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

Posted on 2024-10-30 - 21:00
AbstractPurpose:

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

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Joan Traver Walsh Family Foundation

Dr. Marnie Rose Foundation

Brockman Foundation

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AUTHORS (9)

C. Elizabeth Boudreau
Hinda Najem
Martina Ott
Craig Horbinski
Dexing Fang
Chase M. DeRay
Jonathan M. Levine
Michael A. Curran
Amy B. Heimberger
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