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Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial

Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial

Authors :
Macarena I de la Fuente
Howard Colman
Mark Rosenthal
Brian A Van Tine
Danijela Levacic
Tobias Walbert
Hui K Gan
Maria Vieito
Mohammed M Milhem
Kathryn Lipford
Sanjeev Forsyth
Sylvie M Guichard
Yelena Mikhailov
Alexander Sedkov
Julie Brevard
Patrick F Kelly
Hesham Mohamed
Varun Monga
Institut Català de la Salut
[de la Fuente MI] Sylvester Comprehensive Cancer Center and Department of Neurology, University of Miami, Miami, Florida, USA. [Colman H] Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. [Rosenthal M] Peter MacCallum Cancer Centre Melbourne, Victoria, Australia. [Van Tine BA] Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA. [Levacic D] Baylor and Scott White Vasicek Cancer Center, Baylor University Temple, Temple, Texas, USA. [Walbert T] Henry Ford Cancer Institute, Henry Ford Health System and Wayne State University, Detroit, Michigan, USA. [Vieito M] Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain
Vall d'Hebron Barcelona Hospital Campus
Source :
Scientia
Publication Year :
2022
Publisher :
Oxford University Press (OUP), 2022.

Abstract

Background Olutasidenib (FT-2102) is a highly potent, orally bioavailable, brain-penetrant and selective inhibitor of mutant isocitrate dehydrogenase 1 (IDH1). The aim of the study was to determine the safety and clinical activity of olutasidenib in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation. Methods This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (≥18 years) had histologically confirmed IDH1R132X-mutated glioma that relapsed or progressed on or following standard therapy and had measurable disease. Patients received olutasidenib, 150 mg orally twice daily (BID) in continuous 28-day cycles. The primary endpoints were dose-limiting toxicities (DLTs) (cycle 1) and safety in phase I and objective response rate using the Modified Response Assessment in Neuro-Oncology criteria in phase II. Results Twenty-six patients were enrolled and followed for a median 15.1 months (7.3‒19.4). No DLTs were observed in the single-agent glioma cohort and the pharmacokinetic relationship supported olutasidenib 150 mg BID as the recommended phase II dose. In the response-evaluable population, disease control rate (objective response plus stable disease) was 48%. Two (8%) patients demonstrated a best response of partial response and eight (32%) had stable disease for at least 4 months. Grade 3‒4 adverse events (≥10%) included alanine aminotransferase increased and aspartate aminotransferase increased (three [12%], each). Conclusions Olutasidenib 150 mg BID was well tolerated in patients with relapsed/refractory gliomas harboring an IDH1R132X mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.

Details

ISSN :
15235866 and 15228517
Volume :
25
Database :
OpenAIRE
Journal :
Neuro-Oncology
Accession number :
edsair.doi.dedup.....29b253bb132081b03fc3679216acf7f5
Full Text :
https://doi.org/10.1093/neuonc/noac139