Lung Cancer Brain Metastases: Multisite Focused Ultrasound and Immunotherapy Trial Begins


Key Points

  • Five sites across the US and Canada have begun a clinical trial to investigate focused ultrasound’s role in enhancing immunotherapy for non-small cell lung cancer that has spread to the brain.
  • Researchers predict that using focused ultrasound to open the blood-brain barrier will enable higher concentrations of the immunotherapy drug to enter the brain tumor tissue.
  • Participants will be monitored to assess whether the therapy helps activate the immune system to destroy the tumor.

Update: In October 2023, HCA Healthcare’s Johnston-Willis Hospital in Richmond, Virginia, announced clinicians there had treated the first two patients in this clinical trial. Read the Press Release.

A multisite pivotal clinical trial using focused ultrasound in combination with an immunotherapy drug to treat non-small cell lung cancer (NSCLC) that has spread to the brain has begun at four sites across the US and Canada.

The trial is investigating the use of Insightec’s Exablate Neuro focused ultrasound device to open the blood-brain barrier (BBB) in combination with the immunotherapy drug pembrolizumab – commonly known as Keytruda® – in participants with brain metastases from NSCLC. The focused ultrasound is delivered with circulating microbubbles, otherwise known as ‘ultrasound contrast agents’ in radiology uses. The microbubbles oscillate within the ultrasound field and can disrupt the BBB.

The BBB is composed of neurovascular units that create a protective layer of tightly joined cells that prevents harmful substances, such as toxins and infectious agents, from diffusing into the surrounding brain tissue. It can also prevent beneficial therapeutic agents from getting into the brain, which is why research has centered on using focused ultrasound to safely and temporarily open the BBB.

Researchers predict that temporarily disrupting the BBB in and around the tumor will enable higher concentrations of pembrolizumab to enter this targeted region and activate the immune system to destroy the tumor.

We recently spoke with Graeme Woodworth, MD, professor of neurosurgery and director of the Brain Tumor Treatment & Research Center at the University of Maryland School of Medicine, about the trial.

The randomized trial will enroll 20 participants into two cohorts. One group will only receive pembrolizumab, the current standard-of-care therapy. The other group will receive focused ultrasound in addition to pembrolizumab. Researchers will evaluate whether the BBB disruption enables higher concentrations of the drug to enter the brain tumor.

NSCLC is the most common cause of brain metastases. The challenges in treating the disease are two-fold: most promising therapeutics cannot pass through the BBB in high enough concentrations, and these tumors often grow near important areas that control crucial body functions.

“At diagnosis, 20-25% of stage IV lung cancer patients have brain metastases, and more than half of patients develop them if they survive longer than two years,” said Manmeet Ahluwalia, MD, MBA, chief of medical oncology at Miami Cancer Institute at Baptist Health and principal investigator for this trial. “BBB disruption with low frequency ultrasound presents an intriguing opportunity to augment the responses seen with immunotherapy and chemotherapy in the brain.” 

Also leading the trial are Nir Lipsman, MD, PhD, at Sunnybrook Health Sciences Centre, Nader Sanai, MD, at the Ivy Brain Tumor Center in Phoenix, Arizona, and Graeme Woodworth, MD, at the University of Maryland, Baltimore. The trial is being sponsored by Insightec.

Learn More About This Study
Listen to Dr. Woodworth Describe the Study

For Patients

If you are interested in speaking to someone about this trial, please contact one of the sites below.

St. Joseph’s Hospital and Medical Center
Phoenix, Arizona, USA
Contact: 602-406-8605 or

Miami Cancer Institute at Baptist Health
Miami, Florida, USA
Contact: Daylan L Santana, RN at 786-527-8528 or  
Contact: Juliana Montoya at 786-527-8864 or

University of Maryland
Baltimore, Maryland, USA
Contact: Kaitlyn Henry at 410-328-0939 or  
Contact: Charlie Klontz at 410-328-5332 or  

Johnston Willis Hospital
Richmond, Virginia
Contact: Kanwalcharan S Sahni, MD, at 804-330-4990 or

Sunnybrook Research Institute
Toronto, Ontario, Canada
Contact: Meheleth Llinas at 416-480-6100 ext. 2476 or