Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound With Standard of Care Treatment of NSCLC Brain Mets

NCT05317858 | Recruiting Phase 3 DMC FDA Drug FDA Device

• 1 other identifier: BT012
• Study Type: interventional
• Target: 30
• Locations: 3 countries
• Sites: 10

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of targeted blood brain barrier opening with Exablate Model 4000 Type 2.0/2.1 for the treatment of NSCLC brain metastases in patients who are undergoing planned FDA approved, on-label systemic therapy utilizing immune checkpoint inhibitors.

Conditions

Brain Tumor; Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (2)

• Adverse events

  Adverse events \[ Time Frame: Through study completion, up to 6 months\]. All adverse events and/or Serious Adverse Events will be documented and reported according to CTCAE criteria.

  up to 6 months

• tumor lesion(s) on the MRI images

  Efficacy will be determined by the response of the tumor lesion(s) compared to baseline. Tumor lesions on the MRI images (units: mm) will be measured every three weeks up to six months.

  up to 6 months

Secondary Outcomes (2)

• evaluation of Neuro Oncology Brain Mets (RANO-BM) response

  up to 6 months

• Time to response for brain metastases by treatment arm [applicable to the completed stage 1a only]

  up to 6 months

Other Outcomes (2)

• Patient reported quality of life measurement questionnaires

  up to 6 months

• Measurement of BBB Opening

  up to 6 months

Study Arms (2)

ICI Systemic Therapy with Exablate BBBO

EXPERIMENTAL

Using Exablate Model 4000 Type 2 for the treatment of NSCLC brain metastases in subjects who are undergoing planned ICI Systemic Therapy.

Device: Blood Brain Barrier Opening - Oncology; Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Cemiplimab; Drug: Nivolumab; Drug: Iptilimumab

Control Arm (ICI Systemic Therapy on-label use only)

ACTIVE COMPARATOR

subjects will undergo planned on-label ICI Systemic Therapy.

Drug: Pembrolizumab; Drug: Atezolizumab; Drug: Cemiplimab; Drug: Nivolumab; Drug: Iptilimumab

Interventions

Blood Brain Barrier Opening - Oncology DEVICE

BBB opening via Exablate Type 2 system with microbubble resonators on the day of ICI infusion to treat brain metastases.

Also known as: Exablate BBBO

ICI Systemic Therapy with Exablate BBBO

Pembrolizumab DRUG

Pembrolizumab infusion

Also known as: KEYTRUDA

Control Arm (ICI Systemic Therapy on-label use only); ICI Systemic Therapy with Exablate BBBO

Atezolizumab DRUG

Atezolizumab infusion

Also known as: Tecentriq

Control Arm (ICI Systemic Therapy on-label use only); ICI Systemic Therapy with Exablate BBBO

Cemiplimab DRUG

Cemiplimab infusion

Also known as: LIBTAYO

Control Arm (ICI Systemic Therapy on-label use only); ICI Systemic Therapy with Exablate BBBO

Nivolumab DRUG

Nivolumab infusion

Control Arm (ICI Systemic Therapy on-label use only); ICI Systemic Therapy with Exablate BBBO

Iptilimumab DRUG

Iptilimumab infusion

Control Arm (ICI Systemic Therapy on-label use only); ICI Systemic Therapy with Exablate BBBO

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant is ≥ 18 years of age
• The participant provides written informed consent for the trial
• Participant is willing to comply with all study procedures for the duration of the study
• Participant has a Karnofsky Performance Status ≥ 70% and/or ECOG 0-2
• Participant is a NSCLC subject prescribed immune checkpoint inhibitor systemic therapy according to on-label use with the target brain lesion(s) measuring ≥ 0.5 cm in longest diameter. Target mets may include: De novo mets for which surgery and radiation can be deferred, Mets with or without history of prior radiation, Mets with history of radiation after at least 8 weeks since last radiation treatment, and In the event a previously treated met has progressed according to institutional practice within 4 weeks post radiation treatment, the met may be study eligible, and/or if in the opinion of the Investigator, the subject may benefit from the study procedure.
• Female subject is not planning pregnancy during the study duration and confirmed NOT PREGNANT each procedure day.
• Screening/Baseline laboratory values Screening/Baseline should adhere to local standard of care lab values for ICI therapy

You may not qualify if:

• Participant has evidence of acute intracranial hemorrhage
• Participant at risk for spontaneous intracranial hemorrhage (e.g., history of metastatic melanoma or other tissue histology).
• Participant has signs and symptoms of increased intracranial pressure or symptomatic mass effect, midline shift or evidence of subfalcine, uncal or tonsillar herniation.
• Participant receiving Bevacizumab (Avastin) therapy, or other drugs with a proclivity for causing bleeding.
• History of bleeding disorders or tissue pathologies which increase the subject's risk of hemorrhage for anticoagulation medications, implement pre-surgical standard procedure to avoid increased risk of a bleeding event.
• Participant has an infectious viral infection such as active Hepatitis B, Hepatitis C or detectable HIV viral load or participants with active bacterial infection such as TB (Bacillus tuberculosis) that may, in the opinion of the investigator, interfere with the subject receiving the study therapy or procedures or otherwise impact their participation in the trial.
• Subjects with evidence of cranial or systemic infection.
• Participant has received a solid organ or hematopoietic stem cell transplant.
• Participant has received a live vaccine within 28 days prior to the first on-study ICI infusion with or without Exablate.
• Known sensitivity to DEFINITY® ultrasound contrast agent or hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol, as found in MiraLAX and bowel prep products.
• Contraindications to MRI and gadolinium-DTPA including non-MRI-compatible implanted devices, severe claustrophobia, unable to lie supine in MRI.
• Subjects with significant liver dysfunction, (cirrhosis, hemochromatosis, severe alcohol abuse, or active hepatitis (autoimmune or infectious))
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first on-study ICI infusion with or without Exablate. Note: prophylactic steroid use for ICI and chemotherapy infusion per institutional practice is allowed per protocol.
• Has a known additional malignancy that requires active treatment that would interfere with study procedures.
• Known presence of leptomeningeal disease.

Sponsors & Collaborators

• InSightec: lead

Study Sites (10)

St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

NOT YET RECRUITING

Miami Cancer Institute at Baptist Health

Miami, Florida, 33176, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

University of Maryland

Baltimore, Maryland, 21201, United States

RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27103, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Johnston Willis Hospital

Richmond, Virginia, 23235, United States

RECRUITING

Sunnybrook Research Institute

Toronto, Ontario, M4N 3M5, Canada

COMPLETED

Samsung Medical Center

Seoul, Seoul, 06351, South Korea

NOT YET RECRUITING

MeSH Terms

Conditions

Brain Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

pembrolizumab; atezolizumab; cemiplimab; Nivolumab

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Manmeet Ahluwalia, MD, MBA

  Miami Cancer Institute, Baptist Health South Florida

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alyssa Voelker-Christy

CONTACT

817-948-5219; clinicalresearchquestions@insightec.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Imaging Core Lab is Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: April 8, 2022
• Study Start: August 12, 2022
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 16, 2026

Record last verified: 2026-04

Locations

KR (1); US (8); CA (1)