TMOD-04. SAFETY AND EFFICACY DATA FROM A CLINICAL TRIAL OF SONODYNAMIC THERAPY WITH 5-ALA HCL ORAL SOLUTION AND CV-01 DELIVERED WHOLE HEMISPHERIC LOW-INTENSITY NON-ABLATIVE ULTRASOUND IN PET FRENCH BULLDOGS WITH<i>DE NOVO</i> NATURALLY OCCURRING HIGH

Abstract To date, no animal model has been able to accurately test emerging therapeutics for high-grade glioma. Pet dogs’ high-grade gliomas closely mimic human tumors histopathologically and radiologically as well as with poor clinical survival. Dogs with these tumors have notably shorter survival than humans, with French Bulldogs showing the shortest survival of all breeds affected, aiding swift therapeutic evaluations. We report the first use of the novel CV-01 device delivering non-ablative low-intensity diffuse ultrasound (LIDU) with oral 5-ALA as a recurrent high-grade glioma treatment in a veterinary safety and efficacy trial. This Phase 1 study focused on safety, with secondary outcomes assessing histopathological efficacy markers (CC3, Iba1) and overall survival. After one SDT treatment pre-resection, treatments every 3-4 weeks were administered to eight French Bulldogs, totaling 60 administrations (average of 7.5 total treatments/patient). The control group matched breed, age, and histopathologic diagnosis. Average age was 6.35 years (range: 4.8 – 7.8 years), slightly older than controls (5.9 years, range: 3.0 - 9.9 years). No complications or toxicities were noted, and MRI scans showed no damage to the normal brain. Histopathologic analysis from four canine tumor samples revealed increased apoptosis and immune activation markers post-SDT (e.g. cleaved caspase 3 [CC3] and ionized calcium-binding adaptor molecule 1 [Iba1]), indicating selective tumor cell death. Median overall survival in the treatment group reached 205.5 days (6.8 months) compared to 55 days (1.8 months) in controls, with the longest survival at 587 days (versus 213 in controls). Although preliminary, these results affirm the safety of 5-ALA-mediated SDT in canine glioma patients. A multi-center, First-In-Human trial in recurrent high-grade glioma recently completed enrollment, aiming to further validate canine trials for emerging high-grade glioma therapeutics.