# STINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBM

> **NIH NIH P50** · NORTHWESTERN UNIVERSITY · 2023 · $285,775

## Abstract

PROJECT 2: SUMMARY
The glioblastoma (GBM) microenvironment is dominated by myeloid cell infiltrates. Results from multiple studies
indicate these tumor-associated myeloid cells (TAMS) as supporting GBM growth. The goal of this project is to
reprogram TAMS for immunologic anti-tumor activity. Stimulator of interferon genes (STING) is a widely expressed
sensor of cellular stress that is activated by the presence of DNA in the cytoplasm. Distinct from most other immune
agonists, STING activation re-educates tumor supportive M2 macrophage TAMS toward a proinflammatory anti-
tumor M1 phenotype. Macrophage proinflammatory phenotypic conversion, in turn, promotes cytotoxic T cell
infiltration of and activity against tumor. We have developed a high potency STING agonist, IACS-8803, with
marked antitumor activity when tested in humanized mice bearing human GBM, and in canines with
spontaneously arising high-grade gliomas. In addressing the clinical potential of this agonist in treating GBM, we
will first determine its effect on interferon responses, using [18F]FLT PET, when IACS-8803 is administered to
patients with recurrent tumor. This first-in-man Phase I clinical trial will inform regarding the range in IACS-8803
activity that is observed across the cohort of treated patients, with activity results compared against tumor
molecular characteristics, and patient clinical data. The clinical trial will include analysis of several unique
endpoints, among which are target engagement and longitudinal kinetics of IACS-8803 induced T cell chemokine
expression such as CXCL10. In addition, a window-of-opportunity patient cohort will receive direct intratumoral
administration of IACS-8803, and whose results will be compared against those from patients that have received
systemic administration of standard-of-care therapeutics. The PET Imaging results will be analyzed with respect
to inflammatory immune response in resected tumors from active vs. non-active tracer regions in post-STING
treated subjects, using multiplex immunofluorescence, CyTOF, and/or mass cytometry. This clinical study will
ultimately provide sufficient data to make a clear go/no go determination for later-stage clinical trials based on
sufficient target engagement in the tumor microenvironment. While conducting this clinical trial, we will move
forward with preclinical research by evaluating the efficacy of combined IAC-8803 + radiation in orthotopic
models of GBM. Results from these preclinical studies will inform whether STING agonist and radiation treatment
should be tested in patients with newly diagnosed GBM, and whose tumors have unmethylated MGMT promoter,
and as such, do not require treatment with temozolomide.

## Key facts

- **NIH application ID:** 10626394
- **Project number:** 2P50CA221747-06
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Amy Beth Heimberger
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $285,775
- **Award type:** 2
- **Project period:** 2018-08-17 → 2028-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10626394

## Citation

> US National Institutes of Health, RePORTER application 10626394, STINGing GBM: A First-in- Man Clinical Trial in Surgical Resectable Recurrent GBM (2P50CA221747-06). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10626394. Licensed CC0.

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