# A Phase II Clinical Trial in Newly Diagnosed Glioblastoma Patients Treated with WP1066 and Radiation

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2024 · $568,219

## Abstract

SUMMARY
The brain tumor microenvironment (TME) is dominated by myeloid cell infiltrates which are mostly brain resident
microglia and infiltrating glioblastoma-associated myeloid cells (GAMs). Despite this fact, most clinical trials for
glioblastoma have been directed to T cell-based immunotherapies, which have failed to impact outcome for most
patients. Targeting glioblastoma based on re-education of GAMS to enable immunological clearance is the goal
of this clinical trial. The signal transducer and activator of transcription 3 (STAT3) is a negative regulator of both
innate and adaptive immunity and this pathway is markedly up regulated in the TME. We have previously
developed and tested, in the context of Phase I clinical trials, a first-in-man blood-brain-barrier penetrant small
molecule inhibitor of STAT3, designated WP1066. The Phase I trial results have shown that WP1066 is well
tolerated and is inhibiting the STAT3 target in immune cells. As a monotherapy, WP1066 treatment has
demonstrated the ability to stimulate robust anti-tumor response in multiple preclinical studies that is further
enhanced with radiation therapy, which is standard of care for newly diagnosed glioblastoma and is known to
increase tumor immunogenicity. Unbiased nanostring analysis of treated tumors revealed that activation of
antigen presentation in the TME with the combination treatment. For the research proposed here we want to
extend our preclinical findings to newly diagnosed glioblastoma patients. In this clinical trial, we will test the
hypothesis that the administration of WP1066 with radiation will induce T cell-dendritic cell cluster interactions in
the glioblastoma microenvironment, and this induction, in turn, will increase progression free survival (PFS) for
glioblastoma patients. In specific Aim 1, we conduct a Phase II trial with an expansion cohort for the combination
of WP1066 and radiation in newly diagnosed MGMT unmethylated glioblastoma patients. In cohort 1, newly
diagnosed MGMT unmethylated, IDH1 wild-type glioblastoma patients will be treated with 8 mg/kg of WP1066
while undergoing standard-of-care radiation therapy at a daily dose of 2 Gy. PFS will be used to ascertain if there
is indication of treatment benefit. In cohort 2, patients for whom gross total resection was not achieved will be
treated with the combination of radiation and WP1066 with the intent of obtaining treated tumor, if a surgically
amenable lesion is present. Such tissue would allow for analysis of TME immune activation and cluster
interactions, drug concentrations and target engagement in Aim 2. Aim 2 will also use longitudinal textural MRI
analysis to correlate inflammatory responses in the TME by using our STAT3-specific multiplex immune
fluorescent panel and complementary ex vivo flow cytometry and nanostring profiling. STAT3 target inhibition,
including within specific immune cell populations, will be ascertained through use of the multiplex panel, which
will also inform ...

## Key facts

- **NIH application ID:** 10837735
- **Project number:** 5R01CA272639-02
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Amy Beth Heimberger
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $568,219
- **Award type:** 5
- **Project period:** 2023-05-05 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10837735

## Citation

> US National Institutes of Health, RePORTER application 10837735, A Phase II Clinical Trial in Newly Diagnosed Glioblastoma Patients Treated with WP1066 and Radiation (5R01CA272639-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10837735. Licensed CC0.

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