GlioblastomaPhase 1NCT07385846
Pilot Study of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency
A Phase 1 study testing Pembrolizumab and Navifus Focused Ultrasound Sonification in people with Glioblastoma and Mismatch Repair Deficiency, run by Jennifer Leddon at 1 site in United States.
Trial summary
Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Mismatch Repair Deficiency
- What is being tested?
- Pembrolizumab and Navifus Focused Ultrasound Sonification
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2026to 1 Jun 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Jennifer Lesson, MD contact
United States1 site
University of Cincinnati
Cincinnati, Ohio, 45219
UCCC Clinical Trials Office
About this study
Official title: Pilot Study for the Use of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency: A Phase I Clinical Trial
Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency.
Read the detailed description
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
- Conditions
- Glioblastoma, Mismatch Repair Deficiency
- Being tested
- Pembrolizumab, Navifus Focused Ultrasound Sonification
- Medical subject headings
- Glioblastoma, Turcot syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PembrolizumabDrug
Treatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first.
Navifus Focused Ultrasound SonificationDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Pembrolizumab; Device: Navifus Focused Ultrasound Sonification |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
To evaluate overall survival (OS) in patients treated with NaviFUS combined with PEM after repeat surgery for patients with rGBM and MMR deficiency.
Measured: 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.
Measured: Baseline through 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2026
- Study start1 Jun 2026 (estimated)
- Primary completion1 Jun 2028 (estimated)
- Study completion1 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 8 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jennifer Leddon
- Sponsor type
- University, hospital or other
- Collaborators
- NaviFUS Corporation
- Responsible party
- Sponsor-investigator, Jennifer Leddon, University of Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07385846
- Sponsor's protocol ID
- UCCC-BN-25-02
- Status last verified
- Jan 2026
- First submitted
- 26 Jan 2026
- Last updated
- 4 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study for the Use of Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma With Mismatch Repair Deficiency: A Phase I Clinical Trial
- ClinicalTrials.gov ID
- NCT07385846
- Acronym / sponsor ID
- UCCC-BN-25-02
- Conditions
- Glioblastoma, Mismatch Repair Deficiency
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 8 participants (estimated)
- Lead sponsor
- Jennifer LeddonUniversity, hospital or other
- Collaborators
- NaviFUS Corporation
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 1 Jun 2028 (estimated)
- Study completion
- 1 Jun 2030 (estimated)
- First posted
- 4 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Navigated Focused Ultrasound and Pembrolizumab in the Treatment of Recurrent WHO Grade 4 IDH-Wildtype Glioblastoma with Mismatch Repair Deficiency.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Pembrolizumab + focused ultrasound sonication | Experimental | Drug: Pembrolizumab, Device: Navifus Focused Ultrasound SonificationPembrolizumab 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PembrolizumabTreatment dosing will be 200mg of pembrolizumab every three weeks for up to six months or until disease progression, whichever occurs first. | Drug | Pembrolizumab + focused ultrasound sonication |
| Navifus Focused Ultrasound SonificationFocused 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. | Device | Pembrolizumab + focused ultrasound sonication |
Primary outcome
Safety of using navigated focused ultrasound (NaviFUS) CTCAE v6.0
Time frame: Assessed at each study visit from baseline through 2 years.
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
Feasibility of using navigated focused ultrasound (NaviFUS) -CTCAE v6.0 criteria
Time frame: Assessed at each study visit from baseline through 2 years.
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
2 secondary outcomes
Overall survival- standard Kaplan-Meier method and calculated from the date of GBM diagnosis
Time frame: Baseline through 2 years
Progression free survival - standard Kaplan-Meier method and calculated from the date of GBM diagnosis
Time frame: Baseline through 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Jennifer Lesson, MD contact
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Pembrolizumab and Navifus Focused Ultrasound Sonification in people with Glioblastoma and Mismatch Repair Deficiency, run by Jennifer Leddon at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact UCCC Clinical Trials Office (513-584-7698, cancer@uchealth.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of using navigated focused ultrasound (NaviFUS) CTCAE v6.0 (time frame: Assessed at each study visit from baseline through 2 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2026.