NCT05317858: LIMITLESS

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

Recruiting now Phase 3 Last updated 16 April 2026

What this trial tests

Phase 3 trial testing Blood Brain Barrier Opening - Oncology in Brain Tumor in 30 participants. Currently enrolling.

Timeline

12 August 2022

Primary endpoint
1 June 2027

1 December 2027

Quick facts

Lead sponsor	InSightec
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	single
Primary purpose	treatment
Enrollment	30
Start date	12 August 2022
Primary completion	1 June 2027
Estimated completion	1 December 2027
Sites	10 locations across Canada, United States, South Korea

Drugs / interventions tested

• Blood Brain Barrier Opening - Oncology
• Pembrolizumab (pembrolizumab) — full drug profile →
• Atezolizumab (atezolizumab) — full drug profile →
• Cemiplimab (CEMIPLIMAB) — full drug profile →
• Nivolumab (nivolumab) — full drug profile →
• Iptilimumab

Conditions studied

• Brain Tumor — all drugs for Brain Tumor →
• Non Small Cell Lung Cancer — all drugs for Non Small Cell Lung Cancer →

Sponsor

InSightec — full company profile →

Who can join

Adults 18 to 100, any sex, with Brain Tumor or Non Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Focused ultrasound-mediated enhancement of blood-brain barrier permeability for brain tumor treatment: a systematic review of clinical trials.
   Zhu H, Allwin C, Bassous MG, Pouliopoulos AN. · · 2024 · cited 34× · PMID 39207625 · DOI 10.1007/s11060-024-04795-z
2. Breaking Barriers in Neuro-Oncology: A Scoping Literature Review on Invasive and Non-Invasive Techniques for Blood-Brain Barrier Disruption.
   Pinkiewicz M, Pinkiewicz M, Walecki J, Zaczyński A, et al · · 2024 · cited 24× · PMID 38201663 · DOI 10.3390/cancers16010236
3. Consensus review on strategies to improve delivery across the blood-brain barrier including focused ultrasound.
   Piper K, Kumar JI, Domino J, Tuchek C, et al · · 2024 · cited 15× · PMID 38770775 · DOI 10.1093/neuonc/noae087
4. Exploring the Molecular Tumor Microenvironment and Translational Biomarkers in Brain Metastases of Non-Small-Cell Lung Cancer.
   Wen J, Yu JZ, Liu C, Ould Ismail AAO, et al · · 2024 · cited 13× · PMID 38396722 · DOI 10.3390/ijms25042044
5. Metastatic brain tumors: from development to cutting-edge treatment.
   Tanzhu G, Chen L, Ning J, Xue W, et al · · 2025 · cited 8× · PMID 39712454 · DOI 10.1002/mco2.70020
6. Fundamentals and Applications of Focused Ultrasound-Assisted Cancer Immune Checkpoint Inhibition for Solid Tumors.
   Jahangiri S, Yu F. · · 2024 · cited 7× · PMID 38543305 · DOI 10.3390/pharmaceutics16030411
7. Translational strategies and systems biology insights for blood-brain barrier opening and delivery in brain tumors and Alzheimer's disease.
   Song G, Plumlee P, Ahn JY, Wong ST, et al · · 2023 · cited 7× · PMID 37703663 · DOI 10.1016/j.biopha.2023.115450
8. Towards updated understanding of brain metastasis.
   Wang S, Feng Y, Chen L, Yu J, et al · · 2022 · cited 7× · PMID 36225632