Phase I Clinical Trial of Anti-CD3 × Anti-EGFR Bispecific-armed T Cells (EGFR BATs) and Low-Intensity Focused Ultrasound (LIFU) Blood-brain Barrier Opening in Patients With MGMT Unmethylated Glioblastoma (GBM)
This is a phase 1 study for patients with newly diagnosed MGMT unmethylated IDH wild-type glioblastoma utilizing autologous activated T-cells armed with bispecific antibody (EGFR-BATs) that recognize the tumor. The investigators hypothesized that the combination of infusions of EGFR BATs and low-intensity focused ultrasound would induce blood-brain barrier opening and increase the permeability of the adoptive immunotherapy. The investigators will radiolabel the EGFR BATs with 89Zr-oxine for subsequent PET imaging to determine the trafficking and uptake of this approach. There is a concern that several infusions of EGFR BATs before BBB opening could change the immune tumor microenvironment that would not allow a permissive BBB after LIFU. Therefore, Arm A will have two LIFU with BBB opening after the 4th and the 8th infusion, and Arm B will have three LIFU with BBB opening after the 1st, 4th, and 8th infusions. This study will determine the safety and feasibility of the combination of low-intensity focused ultrasound (LIFU) with microbubbles BBB opening and EGFR BATs and the access of the adoptive cell immunotherapy to the tumor microenvironment to inform future studies.
• Newly diagnosed supratentorial glioblastoma or gliosarcoma IDH wildtype and MGMT unmethylated that express EGFR (score ≥ 1 by IHC)) and confirmed by UVA pathology review.
• Age ≥ 18 and ≤ 70 years at the time of signing informed consent.
• Karnofsky Performance Status (KPS) ≥ 70.
• Be willing and able to provide written informed consent for the trial.
• Females of childbearing potential, and males, must be willing to use an effective method of contraception.
• Maximal surgical debulking of the tumor was performed where residual contrast enhancement is 2 cm3 or less on immediate post-operative MRI. Intraoperative post-resection MRI is acceptable.
• Able to communicate during the LIFU BBB opening procedure.
• BBB opening target(s) must lie in non-eloquent area(s).
• The brain tumor to be treated must be in the treatment envelope of the NaviFUS system with a minimum distance of 30 mm from the inner skull table.
⁃ Females of childbearing potential should have a negative serum pregnancy test. Males who are partners of females of childbearing potential must agree to use an acceptable method of contraception throughout the study and for 1 month following completion of the EGFR BATs infusions.
⁃ Demonstrate adequate organ function as defined in Table 1. All screening labs should be performed within 10 days before leukapheresis.