Recruiting
Phase 3

Exablate with NSCLC

Sponsor:

InSightec

Code:

NCT05317858

Conditions

Brain Tumor

Non Small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Blood Brain Barrier Opening - Oncology

Pembrolizumab

Atezolizumab

Cemiplimab

Nivolumab

Study Details

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

Study ID

NCT05317858

Start date

Aug 12, 2022

Status verified date

Aug, 2026

Completion date

Dec 1, 2027

Anticipated

Primary completion date

Jun 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria

  • 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.
  • Has a diagnosis of active autoimmune disease (e.g., autoimmune Hepatitis, Guillain-Barre Syndrome, etc.) requiring systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. History of (non-infectious) pneumonitis that requires steroids or has current pneumonitis
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Subject is currently enrolled in another intervention based clinical trial

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: ICI Systemic Therapy with Exablate BBBO

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

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

subjects will undergo planned on-label ICI Systemic Therapy.

Interventions

Blood Brain Barrier Opening - Oncology

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

Pembrolizumab

Pembrolizumab infusion

Atezolizumab

Atezolizumab infusion

Cemiplimab

Cemiplimab infusion

Nivolumab

Nivolumab infusion

Iptilimumab

Iptilimumab infusion

Primary outcome measure

  • Adverse events [ Time Frame: up to 6 months ]
  • tumor lesion(s) on the MRI images [ Time Frame: up to 6 months ]

Central Contacts and Locations

Central contacts

Alyssa Voelker-Christy

817-948-5219clinicalresearchquestions@insightec.com

Locations

Hoag Memorial Hospital Presbyterian

Recruiting

Newport Beach, California, United States, 92663

Contacts

Simon Khagi, MD, MBA, FACP

949-764-4060Simon.Khagi@hoag.org

Julie Nguyen

(949) 764-6271Julie.Nguyen@hoag.org

Broward Health

Recruiting

Fort Lauderdale, Florida, United States, 33316

Contacts

Shirley Cheraime, RN, BSN

954.712.3904scheraime@browardhealth.org

Simone Dockery Franklin

Sfranklin@browardhealth.org

Principal Investigator:

Shaye Moskowitz, MD

Miami Cancer Institute at Baptist Health

Recruiting

Miami, Florida, United States, 33176

Contacts

Natalie Brunelle

786-533-9460Natalie.Brunelle@Baptisthealth.net

Principal Investigator:

Manmeet S Ahluwalia, MD

Moffitt Cancer Center

Recruiting

Tampa, Florida, United States, 33612

Contacts

Carie Bliss

(813) 745-2131Carie.Bliss@moffitt.org

Principal Investigator:

Yolanda Pina, Neuro-Oncology

University of Maryland

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Kaitlyn Henry

410-328-0939KHenry@som.umaryland.edu

Rayne Noyes

410-328-5332anoyes@som.umaryland.edu

Principal Investigator:

Graeme Woodworth, MD

Atrium Health Wake Forest Baptist

Recruiting

Winston-Salem, North Carolina, United States, 27103

Contacts

Adrian Laxton, BA, MA, MD, FRCSC, FAANS

336-716-6438Adrian.Laxton@wfusm.edu

Wendy Jenkins, RN, BSN

336-716-3842Wendy.Jenkins@Advocatehealth.org

Principal Investigator:

Adrian Laxton, BA, MA, MD, FRCSC, FAANS

Oregon Health & Science University

Recruiting

Portland, Oregon, United States, 97239

Contacts

Michael McGehee, MS

971-509-4932nsgclinicalresearch@ohsu.edu

Principal Investigator:

Ahmed Raslan, MBBCh, MSc, MD, FAANS

Rhode Island Hospital

Recruiting

Providence, Rhode Island, United States, 02903

Contacts

Maria Duffy

(401) 444-2243mduffy@brownhealth.org

Owen Leary

(401) 606-8388owen.leary@brownhealth.org

Principal Investigator:

Clark Chen

More Information

Sponsor

InSightec

Last update posted

Aug 19, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by InSightec on 2026-08-19.