CTNI-37. SONOBIRD: A PHASE 3 TRIAL OF BLOOD-BRAIN-BARRIER (BBB) OPENING WITH THE SONOCLOUD-9 IN RECURRENT GLIOBLASTOMA PATIENTS RECEIVING IV CARBOPLATIN

Abstract This study aims to determine the efficacy of BBB disruption combined with carboplatin chemotherapy for patients with first recurrence of glioblastoma through a randomized, comparative, multicenter, phase 3 trial. The trial is open for enrollment at 40 institutions throughout Europe and the United States (NCT05902169). A prior Phase 1/2 study (NCT03744026) showed the safety and efficacy of BBB disruption using an implantable ultrasound system (SC9) in recurrent glioblastoma with carboplatin (Carpentier et al. Nature Comm 2024). BBB disruption increased carboplatin concentrations 5.9-fold (Sonabend et al, 2023), and led to trapping of carboplatin in the human brain interstitium over 24 hours (Habashy et al., Clin Cancer Res 2025). In optimally treated patients (n=12), mOS was 14.0 months, with slower tumor growth. The ongoing pivotal trial randomizes patients who are amenable to tumor resection to either resection with SC9 implantation followed by sonication + carboplatin (AUC 5 q3 weeks) or resection followed by temozolomide or lomustine without BBB opening. The primary endpoint is overall survival. At the end of surgery, the SonoCloud-9 device, containing nine, 1-MHz, 10-mm diameter ultrasound emitters (Carthera, France) is placed. Approx, 2-3 weeks later, the device is activated for 4 ½ minutes while microbubbles (Definity®, Lantheus; 10 ul/kg) are intravenously administered to disrupt the BBB just after i.v. carboplatin (AUC 5) is infused over 30 minutes. This procedure will be repeated every 3 weeks up to 7 cycles. In the control arm, patients receive either lomustine or temozolomide at investigator’s discretion. Gd-MRI for disease evaluation is performed every 2-3 months for the duration of the study. As of May 2025, 130/560 patients have been included. The ongoing pivotal trial is recruiting and estimated to complete enrollment by the end of 2026. This trial is supported by Carthera.