Summary
Indoximod was developed to inhibit the IDO (indoleamine 2,3-dioxygenase) enzymatic
pathway, which is important in the natural regulation of immune responses. This potent
immune suppressive mechanism has been implicated in regulating immune responses in
settings as diverse as infection, tissue/organ transplant, autoimmunity, and cancer. By
inhibiting the IDO pathway, we hypothesize that indoximod will improve antitumor immune
responses and thereby slow the growth of tumors.
The central clinical hypothesis for the GCC1949 study is that inhibiting the pivotal IDO
pathway by adding indoximod immunotherapy during chemotherapy and/or radiation is a
potent approach for breaking immune tolerance to pediatric tumors that will improve
outcomes, relative to standard therapy alone.
This is an NCI-funded (R01 CA229646, MPI: Johnson and Munn) open-label phase 2 trial
using indoximod-based combination chemo-radio-immunotherapy for treatment of patients age
3 to 21 years who have progressive brain cancer (glioblastoma, medulloblastoma, or
ependymoma), or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Statistical
analysis will stratify patients based on whether their treatment plan includes up-front
radiation (or proton) therapy in combination with indoximod. Central review of tissue
diagnosis from prior surgery is required, except non-biopsied DIPG. This study will use
the "immune-adapted Response Assessment for Neuro-Oncology" (iRANO) criteria for
measurement of outcomes. Planned enrollment is up to 140 patients.