Intratumoral Delivery of STING Agonist Results in Clinical Responses in Canine Glioblastoma | Academic Article individual record
abstract

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 (520 g). Treatment was repeated every 46 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: 022 weeks), and the median overall survival time was 32 weeks (range: 1139 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.

publication outlet

Clinical Cancer Research

author list (cited authors)
Boudreau, C. E., Najem, H., Ott, M., Horbinski, C., Fang, D., DeRay, C. M., ... Heimberger, A. B.
publication date
2021
keywords
  • Interferons
  • Neurosciences
  • Dogs
  • Clinical Trials And Supportive Activities
  • Injections, Intralesional
  • Treatment Outcome
  • Brain Cancer
  • Animals
  • Glioblastoma
  • Brain Neoplasms
  • Cancer
  • Biomedical Imaging
  • Female
  • Rare Diseases
  • Brain Disorders
  • Clinical Research