P17.07.A SONOBIRD: A PHASE 3 TRIAL OF BBB OPENING WITH THE SONOCLOUD-9 IN RECURRENT GLIOBLASTOMA PATIENTS RECEIVING IV CARBOPLATIN

Abstract BACKGROUND This study aims to evaluate the efficacy of blood-brain barrier (BBB) disruption combined with chemotherapy in patients with first recurrence of glioblastoma through a randomized, comparative, multicenter Phase 3 pivotal trial. The trial is currently enrolling patients at 40 institutions across Europe and the United States (NCT05902169). A previous Phase 1/2 study (NCT03744026) demonstrated the safety and efficacy of BBB disruption using an implantable ultrasound system (SonoCloud-9, SC9) in recurrent glioblastoma treated with carboplatin (Carpentier et al., 2024). BBB disruption increased carboplatin concentrations by 5.9-fold (Sonabend et al., 2023). In optimally treated patients (n=12), median overall survival (mOS) was 14.0 months, with slower tumor growth observed. In the ongoing pivotal trial, eligible patients are randomized to either resection followed by SC9 implantation and ultrasound sonication with carboplatin (AUC 5, every 3 weeks), or resection followed by temozolomide or lomustine without BBB opening. The primary endpoint is overall survival. MATERIAL AND METHODS The SonoCloud-9 device, which contains nine 1-MHz, 10-mm diameter ultrasound emitters (Carthera, France), is implanted within the skull at the end of tumor resection. The device is activated in conjunction with intravenous DEFINITY® microbubbles (10 μl/kg, Lantheus, US) for 4.5 minutes at the time of each carboplatin infusion (AUC 5), administered every three weeks until disease progression or treatment completion, to transiently disrupt the BBB. In the control arm, patients receive either lomustine or temozolomide at the investigator’s discretion. Gadolinium-enhanced MRI (Gd-MRI) for disease assessment is performed every 2-3 months throughout the study. RESULTS As of the abstract submission date, over 100 patients have been enrolled. The first interim analysis is scheduled for June 2025. Safety and efficacy endpoints will be assessed at that time, with particular focus on progression-free survival (PFS), the first key secondary endpoint, and tumor growth rate. CONCLUSION Low-intensity pulsed ultrasound with microbubbles can transiently disrupt the BBB, enhancing chemotherapy delivery and potentially improving tumor control. Recruitment is ongoing and expected to be completed by the end of 2026. This trial is supported by Carthera.