A Randomized Pivotal Study Assessing the Safety and Efficacy of Targeted Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound During the Standard of Care Treatment of Brain Metastases of Non-small Cell Lung Cancer (NSCLC) Origin

Plain English Summary

Blood-brain Barrier (BBB) Opening Using Exablate Focused Ultrasound With Standard of Care Treatment of NSCLC Brain Mets is a Phase 3 clinical trial sponsored by InSightec studying Brain Tumor, Non Small Cell Lung Cancer. This trial tests if using focused ultrasound to temporarily open the blood-brain barrier can help standard cancer treatments work better for lung cancer that has spread to the brain. It is for patients with non-small cell lung cancer that has spread to the brain and who are receiving specific immunotherapy treatments. Participation involves receiving focused ultrasound treatment along with standard immunotherapy, with regular check-ups and scans. Standard treatment for lung cancer with brain metastases typically involves radiation therapy, chemotherapy, or targeted therapies, and this trial explores an additional approach. The trial aims to enroll 30 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults 18 years and older with non-small cell lung cancer that has spread to the brain. Patients must be receiving specific immunotherapy drugs (immune checkpoint inhibitors) and have brain tumors that meet certain size criteria. Individuals with active brain bleeding, severe brain swelling, recent radiation to the brain, or certain other medical conditions may not be eligible. This trial is studying Brain Tumor, Non Small Cell Lung Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the focused ultrasound treatment is and whether it helps shrink or control the brain tumors, indicating if the new approach is beneficial. The specific primary outcome measures are: Adverse events (up to 6 months); tumor lesion(s) on the MRI images (up to 6 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a significant unmet need by exploring a novel way to enhance the effectiveness of existing immunotherapies for lung cancer that has spread to the brain, potentially improving outc As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Brain Tumor, Non Small Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This trial represents an investment in a novel therapeutic approach for a challenging cancer complication, with potential to expand the utility of existing immunotherapies and create a new market for Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if this trial is a good fit for you, especially regarding the focused ultrasound procedure and its potential benefits and risks. Participation will involve regular visits for treatment, monitoring for side effects, and imaging scans to assess tumor response. You will receive standard immunotherapy treatments, and the focused ultrasound will be administered on the same day as your infusions. This trial is currently recruiting participants. The trial is being conducted at 9 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: SINGLE
• Enrollment: 30 participants

Interventions

• DEVICE: 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.
• DRUG: Pembrolizumab — Pembrolizumab infusion
• DRUG: Atezolizumab — Atezolizumab infusion
• DRUG: Cemiplimab — Cemiplimab infusion
• DRUG: Nivolumab — Nivolumab infusion

Primary Outcomes

• Adverse events (up to 6 months)
• tumor lesion(s) on the MRI images (up to 6 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

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

Trial Locations

• St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States
• Miami Cancer Institute at Baptist Health, Miami, Florida, United States
• Moffitt Cancer Center, Tampa, Florida, United States
• University of Maryland, Baltimore, Maryland, United States
• Atrium Health Wake Forest Baptist, Winston-Salem, North Carolina, United States
• Rhode Island Hospital, Providence, Rhode Island, United States
• Johnston Willis Hospital, Richmond, Virginia, United States
• Sunnybrook Research Institute, Toronto, Ontario, Canada
• Samsung Medical Center, Seoul, Seoul, South Korea

Frequently Asked Questions

Related Conditions

• Lung Cancer
• Brain Metastases
• Non-Small Cell Lung Cancer
• Brain Tumors
• Cancer Therapy
• Immunotherapy
• Focused Ultrasound
• Blood-Brain Barrier
• Oncology
• Neurology

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