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

  • Boudreau C
  • Najem H
  • Ott M
  • et al.
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Abstract

PURPOSE Activation of STING (Stimulator of INterferon Genes) can trigger a robust, innate anti-tumor immune response in immunologically "cold" tumors such as glioblastoma. EXPERIMENTAL DESIGN 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 (5µg - 20µg). Treatment was repeated every 4-6 weeks for a minimum of 2 cycles. Radiographic response to treatment was determined by response assessment in neuro-oncology criterion (RANO) criteria applied to isovoxel post-contrast T1-weighted MR images obtained on a single 3T magnet. RESULTS Six dogs were enrolled and completed {greater than or equal to}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 (PD), whereas there was 25% volumetric reduction in one subject and greater than >50% in the remaining surviving subjects. The median progression free survival (PFS) time was 14 weeks [range: 0 to 22 weeks], and the median overall survival (OS) time was 32 weeks [range: 11 to 39 weeks]. CONCLUSIONS Intratumoral STING agonist (IACS-8779) administration was well-tolerated in dogs with glioblastoma to a dose of 15µg. Higher doses of IACS-8779 were associated with radiographic responses.

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Boudreau, C. E., Najem, H., Ott, M., Horbinski, C., Fang, D., DeRay, C. M., … Heimberger, A. B. (2021). Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma. Clinical Cancer Research. https://doi.org/10.1158/1078-0432.ccr-21-1914

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