RecruitingPhase 1NCT07343986

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

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)

Sponsor

University of Virginia

Enrollment

12 participants

Start Date

Jan 1, 2026

Study Type

INTERVENTIONAL

Conditions

Glioblastoma (GBM)

Summary

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.

Eligibility

Min Age: 18 YearsMax Age: 70 Years

Plain Language Summary

Simplified for easier understanding

This study is testing a new combination treatment for a specific type of brain cancer called glioblastoma (GBM) that has not responded to a common chemotherapy approach. The treatment combines low-intensity focused ultrasound (which temporarily opens the brain's protective barrier to let drugs in more effectively) with an immunotherapy that uses your own modified immune cells. **You may be eligible if...** - You are 18–70 years old with newly diagnosed glioblastoma or gliosarcoma that is IDH wildtype and MGMT unmethylated - Your tumor expresses a protein called EGFR - You have had maximal surgical removal of the tumor - You are in good general health (Karnofsky score of 70 or above) **You may NOT be eligible if...** - You have another active cancer (within the past 2 years) - Your tumor is in the brainstem or cerebellum, or has spread to the lining of the brain - You have a pacemaker, certain metal implants, or are claustrophobic - You have had a heart attack or stroke in the past year, or have heart failure - You are pregnant or breastfeeding - You have HIV or active hepatitis B or C - You have already received treatment for GBM other than surgery Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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