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Newly Diagnosed GlioblastomaPhase 2NCT05864534

Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

A Phase 2 study testing Balstilimab, Botensilimab and Liposomal Doxorubicin in people with Newly Diagnosed Glioblastoma and Glioblastoma, Isocitric Dehydrogenase (IDH)-Wildtype, run by Northwestern University at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Balstilimab, Botensilimab and Liposomal Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteUnited States
Study dates
19 Jan 2024to 31 Aug 2031
Phase
Phase 2
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

  • 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
Show all 22Show fewer
  • 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.

Who cannot join

None listed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Northwestern University

    Chicago, Illinois, 60611

Other trials in United States

About this study

Official title: 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.

Read the 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.

Being tested
Balstilimab, Botensilimab, Liposomal Doxorubicin, Sonocloud-9 (SC-9)
Keywords
Immunotherapy, Ultrasound, Blood-brain barrier, Sonocloud, Balstilimab (BAL), Botensilimab (BOT), Doxorubicin (DOX)
Medical subject headings
Glioblastoma, Gliosarcoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BalstilimabDrug

    Also called BAL

    Balstilimab 450 mg IV over 30 minutes every 3 weeks

  • BotensilimabDrug

    Also called BOT

    Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks

  • Liposomal DoxorubicinDrug

    Also called DOX

    Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks

  • Sonocloud-9 (SC-9)Device

    Also called SC-9

    Device activation of 9 ultrasound emitters during IV injection of microbubbles every 3 weeks

Study groups in NCT05864534
Study groupRoleWhat they receive
Blood-brain barrier opening with concomitant BAL, BOT, DOXExperimentalPatients 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.
Receives: Drug: Balstilimab; Drug: Botensilimab; Drug: Liposomal Doxorubicin; Device: Sonocloud-9 (SC-9)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Unacceptable toxicity rate

    Unacceptable toxicity rate in cycle 1 of < 33%

    Measured: 42 days

  2. Landmark survival analyses

    Overall survival and progression-free survival at 12 and 18 months, as well as median progression-free and overall survival.

    Measured: 18 months

Secondary outcomes (2)

  1. Predictive value of phospho-extracellular signal-related kinase (p-ERK) expression

    Predictive value of baseline tissue p-ERK expression for response/benefit of immunotherapy

    Measured: 18 months

  2. Response rate

    Measurement of tumor shrinkage using Response Assessment in Neuro-oncology criteria in those with residual or tumor

    Measured: 18 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted18 May 2023
  2. Study start19 Jan 2024
  3. Primary completion31 Jul 2031 (estimated)
  4. Study completion31 Aug 2031 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05864534
Sponsor's protocol ID
NU23C03
Status last verified
Sep 2026
First submitted
9 May 2023
Last updated
29 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Das R, Verma R, Sznol M, Boddupalli CS, Gettinger SN, Kluger H, Callahan M, Wolchok JD, Halaban R, Dhodapkar MV, Dhodapkar KM. Combination therapy with anti-CTLA-4 and anti-PD-1 leads to distinct immunologic changes in vivo. J Immunol. 2015 Feb 1;194(3):950-9. doi: 10.4049/jimmunol.1401686. Epub 2014 Dec 24.

    PubMed 25539810

  • O'Malley DM, Oaknin A, Monk BJ, Selle F, Rojas C, Gladieff L, Berton D, Leary A, Moore KN, Estevez-Diz MDP, Hardy-Bessard AC, Alexandre J, Opperman CP, de Azevedo CRAS, Randall LM, Feliu WO, Ancukiewicz M, Ray-Coquard I. Phase II study of the safety and efficacy of the anti-PD-1 antibody balstilimab in patients with recurrent and/or metastatic cervical cancer. Gynecol Oncol. 2021 Nov;163(2):274-280. doi: 10.1016/j.ygyno.2021.08.018. Epub 2021 Aug 25.

    PubMed 34452745

  • Treat LH, McDannold N, Zhang Y, Vykhodtseva N, Hynynen K. Improved anti-tumor effect of liposomal doxorubicin after targeted blood-brain barrier disruption by MRI-guided focused ultrasound in rat glioma. Ultrasound Med Biol. 2012 Oct;38(10):1716-25. doi: 10.1016/j.ultrasmedbio.2012.04.015. Epub 2012 Jul 19.

    PubMed 22818878

  • Beccaria K, Sabbagh A, de Groot J, Canney M, Carpentier A, Heimberger AB. Blood-brain barrier opening with low intensity pulsed ultrasound for immune modulation and immune therapeutic delivery to CNS tumors. J Neurooncol. 2021 Jan;151(1):65-73. doi: 10.1007/s11060-020-03425-8. Epub 2020 Feb 28.

    PubMed 32112296

  • Duerinck J, Schwarze JK, Awada G, Tijtgat J, Vaeyens F, Bertels C, Geens W, Klein S, Seynaeve L, Cras L, D'Haene N, Michotte A, Caljon B, Salmon I, Bruneau M, Kockx M, Van Dooren S, Vanbinst AM, Everaert H, Forsyth R, Neyns B. Intracerebral administration of CTLA-4 and PD-1 immune checkpoint blocking monoclonal antibodies in patients with recurrent glioblastoma: a phase I clinical trial. J Immunother Cancer. 2021 Jun;9(6):e002296. doi: 10.1136/jitc-2020-002296.

    PubMed 34168003

  • Shimozaki K, Sukawa Y, Sato Y, Horie S, Chida A, Tsugaru K, Togasaki K, Kawasaki K, Hirata K, Hayashi H, Hamamoto Y, Kanai T. Analysis of risk factors for immune-related adverse events in various solid tumors using real-world data. Future Oncol. 2021 Jul;17(20):2593-2603. doi: 10.2217/fon-2020-0861. Epub 2021 Apr 21.

    PubMed 33878916

  • Kim KS, Habashy K, Gould A, Zhao J, Najem H, Amidei C, Saganty R, Arrieta VA, Dmello C, Chen L, Zhang DY, Castro B, Billingham L, Levey D, Huber O, Marques M, Savitsky DA, Morin BM, Muzzio M, Canney M, Horbinski C, Zhang P, Miska J, Padney S, Zhang B, Rabadan R, Phillips JJ, Butowski N, Heimberger AB, Hu J, Stupp R, Chand D, Lee-Chang C, Sonabend AM. Fc-enhanced anti-CTLA-4, anti-PD-1, doxorubicin, and ultrasound-mediated blood-brain barrier opening: A novel combinatorial immunotherapy regimen for gliomas. Neuro Oncol. 2024 Nov 4;26(11):2044-2060. doi: 10.1093/neuonc/noae135.

    PubMed 39028616

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Balstilimab, Botensilimab and Liposomal Doxorubicin in people with Newly Diagnosed Glioblastoma and Glioblastoma, Isocitric Dehydrogenase (IDH)-Wildtype, run by Northwestern University 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 22 inclusion and 0 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: under way, not looking for participants, as of the sponsor's last update on 29 Sep 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Unacceptable toxicity rate (time frame: 42 days). 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?

On the ClinicalTrials.gov record for NCT05864534, which also lists 7 linked publications.

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 29 Sep 2026.

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