# Chemo-radio immunotherapy for pediatric brain tumors

> **NIH NIH R01** · AUGUSTA UNIVERSITY · 2021 · $581,700

## Abstract

Brain tumors are the most common solid tumor of childhood. Some can be cured, but for the 30-35% of pediatric
patients who recur following front-line therapy – and for every child with diffuse intrinsic pontine glioma (DIPG) –
there is essentially no chance of cure with standard treatment. Thus, more effective therapies are urgently
needed. The scientific premise underlying the current proposal is that conventional radiation and
chemotherapy release large amounts of antigen from dying tumor cells, but that this normally cannot trigger a
useful immune response because immunogenic antigen-presentation is suppressed by tumor-induced
mechanisms such as the indoleamine 2,3-dioxygenase (IDO) pathway, a natural mechanism that profoundly
inhibits immune response to apoptotic cells. The proposal hypothesizes that adding immunologic therapy using
indoximod, an oral inhibitor of the IDO pathway, in combination with radiation and chemotherapy, will allow
prolonged survival in these otherwise refractory patients. The applicants have recently completed a first-in-
pediatrics Phase 1 study of the proposed indoximod-based chemo-radio-immunotherapy approach in 53 children
with recurrent brain tumors. This proof-of-concept study shows a median Overall Survival of 17.2 months, which
is markedly superior to historical comparator studies, with low toxicity.
 Aim 1 will conduct a Phase 2, stratified-design trial of indoximod immunotherapy in combination with
 temozolomide (TMZ) chemotherapy, with or without the addition of novel Low-Dose Partial-field (LDPF)
 radiation, in 91 pediatric patients with recurrent ependymoma, medulloblastoma and GBM. Outcome
 measures will be 8-month Progression-Free Survival (PFS), and 18-month Overall Survival (OS) and Time
 to Regimen Failure (TTRF), as compared to PFS and OS from historical controls.
Aim 2 will conduct a Phase 2 single-arm trial of 30 children with newly-diagnosed diffuse intrinsic pontine
 glioma (DIPG), to test the hypothesis that front-line indoximod added to standard conformal radiotherapy,
 followed by maintenance chemo-immunotherapy with indoximod + TMZ, will result in improved Overall
 Survival (OS), compared to well-documented historical controls.
Aim 3 will use mechanistic predictions from novel preclinical models to identify innovative, hypothesis-driven
 immune biomarkers, combined with cell-intrinsic genomic and epigenomic features of the patients' original
 tumors, to ask whether these allow prognostic risk stratification of patient outcomes in Aim 1 and Aim 2.
A successful outcome from the proposed clinical trials has the potential to fundamentally change the approach
to treating children with recurrent or refractory brain tumors. It would also have major implications for
incorporating immunologic therapy directly into the standard treatment for children with high-risk brain tumors,
at the time of front-line treatment, when there is the real possibility of long-term cure.

## Key facts

- **NIH application ID:** 10242089
- **Project number:** 5R01CA229646-03
- **Recipient organization:** AUGUSTA UNIVERSITY
- **Principal Investigator:** Theodore S Johnson
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $581,700
- **Award type:** 5
- **Project period:** 2019-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242089

## Citation

> US National Institutes of Health, RePORTER application 10242089, Chemo-radio immunotherapy for pediatric brain tumors (5R01CA229646-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242089. Licensed CC0.

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