Neoplasms

All Conditions

Rare Diseases

Glioblastoma

Gliosarcoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Doxorubicin

Liposomal doxorubicin

Immunomodulating Agents

Anti-Bacterial Agents

Antibiotics, Antitubercular

Enzyme Inhibitors

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.

Balstilimab 450 mg IV over 30 minutes every 3 weeks

Balstilimab

Botensilimab1mg/kg mg IV over 30 minutes every 6 weeks

Botensilimab

Liposomal Doxorubicin 30 mg IV over 30 minutes every 3 weeks

Liposomal Doxorubicin

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

Sonocloud-9 (SC-9)

Christina Amidei

Nicole Morud

Adam Sonabend, MD

Roger Stupp, MD

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.

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.

Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma

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

Patterns of recurrence by magnetic resonance imaging related to sonication field

Analysis of nucleic acid/exosomes and peripheral blood cell for correlation with progression-free survival

Unacceptable toxicity rate in cycle 1 of \< 33%

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

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

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

Agenus Inc.

CarThera

Northwestern University

Principal Investigator

Symptoms and General Pathology

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Recurrence

Uterine Cervical Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Micronutrients

Hematinics

Vitamins

Antibodies

Antibodies, Monoclonal

Gemcitabine

Vinorelbine

Irinotecan

Pemetrexed

Topotecan

Immunoglobulins

Antimetabolites

Topoisomerase I Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Tubulin Modulators

Antimitotic Agents

Folinic Acid

Folate

Vitamin B9

300 mg IV once every 3 weeks for up to 24 months

Topotecan: 1 or 1.25 mg/m\^2 IV on Days 1 to 5, every 21 days or Vinorelbine: 30 mg/m\^2 IV on Days 1 and 8, every 21 days or Gemcitabine: 1000 mg/m\^2 IV on Days 1 and 8, every 21 days or Irinotecan: 100 or 125 mg/m\^2 IV weekly for 28 days, every 42 days or Pemetrexed: 500 mg/m\^2 IV on Day 1, every 21 days

Balstilimab (BAL)

Medical Director

This Phase 3 trial is an open-label, randomized study with single-agent Balstilimab (BAL) or Investigator Choice (IC) chemotherapy (single-agent gemcitabine, irinotecan, pemetrexed, vinorelbine, or topotecan) in patients with recurrent, persistent, or metastatic cervical cancer who have progressed after receiving platinum based chemotherapy.

The purpose of this Phase 3 trial is to demonstrate prolongation of OS in patients treated with BAL as compared to IC chemotherapy.

This Phase 3 trial is an open-label, randomized study with single-agent BAL or IC chemotherapy (single-agent gemcitabine, irinotecan, pemetrexed, vinorelbine, or topotecan) in patients with recurrent, persistent, or metastatic cervical cancer who have progressed after receiving platinum based chemotherapy.

Population:

Patients with recurrent, unresectable, or metastatic cervical cancer who have progressed after receiving at least 1 prior line of platinum-containing chemotherapy with or without bevacizumab.

In this study, \> 50% of patients will have received prior treatment with bevacizumab, which will be determined prior to enrollment.

Stratification

* Histology (squamous cell carcinoma \[SCC\] vs adenocarcinoma \[AC\] or adenosquamous carcinoma \[ASC\])
* Region of the world (United States or Europe Union or Australia vs other countries)
* Eastern Cooperative Oncology Group (ECOG) status 0 vs 1

Randomization

• 2:1, BAL: IC chemotherapy

Approximately 486 patients will be enrolled and randomized with 2:1 allocation between the BAL and IC chemotherapy arms.

Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer (BRAVA)

A Phase 3 Trial of Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer After Platinum-Based Chemotherapy (BRAVA)

Incidence of treatment-related TEAEs leading to death

Incidence of treatment-related TEAEs leading to treatment discontinuation

Median duration of treatment-related grade 3+ AEs

Area under BAL concentration-time curve, per dosing cycle

Anti-drug antibodies- incidence of anti-balstilimab antibodies including neutralizing antibodies.

Hazard Ratio for Overall Survival (OS) by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients with PD-L1 positive tumors

Hazard Ratio for OS by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients

Hazard Ratio for PFS by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients with PD-L1 positive tumors

Hazard Ratio for PFS by treatment assignment, stratified by histology, region of the world, ECOG PS in all patients

Proportion, with Wilson confidence intervals, of patients with best overall response (by RECIST 1.1) of PR or CR, among all patients with PD-L1 positive tumors randomized to BAL and to IC chemotherapy.

Proportion, with Wilson confidence intervals, of patients with best overall response (by RECIST 1.1) of PR or CR, among all patients randomized to BAL and to IC chemotherapy.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Phase 2a Immune Modulation With Ultrasound for Newly Diagnosed Glioblastoma	NCT05864534	Newly Diagnosed... Glioblastoma, I... Gliosarcoma Glioblastoma Mu...	Balstilimab Botensilimab Liposomal Doxor... Sonocloud-9 (SC...	18 Years -	Northwestern University
Balstilimab Versus Investigator Choice Chemotherapy in Patients With Recurrent Cervical Cancer (BRAVA)	NCT04943627	Advanced Cancer Metastatic Cerv...	Balstilimab (BA... Topotecan Vinorelbine Gemcitabine Irinotecan Pemetrexed	18 Years -	Agenus Inc.

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