P14.19.A PRE-CLINICAL SAFETY AND EFFICACY OF AN INNOVATIVE SURGICALLY IMPLANTABLE MEDICAL DEVICE TO DELIVER ELECTRIC FIELD THERAPY IN GLIOBLASTOMA

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Abstract BACKGROUND Glioblastoma (GBM) is the most common and aggressive primary brain cancer in adults. Current standard of care (SOC) involves maximal surgical resection and adjuvant chemoradiotherapy but clinical outcomes remain poor. Electric field therapy (EFT) is one of few developments in recent decades to demonstrate robust survival benefit in GBM, but is currently only available as an external system. Fully implantable EFT would allow continuous and immediate treatment following surgery thereby maximizing therapeutic efficacy. It would also preserve the quality of life of patients and caregivers. MATERIAL AND METHODS QV Bioelectronics (Manchester, UK) is developing a fully implantable system to deliver EFT in GBM, called GRACE. The first generation includes industry-standard, GBM-targeted electrodes, a custom cranioplasty for skull fixation, and an implantable pulse generator (IPG) to deliver proprietary stimulation regimes. Optimized stimulation regimes were applied to patient-derived 3D GBM cell lines (n=5) and human iPSC-derived neuronal cultures (n=4) to demonstrate treatment efficacy and selectivity. EFT was tested independently and alongside SOC options. Implanted EFT technology has progressed through formative usability and initial large animal studies. In silico modeling of GRACE was conducted to simulate electric field distributions around implanted electrodes and resultant heat dynamics in surrounding brain tissue with continuous device operation. RESULTS Proprietary stimulation regimes demonstrate at least 80% reduction in cancer cell viability across cell lines (L0627 p=0.0005, L160315 p=0.0020) - greater efficacy than currently used regimes described in the literature. Dosing compliance studies demonstrate the importance of continuous stimulation, with 2.7x greater reduction in cancer cell viability with 24hr/day stimulation vs. 18hr/day. Studies of EFT safety with neuronal cultures are underway with estimated completion later in 2024. QV Bioelectronics will also be undertaking further biological replicates with several patient-derived glioma stem cell lines. No gross abnormalities or adverse events related to EFT in pre-clinical health large animal models were noted. Initial in silico results demonstrate that therapeutically effective field strengths can be achieved in clinically relevant target volumes and can rapidly reach safe thermal equilibrium in continuous device operation. CONCLUSION QV Bioelectronics demonstrates novel, highly effective EFT regimes; studies to confirm GBM selectivity are underway. Simulation has demonstrated the feasibility of implantable EFT achieving therapeutic field strengths. Further work will combine optimized current delivery sequencing with MRI-derived GBM patient models to define a framework for clinical electrode trajectory planning.

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