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.