Pilot Study of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency

NCT07385846 | Not Yet Recruiting Phase 1 DMC FDA Device

• 1 other identifier: UCCC-BN-25-02
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency.

Conditions

Glioblastoma; Mismatch Repair Deficiency

Outcome Measures

Primary Outcomes (2)

• Safety of using navigated focused ultrasound (NaviFUS) CTCAE v6.0

  To evaluate the safety of using navigated focused ultrasound (NaviFUS) combined with pembrolizumab (PEM) after repeat surgery for patients with recurrent glioblastoma (rGBM) and mismatch repair (MMR) deficiency. Given that NaviFUS and PEM have defined intracranial dosing, no dose-escalation scheme will be employed. A CTCAE v6.0 grade 4 or higher toxicity probably or definitely attributable (see Section 13.2.3) to the administration of NaviFUS or PEM will be used as the definition for unacceptable toxicity

  Assessed at each study visit from baseline through 2 years.

• Feasibility of using navigated focused ultrasound (NaviFUS) -CTCAE v6.0 criteria

  To evaluate feasibility of using navigated focused ultrasound (NaviFUS) combined with pembrolizumab (PEM) after repeat surgery for patients with recurrent glioblastoma (rGBM) and mismatch repair (MMR) deficiency. Given that NaviFUS and PEM have defined intracranial dosing, no dose-escalation scheme will be employed. A CTCAE v6.0 grade 4 or higher toxicity probably or definitely attributable (see Section 13.2.3) to the administration of NaviFUS or PEM will be used as the definition for unacceptable toxicity

  Assessed at each study visit from baseline through 2 years.

Secondary Outcomes (2)

• Overall survival- standard Kaplan-Meier method and calculated from the date of GBM diagnosis

  Baseline through 2 years

• Progression free survival - standard Kaplan-Meier method and calculated from the date of GBM diagnosis

  Baseline through 2 years

Other Outcomes (2)

• Baseline levels of markers of immune function and genetic repair

  Baseline

• radiographic response to treatment in patients with postsurgical residual disease as determined via mRANO criteria

  Baseline

Study Arms (1)

Pembrolizumab + focused ultrasound sonication

EXPERIMENTAL

Pembrolizumab along with focused ultrasound sonication following surgery for recurrent glioblastoma. Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first. The primary endpoint will be safety and tolerability, with secondary efficacy endpoints and exploratory biomarker and radiographic analyses.

Drug: Pembrolizumab; Device: Navifus Focused Ultrasound Sonification

Interventions

Pembrolizumab DRUG

Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first.

Pembrolizumab + focused ultrasound sonication

Navifus Focused Ultrasound Sonification DEVICE

Focused Ultrasound Sonification- Post Pembro infusion, patients will received NaviFUS sonication to the complete volume of the tumor resection bed (as limited by anatomic constraints relative to the tumor extension) following microbubble (Bracco Imaging, SonoVue® or Lumason®; 0.1 mL/Kg; maximum 4.8 mL) administration on a 2-minute schedule. The NaviFUS procedure will be guided using the compatible navigation system, Medtronic StealthStation®. Microbubble administration and operation of the NaviFUS unit will be completed by qualified delegated study investigators. Treatment sessions will occur every 3 weeks for 6 months or until evidence of disease progression, whichever occurs first. A 6-month treatment duration was determined in order to report a 6-month PFS rate as one of the secondary outcomes for this study population.

Pembrolizumab + focused ultrasound sonication

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient previously diagnosed with WHO grade 4 IDH-wildtype GBM, determined through genomic and/or histopathological analysis.
• Prior treatment for GBM with surgical resection and standard of care TMZ and radiation therapy.
• Patient who has undergone repeat surgery (including biopsy or resection) for rGBM.
• MMR deficiencies confirmed per standard of care immunohistochemical analysis or Next Generation Sequencing (NGS) of the patient's surgical sample from the time of initial GBM diagnosis or recurrence.
• Area of sonication using the NaviFUS platform is \>30 mm from the skull surface, assessed on the Investigator's review of the screening MRI.
• Age ≥18 years.
• Karnofsky Performance Scale (KPS) \>70.
• Adequate organ and marrow function:
• Leukocytes ≥2,500/mm3 Absolute Neutrophil Count ≥1,500/mm3 Absolute Lymphocyte Count ≥800/mm3 Platelets ≥100,000/mm3 Hemoglobin ≥8 g/dL
• Negative serum or urine pregnancy test in a female patient of childbearing potential.
• Patient or a legally-authorized representative must provide study-specific informed consent.

You may not qualify if:

• Multifocal or leptomeningeal disease observed at the time of GBM recurrence.
• Patient for whom the repeat surgical cavity is ≤30 mm from the skull surface or otherwise not reasonably accessible for sonification using the NaviFUS platform, assessed on screening MRI.
• Patient with a prior or concurrent malignancy that is deemed to be clinically significant in the context of rGBM.
• Patient receiving concurrent treatment with an immune checkpoint inhibitor, other investigational agent, or live vaccine administered within 14 days prior to the first dose of trial treatment.
• Prior treatment with an immune checkpoint inhibitor agent.
• Period of less than 28 days from the time of the patient's receipt of other systemic anti-cancer therapies to the proposed date of first trial treatment.
• Treatment with systemic corticosteroids at an increased dose or dose of ≥10 mg of prednisone (or equivalent) daily within the 5 days prior to starting trial treatment, or treatment with systemic corticosteroids for other indications.
• Patient with a history of organ transplant or autoimmune disorder requiring active immunosuppression.
• Patient with current recreational drug use or a history of substance use disorder.
• Patient with an active concurrent comorbidity that, in the opinion of the Investigator, would pose a safety concern for the patient's participation in this clinical trial.

Sponsors & Collaborators

• Jennifer Leddon: lead
• NaviFUS Corporation: collaborator

Study Sites (1)

University of Cincinnati

Cincinnati, Ohio, 45219, United States

Location

MeSH Terms

Conditions

Glioblastoma; Turcot syndrome

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

UCCC Clinical Trials Office

CONTACT

513-584-7698; cancer@uchealth.com

Jennifer Lesson, MD

CONTACT

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Model Details: In this phase I clinical trial, 6-8 patients with recurrent glioblastoma and identified mismatch repair (MMR) deficiency will be administered pembrolizumab along with focused ultrasound sonication following surgery for recurrent glioblastoma.

Study Record Dates

• First Submitted: January 26, 2026
• First Posted: February 4, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2030
• Last Updated: February 4, 2026

Record last verified: 2026-01

Locations

US (1)