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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 5528-5535 |
| Number of pages | 8 |
| Journal | Clinical Cancer Research |
| Volume | 27 |
| Issue number | 20 |
| DOIs | |
| State | Published - Oct 15 2021 |
Funding
The study was designed by the investigators, who oversaw all data collection and interpretations. The funding agencies, including the NIH R01 NS120547, the Joan Traver Walsh Family Foundation, the Dr. Marnie Rose Foundation, the Brockman Foundation, and Mr. Herb Simmons, had no role in the data analysis, interpretation of the results, or writing of the article. C. Horbinski reports grants from NIH during the conduct of the study. M.A. Curran reports grants and personal fees from ImmunoGenesis, Inc., ImmunoMet, Inc., as well as personal fees from Agenus, Inc., Alligator Bioscience, Inc., ImmunOs, Inc., Oncor-esponse, Inc., Pieris, Inc., Nurix, Inc., Aptevo, Inc., Servier, Inc., Kineta, Inc., Salarius, Inc., Xencor, Inc., Amunix, Inc., Mereo, Inc., and Adagene, Inc. outside the submitted work. In addition, M.A. Curran has a patent for Methods and Composition for Localized Secretion of Anti-CTLA-4 Antibodies issued, licensed, and with royalties paid from multiple licensees; a patent for Dual Specificity Antibodies Which Bind Both PD-L1 and PD-L2 and Prevent Their Binding to PD-1 issued, licensed, and with royalties paid from ImmunoGenesis, Inc.; and a patent for Cyclic Dinucleotides as Agonists of Stimulator of Interferon Gene Dependent Signaling issued and licensed. A.B. Heimberger reports grants from NIH, Joan Traver Walsh Family Foundation, Dr.Marie Rose Foundation, Brockman Foundation, and Mr. Herb Simmons during the conduct of the study. A.B. Heimberger also reports personal fees from Caris Life Science and WCG Oncology; other support from Celldex Therapeutics, DNAtrix, Carthera, and Moleculin; and grants from Celularity and Codiak outside the submitted work. No disclosures were reported by the other authors.
ASJC Scopus subject areas
- General Medicine
