Journal article
Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial
Neuro-oncology (Charlottesville, Va.), Vol.25(1), pp.146-156
05/25/2022
DOI: 10.1093/neuonc/noac139
PMCID: PMC9825299
PMID: 35639513
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 IDH1(R132X) mutation. Methods This was an open-label, multicenter, nonrandomized, phase Ib/II clinical trial. Eligible patients (>= 18 years) had histologically confirmed IDH1(R132X)-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 IDH1(R132X) mutation and demonstrated preliminary evidence of clinical activity in this heavily pretreated population.
Details
- Title: Subtitle
- Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial
- Creators
- Macarena de la Fuente - Sylvester Comprehensive Cancer CenterHoward Colman - Huntsman Cancer InstituteMark Rosenthal - Peter MacCallum Cancer CentreBrian A. Van Tine - Washington University in St. LouisDanijela Levacic - Baylor UniversityTobias Walbert - Henry Ford Health SystemHui K. Gan - Olivia Newton-John Cancer Wellness & Research CentreMaria Vieito - Vall d'Hebron Institute of Oncology, Barcelona, Spain.Mohammed M. Milhem - University of IowaKathryn Lipford - Forma Therapeutics (United States)Sanjeev Forsyth - Forma Therapeutics (United States)Sylvie M. Guichard - Forma Therapeutics (United States)Yelena Mikhailov - Forma Therapeutics (United States)Alexander Sedkov - Forma Therapeutics (United States)Julie Brevard - Forma Therapeutics (United States)Patrick F. Kelly - Forma Therapeutics (United States)Hesham Mohamed - Forma Therapeutics (United States)Varun Monga - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Neuro-oncology (Charlottesville, Va.), Vol.25(1), pp.146-156
- DOI
- 10.1093/neuonc/noac139
- PMID
- 35639513
- PMCID
- PMC9825299
- NLM abbreviation
- Neuro Oncol
- ISSN
- 1522-8517
- eISSN
- 1523-5866
- Publisher
- Oxford Univ Press
- Number of pages
- 11
- Grant note
- Forma Therapeutics, Inc., Watertown, MA, USA
- Language
- English
- Date published
- 05/25/2022
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984359814702771
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