Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

NCT05864534 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: NU23C03
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Newly Diagnosed Glioblastoma; Glioblastoma, Isocitric Dehydrogenase (IDH)-Wildtype; Gliosarcoma; Glioblastoma Multiforme

Keywords

Immunotherapy; Ultrasound; Blood-brain barrier; Sonocloud; Balstilimab (BAL); Botensilimab (BOT); Doxorubicin (DOX)

Outcome Measures

Primary Outcomes (2)

• Unacceptable toxicity rate

  Unacceptable toxicity rate in cycle 1 of \< 33%

  42 days

• Landmark survival analyses

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

  18 months

Secondary Outcomes (2)

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

  18 months

• Response rate

  18 months

Other Outcomes (2)

• Patterns of recurrence

  18 months

• Immune profile

  12 months

Study Arms (1)

Blood-brain barrier opening with concomitant BAL, BOT, DOX

EXPERIMENTAL

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; Drug: Botensilimab; Drug: Liposomal Doxorubicin; Device: Sonocloud-9 (SC-9)

Interventions

Balstilimab DRUG

Balstilimab 450 mg IV over 30 minutes every 3 weeks

Also known as: BAL

Blood-brain barrier opening with concomitant BAL, BOT, DOX

Botensilimab DRUG

Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks

Also known as: BOT

Blood-brain barrier opening with concomitant BAL, BOT, DOX

Liposomal Doxorubicin DRUG

Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks

Also known as: DOX

Blood-brain barrier opening with concomitant BAL, BOT, DOX

Sonocloud-9 (SC-9) DEVICE

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

Also known as: SC-9

Blood-brain barrier opening with concomitant BAL, BOT, DOX

Eligibility Criteria

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

You may qualify if:

• 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
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Northwestern University: lead
• Agenus Inc.: collaborator
• CarThera: collaborator

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Related Publications (7)

• 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.

  PMID: 25539810 BACKGROUND

• 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.

  PMID: 34452745 BACKGROUND

• 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.

  PMID: 22818878 BACKGROUND

• 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.

  PMID: 32112296 BACKGROUND

• 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.

  PMID: 34168003 BACKGROUND

• 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.

  PMID: 33878916 BACKGROUND

• 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.

  PMID: 39028616 DERIVED

MeSH Terms

Conditions

Glioblastoma; Gliosarcoma

Interventions

balstilimab; liposomal doxorubicin

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

Study Officials

• Adam Sonabend, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

• Roger Stupp, MD

  Northwestern University

  STUDY DIRECTOR

Central Study Contacts

Neurological Surgery

CONTACT

(312) 695-8143; braintumortrials@nm.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 9, 2023
• First Posted: May 18, 2023
• Study Start: January 31, 2024
• Primary Completion: May 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: October 3, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)