ACTR-53. INTERIM ANALYSIS OF PHASE 1B/2 COMBINATION STUDY OF THE IDO PATHWAY INHIBITOR INDOXIMOD WITH TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY MALIGNANT BRAIN TUMORS

Abstract

BACKGROUND: Indoleamine 2, 3-dioxygenase (IDO) is a key immune-modulatory enzyme within the IDO Pathway that inhibits CD8+ T cells and enhances the suppressor activity of Tregs. IDO is expressed in a large proportion of solid tumors including 50 to 90% of glioblastoma (GBM). IDO high expression is correlated with poor prognosis in GBM. IDO pathway inhibitors such as indoximod can improve anti-tumor T cell response slowing the tumor growth in vivo. We have demonstrated a synergistic effect of indoximod when combined with temozolomide (TMZ) and radiation in a syngeneic orthotopic brain tumor model. The purpose of this phase 1b/2 study is to determine the safety and preliminary efficacy of indoximod in combination with TMZ in recurrent refractory malignant brain tumors.METHODS: After progression on TMZ, patients are eligible for enrollment in this study of indoximod (1200 mg twice daily orally) combined with a standard fixed dose of TMZ (150mg/m2 x 5 days). In the phase 2 expansion, patients are enrolled into 3 cohorts: 2a: indoximod with TMZ (for patients refractory to TMZ), 2b: indoximod with TMZ and bevacizumab (for patients who have progressed on bevacizumab), 2c: indoximod with TMZ in conjunction with stereotactic radiosurgery in select patients. Indoximod is administered for all 28 days of each treatment cycle.