Pdct-06. Radio-immunotherapy Using the Ido-inhibitor Indoximod in Combination With Re-irradiation for Children With Progressive Brain Tumors in the Phase 1 Setting: an Updated Report of Safety and Tolerability (nct02502708)
Year: 2017
Type: conference-abstract
Abstract: The indoleamine 2,3-dioxygenase (IDO) pathway is a natural immune-checkpoint mechanism often exploited by tumors to escape anti-tumor immunity. Small-molecule IDO pathway inhibitor drugs, such as indoximod, are in multiple trials for adults. Combining indoximod immunotherapy with re-irradiation is a highly innovative approach for treating children with progressive brain cancer. The goal of this first-in-children trial is to assess the feasibility, safety, and preliminary evidence of efficacy of combining indoximod either with temozolomide, or with radiation followed by maintenance therapy with indoximod/temozolomide, for children age 3 to 21 with progressive malignant brain tumors. The study includes two dose-escalation cohorts using a standard 3 + 3 design to determine a recommended phase-2 dose (RP2D) for indoximod in combination with either temozolomide (planned n=12) or radiation (planned n=12). Indoximod dose-levels are 80%, 100%, and 120% of the adult RP2D. We present up-to-date toxicity/side-effect data and follow-up results for all patients treated with indoximod plus radiation. Currently, 26 children have enrolled, and 15 of these have been treated with indoximod plus radiation, including children with ependymoma (n=9), medulloblastoma (n=3), glioblastoma (n=1), bithalamic glioma (n=1), PNET (n=1). Some children received more than one radiation plan over time. All patients were heavily pre-treated, and many patients required target volume and dose adaptation to reduce toxicity risks. Among patients treated to date, median total radiation dose was 30 Gy (range 14-54 Gy), median number of radiation fraction was 20 (range 1-30), and median follow-up duration was 8 months (range 2-15 months). Overall, indoximod combined with re-irradiation has been well tolerated with manageable adverse events. To date, all patients have been able to complete their planned radiation and start maintenance therapy with indoximod/temozolomide without delay. The combination of indoximod and radiation has been well tolerated in this patient population with good overall quality-of-life.
Source: Neuro-Oncology
Authors: Theodore S Johnson, Dolly Aguilera, Ahmad Al-Basheer, Raven M Cooksey, Bree R Eaton, Natia Esiashvili, Selim Firat, John B Fiveash, Nicholas Foreman, Diana Fridlyand, Gregory K Friedman, Cole A Giller, David R Grosshans, Ian M Heger, Michael Kelly, Eugene P Kennedy, Jeffrey Knipstein, Ravindra B Kolhe, Arthur K Liu, William Martin, Waleed F Mourad, Rafal Pacholczyk, Rebecca Parker, Amyn M Rojiani, Ramses F Sadek, Allan Thornton, Nicholas N Vahanian, Tobey MacDonald, David Munn
Institutions: Augusta University, Emory University, Children's Healthcare of Atlanta, Children's Hospital of The King's Daughters, Winship Cancer Institute, Children's Hospital of Wisconsin, Medical College of Wisconsin, University of Alabama at Birmingham, Children's Hospital Colorado, The University of Texas MD Anderson Cancer Center, Akron Children's Hospital, NewLink Genetics (United States), University of Colorado Anschutz, Hampton University
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2767993501