Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma.
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PURPOSE: Activation of STING (stimulator of interferon genes) can trigger a robust, innate antitumor immune response in immunologically "cold" tumors such as glioblastoma. PATIENTS AND METHODS: A small-molecule STING agonist, IACS-8779, was stereotactically administered using intraoperative navigation intratumorally in dogs with spontaneously arising glioblastoma. The phase I trial used an escalating dose design, ascending through four dose levels (5-20 g). Treatment was repeated every 4-6 weeks for a minimum of two cycles. Radiographic response to treatment was determined by response assessment in neuro-oncology (RANO) criteria applied to isovoxel postcontrast T1-weighted MR images obtained on a single 3T magnet. RESULTS: Six dogs were enrolled and completed 1 cycle of treatment. One dog was determined to have an abscess and was removed from further analysis. One procedure-related fatality was observed. Radiographic responses were dose dependent after the first cycle. The first subject had progressive disease, whereas there was 25% volumetric reduction in one subject and greater than 50% in the remaining surviving subjects. The median progression-free survival time was 14 weeks (range: 0-22 weeks), and the median overall survival time was 32 weeks (range: 11-39 weeks). CONCLUSIONS: Intratumoral STING agonist (IACS-8779) administration was well tolerated in dogs with glioblastoma to a dose of 15 g. Higher doses of IACS-8779 were associated with radiographic responses.