September 18, 2017 — Theraclion and co-lead investigator David Brenin, M.D., from the University of Virginia School of Medicine, recently discussed the rationale and design of the first clinical trial combining Theraclion’s Echotherapy with the checkpoint inhibitor pembrolizumab in women with metastatic breast cancer.
Breast cancer is one of the most common malignancies with approximately 250,000 new cases expected in the U.S. in 2017. One in eight women will be diagnosed with breast cancer in their lifetimes. It is the second leading cause of death from cancer with approximately 40,000 annual deaths. Although diagnosis, treatment and survival has improved, advanced stage IV metastatic disease remains a significant challenge, with no curative therapies and a 22 percent five-year survival rate. Although immune-oncology approaches have revolutionized treatment for several cancers, such as lung cancer and melanoma, breast cancer has been resistant to immune-oncology approaches, according to Brenin, chief of breast surgery at UVA School of Medicine. The immune system does not mount an immune response against most breast cancers as tumor cells are not recognized as foreign.
Brenin’s key points included:
- Echotherapy, also known as high intensity focused ultrasound (HIFU), induced localized tissue heating and disruption at the treatment focal point, with minimum impact on surrounding structures. Studies demonstrate that it is very well tolerated and efficacious in non-invasively removing lesions;
- Studies have demonstrated that HIFU treatment induces an immune system response with significant increases in immune cells;
- Pembrolizumab is able to induce an immune response to some breast cancers and HIFU is able to induce an immune response in most tumors, but not enough on its own to be curative. The rationale for the clinical study is that the combination might be more effective. HIFU facilitates infiltration of T-cells and Pembrolizumab blocks PD-1 receptors on cytotoxic T-cells greatly up-regulating the T-cell response to the breast cancer cells;
- The clinical trial is expected to begin patient accrual at UVA in October 2017, and will be a two-arm study of 12 patients. Patients in Arm A will be treated with pembrolizumab first followed by HIFU treatment; Arm B will be the reverse. Primary objectives are to assess the adverse event profile of pembrolizumab and focused ultrasound therapy in patients with metastatic breast cancer, and to determine whether the addition of pembrolizumab to focused ultrasound increases the proportion of CD8+ tumor infiltrating lymphocytes (ratio CD8+/CD4+) in the primary ablation zone; and
- Secondary objectives are to compare CD8+ T-cell responses at peri-ablation zones when pembrolizumab is given before or after HIFU, to evaluate clinical responses at local and distant metastatic sites by CT (computed tomography) scan and to evaluate progression free and overall survival.
For more information: www.theraclion.com
January 20, 2026 
