CTIM-05. A PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY HIGH-GRADE GLIOMAS

Rimas Lukas; Surasak Phuphanich; Jeremy Rudnick; Howard Colman; Adam Cohen; Varun Monga; Mohammed Milham; Solmaz Sahebajam; Eugene Kennedy; Christopher Smith; Olivier Rixe

doi:10.1093/neuonc/noab196.197

Back

CTIM-05. A PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY HIGH-GRADE GLIOMAS

Abstract

Open access

Peer reviewed

CTIM-05. A PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY HIGH-GRADE GLIOMAS

Rimas Lukas, Surasak Phuphanich, Jeremy Rudnick, Howard Colman, Adam Cohen, Varun Monga, Mohammed Milham, Solmaz Sahebajam, Eugene Kennedy, Christopher Smith, …

Neuro-oncology (Charlottesville, Va.), Vol.23(Supplement_6), pp.vi50-vi50

11/12/2021

DOI: 10.1093/neuonc/noab196.197

PMCID: PMC8598429

Files and links (1)

url

https://doi.org/10.1093/neuonc/noab196.197View

Published (Version of record) Open Access

Abstract

Abstract BACKGROUND Optimal management of progressive high-grade gliomas (HGG) is not fully defined and outcomes are poor. Indoleamine 2,3-dioxygenase 1 (IDO1) is an enzyme which converts tryptophan to kynurenines, which contribute to the immunosuppresive tumor microenvironment (TME). Targeting the TME by inhibiting IDO1 is a strategy for potential improvement in survival in HGG. METHODS A phase 1/2 trial using the IDO1 inhibitor indoximod was conducted in progressive grade 3 and 4 gliomas. The phase 1 cmponent used a 3 + 3 design escalating indoximod from 600mg po BID to 1200mg po BID in conjunction with temozolomide (150 mg/m2, 5/28 days). The phase 2 component consisted of 3 cohorts: A) indoximod+temozolomide B) indoximod+temozolomide+bevacizumab (patients already on bevacizumab) C) indoximod+temozolomide+stereotactic radiosurgery (SRS). Patients were treated until progression or toxicity. RESULTS 33.3% of patients developed indoximod TEAEs. There were no dose limiting toxicities in the phase 1 component (n=12). 1200 mg BID was established as the phase 2 dose of indoximod. In the phase 2 component (n=148) PFS6 was 74% (A), 93% (B), 70% (C). Median OS was 289 days [10.3 months](A), 159 days [5.7 months](B), 285 days [10.2 months](C). Correlative study results will be available for meeting presentation. CONCLUSIONS The IDO1 inhibitor indoximod proved safe and tolerable in conjunction with temozolomide, bevacizumab, and SRS in patients with progressive HGG. There was a trend toward better survival outcomes when indoximod was combined with temozolomide alone or temozolomide+SRS.

Details

Title: Subtitle: CTIM-05. A PHASE 1/2 STUDY OF THE COMBINATION OF INDOXIMOD AND TEMOZOLOMIDE FOR ADULT PATIENTS WITH TEMOZOLOMIDE-REFRACTORY PRIMARY HIGH-GRADE GLIOMAS
Creators: Rimas Lukas - Northwestern Medicine
Surasak Phuphanich - Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA
Jeremy Rudnick - Cedars-Sinai Medical Center
Howard Colman - University of Utah
Adam Cohen - Inova Health System
Varun Monga - University of Iowa
Mohammed Milham - University of Iowa, Iowa City, IA, USA
Solmaz Sahebajam - Moffitt, Tampa, FL, USA
Eugene Kennedy
Christopher Smith
Olivier Rixe - CHRISTUS St. Vincent Regional Cancer Center
Resource Type: Abstract
Publication Details: Neuro-oncology (Charlottesville, Va.), Vol.23(Supplement_6), pp.vi50-vi50
DOI: 10.1093/neuonc/noab196.197
PMCID: PMC8598429
ISSN: 1522-8517
eISSN: 1523-5866
Language: English
Date published: 11/12/2021
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984363312402771

Metrics

10 Record Views