Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma

Abstract

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 mg). 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 mg. Higher doses of IACS-8779 were associated with radiographic responses.