Multicenter phase 1-2 trial of microbubble-enhanced transcranial focused ultrasound wiith temozolomide for high-grade glioma

Brain-infiltrating tumor cells from high-grade glioma remain shielded from drug treatments by the blood-brain barrier. Microbubble-enhanced transcranial focused ultrasound (MB-FUS) enables controlled blood-brain barrier opening (BBBO), permitting localized drug delivery. The phase 1-2 BT008NA trial, at five sites in the USA and Canada, evaluated MB-FUS plus standard-of-care temozolomide for individuals with high-grade glioma. The trial included 34 participants (mean age 51.5 ± 13.0 years; median follow-up 44.5 months). Two of 176 adverse events (1%) were grade 5 (disease-related deaths), three (2%) grade 4 (temozolomide-related hematological abnormalities), and eight (5%) grade 3 (one MB-FUS related); these occurred across seven (21%) of 34 participants). Median overall survival was 31.3 months (95% CI 21.1-NR) and median progression-free survival was 13.5 months (9.9-26.9). The authors conclude that MB-FUS plus temozolomide is a safe combinatorial therapeutic approach for individuals with high-grade glioma.