Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

May 8, 2026 updated by: Adam M Sonabend, Northwestern University

A Phase 2a Trial of Immune Modulation in Combination With Ultrasound-mediated Blood Brain Barrier Opening in Patients With Newly Diagnosed Glioblastoma

Brain tumor treatment is hampered by the blood-brain barrier (BBB). This barrier prevents drugs carried in the bloodstream from getting into the brain. If the BBB can be opened, making it temporarily more permeable, drugs may able to better reach the brain tumor. In this trial we will implant a novel device with 9 ultrasound emitters, allowing temporary and reversible opening of the BBB to maximize brain penetration of drugs that modulate the immune system. The device will be implanted after radiation is completed. Immune modulating drugs will be given every 3 weeks in conjunction with activation of the device to open the BBB.

The objectives of this trial are to establish whether it is safe and feasible to administer immune modulating drugs in this manner, and identify whether the treatment is effective in treating glioblastoma.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Eligible patients will undergo implant of the Soncloud-9 device within 1-5 weeks of completion of radiotherapy. About 1-3 weeks after surgery, patients will undergo sonication and intravenous administration of balstilimab, botensilimab and liposomal doxorubicin. Brain MRI will be done to quantify extent of blood brain barrier opening. The dose for balstilimab is 450 mg every 3 weeks. The dose for botensilimab is 1mg/kg every 6 weeks. The dose for liposomal doxorubicin is 30 mg every 3 weeks. Sonication and administration of study agents will continue every 3 weeks (21 days= 1 cycle) for a total of 9 cycles (approx. 6 months). Additional cycles may be considered if deemed beneficial and in the patient's best interest. Blood samples for circulating tumor DNA will also be collected before and after each sonication. The first 6 patients will comprise a safety run-in cohort with intensified safety monitoring through the end of the second cycle.

Study Type

Interventional

Enrollment (Estimated)

25

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Northwestern University
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Have newly diagnosed pathologically proven glioblastoma, isocitric dehydrogenase-1/2 wild-type
  • Tumor with methyl guanine methyl transferase (MGMT) gene promoter unmethylated
  • Available paraffin embedded tumor tissue for the study
  • Have completed standard radiotherapy with or without temozolomide
  • 18 years of age or older
  • Able to undergo contrast-enhanced MRI
  • Have an Eastern Cooperative Oncology Group/World Health Organization performance status ≤ 2
  • Size and location of the residual tumor and/or resection cavity must allow to be able to be covered by the sonication field
  • Have not received any prior treatment with immunotherapeutic agents treatments for glioblastoma or other indications
  • Have the ability to understand and willingness to sign a written informed consent prior to registration on study.
  • Be willing and able to comply with the protocol.
  • Have adequate organ and bone marrow function
  • Agree to use adequate contraception if appropriate

Exclusion Criteria: Patients will be ineligible if they have:

  • Multifocal tumor (unless all localized in a 50-mm diameter area accessible to ultrasound field) or tumor located in the posterior fossa.
  • Uncontrolled epilepsy.
  • Received other investigational agents within 2 weeks of registration
  • Received prior therapy with or have history of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in this study.
  • Contraindication to checkpoint inhibitor therapy (e.g., history of autoimmune disease)
  • Uncontrolled illness
  • History of active malignancy other than the brain tumor within 12 months prior to registration.
  • Are pregnant or breastfeeding.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Blood-brain barrier opening with concomitant BAL, BOT, DOX
Patients will undergo implantation of Sonocloud-9 after completion of radiotherapy. Within 21 days after implant, ultrasound-based BBB opening with concomitant administration of DOX (30 mg) + BAL (450 mg) every 3 weeks, and BOT (dose 1mg/kg) every 6 weeks will be initiated.
Drug: Balstilimab
Balstilimab 450 mg IV over 30 minutes every 3 weeks
Other Names:
  • BAL
Drug: Botensilimab
Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks
Other Names:
  • BOT
Drug: Liposomal Doxorubicin
Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks
Other Names:
  • DOX
Device: Sonocloud-9 (SC-9)
Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks
Other Names:
  • SC-9

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Unacceptable toxicity rate
Time Frame: 42 days
Unacceptable toxicity rate in cycle 1 of < 33%
42 days
Landmark survival analyses
Time Frame: 18 months
Overall survival and progression-free survival at 12 and 18 months, as well as median progression-free and overall survival.
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Predictive value of phospho-extracellular signal-related kinase (p-ERK) expression
Time Frame: 18 months
Predictive value of baseline tissue p-ERK expression for response/benefit of immunotherapy
18 months
Response rate
Time Frame: 18 months
Measurement of tumor shrinkage using Response Assessment in Neuro-oncology criteria in those with residual or tumor
18 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Patterns of recurrence
Time Frame: 18 months
Patterns of recurrence by magnetic resonance imaging related to sonication field
18 months
Immune profile
Time Frame: 12 months
Analysis of nucleic acid/exosomes and peripheral blood cell for correlation with progression-free survival
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Northwestern University

Collaborators

Agenus Inc.
CarThera

Investigators

  • Principal Investigator: Adam Sonabend, MD, Northwestern University
  • Study Director: Roger Stupp, MD, Northwestern University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 19, 2024

Primary Completion (Estimated)

July 31, 2031

Study Completion (Estimated)

August 31, 2031

Study Registration Dates

First Submitted

May 9, 2023

First Submitted That Met QC Criteria

May 9, 2023

First Posted (Actual)

May 18, 2023

Study Record Updates

Last Update Posted (Actual)

May 13, 2026

Last Update Submitted That Met QC Criteria

May 8, 2026

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NU23C03

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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