A Phase 1 interventional study of Pembrolizumab and Navifus Focused Ultrasound Sonification in Glioblastoma and Mismatch Repair Deficiency, sponsored by Jennifer Leddon. Not yet recruiting at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-02-04.
Sponsored by Jennifer Leddon · Phase 1, Interventional, and Treatment
Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency.
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. 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
1,920 studies on the registry are indexed under Glioblastoma; 450 are open to participants now.
This study's planned enrollment of 8 is below the median of 36 across 1,618 interventional studies indexed under Glioblastoma.
Browse Glioblastoma studies →This is the only study on the registry with Jennifer Leddon as lead sponsor.
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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
Exclusion Criteria:
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
Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first.
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.
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
Time frame: 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
Time frame: Assessed at each study visit from baseline through 2 years.
Overall survival- standard Kaplan-Meier method and calculated from the date of GBM diagnosis
To evaluate overall survival (OS) in patients treated with NaviFUS combined with PEM after repeat surgery for patients with rGBM and MMR deficiency.
Time frame: Baseline through 2 years
Progression free survival - standard Kaplan-Meier method and calculated from the date of GBM diagnosis
To evaluate progression free survival (PFS) in patients treated with NaviFUS combined with PEM after repeat surgery for patients with rGBM and MMR deficiency.
Time frame: Baseline through 2 years
Baseline levels of markers of immune function and genetic repair
To evaluate levels of baseline tumor markers related to immune and genetic repair function, including PD-L1, microsatellite instability (MSI), and tumor mutational burden (TMB).
Time frame: Baseline
radiographic response to treatment in patients with postsurgical residual disease as determined via mRANO criteria
To evaluate radiographic treatment response according to Modified Response Assessment in Neuro-Oncology (mRANO) criteria prior to treatment with NaviFUS combined with PEM in patients with postsurgical residual tumor.
Time frame: Baseline
Plan to share: Undecided
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