and dextran 40)