Study of Low-Intensity Focused Ultrasound in Combination With Immunotherapy in Newly Diagnosed Unmethylated Glioblastoma

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.

NCT Number	NCT07343986
Lead Sponsor	University of Virginia Collaborators: Focused Ultrasound Foundation, NaviFUS Corporation
Conditions	Glioblastoma (GBM)
Enrollment	12 participants
Start Date	2026-03-23
Primary Completion	2027-12 (estimated)
Study Completion	2028-12 (estimated)
Updated on ClinicalTrials.gov	2026-05-06