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CTIM-32. FIRST-IN-CHILDREN PHASE 1 TRIAL OF INDOXIMOD-BASED CHEMO-IMMUNOTHERAPY FOR PATIENTS WITH PEDIATRIC BRAIN TUMORS: ANALYSIS OF SAFETY, TOLERABILITY, AND 5-YEAR OUTCOME

Authors :
Theodore Johnson
Rafal Pacholczyk
Dolly Aguilera
Ahmad Al-Basheer
Manish Bajaj
Pratiti Bandopadhayay
Zuzana Berrong
Eric Bouffet
Robert Castellino
Kathleen Dorris
Bree Eaton
Natia Esiashvili
Nicholas Foreman
Diana Fridlyand
Cole Giller
Ian Heger
Nadja Kadom
Eugene Kennedy
Neevika Manoharan
William Martin
Colleen McDonough
Rebecca Parker
Vijay Ramaswamy
Eric Ring
Amyn Rojiani
Ramses Sadek
Amy Smith
Chris Smith
Rachel Vaizer
Kee Kiat Yeo
Tobey MacDonald
David Munn
Source :
Neuro-Oncology. 24:vii68-vii68
Publication Year :
2022
Publisher :
Oxford University Press (OUP), 2022.

Abstract

BACKGROUND Recurrent brain tumors are the leading cause of cancer death in children. We conducted a first-in-children, two-institution, Phase 1 open-label dose-confirmation study using a 3 + 3 design, with expansion cohorts, to determine the recommended pediatric dose of the IDO pathway-inhibitor indoximod (NCT02502708). DESIGN/ METHODS Eligible patients were 3-22 years old with either recurrent malignant brain tumor or newly-diagnosed diffuse intrinsic pontine glioma (DIPG). Palliative radiation, surgery or dexamethasone were allowed as needed for patient management. Separate dose-finding arms were performed for indoximod plus temozolomide (200 mg/m2/day orally for 5 days of each 28-day cycle) and for indoximod plus conformal radiation (in patients for whom re-irradiation was planned as standard-of-care). At progression, patients who were otherwise clinically stable were offered crossover to indoximod plus a second-line chemotherapy regimen (cyclophosphamide 2.5 mg/kg/day orally and etoposide 50 mg/m2/day orally for 21 days of each 28-day cycle). RESULTS Between December 2015 and January 2019, the study enrolled 81 brain tumor patients, including newly-diagnosed DIPG (n = 13) or recurrent ependymoma (n = 27), glioblastoma/high-grade glioma (n = 19), medulloblastoma (n = 13), or other CNS tumors ( n= 9). Median follow-up was 52 months (range 39-77 months). No dose-limiting toxicities were observed, and the pediatric indoximod dose was determined (19.2 mg/kg/dose, given twice daily). Indoximod was well tolerated and did not affect the ability to deliver chemotherapy or radiation as planned. Median overall survival was 13.6 months (n = 81). Median overall survival was 34.7 months for the subset of patients who continued indoximod with second-line chemotherapy after progression on indoximod plus temozolomide (n = 18). CONCLUSIONS Indoximod was well tolerated and could be combined with a variety of standard treatments for pediatric brain tumors. Preliminary anti-tumor activity and overall survival suggest that indoximod with standard therapy should be further evaluated in pediatric brain tumors, and potentially other pediatric solid tumors.

Details

ISSN :
15235866 and 15228517
Volume :
24
Database :
OpenAIRE
Journal :
Neuro-Oncology
Accession number :
edsair.doi...........ab01c9865aca474900034e328e975d64