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

de la Fuente, MI; Colman, H; Rosenthal, M; Van Tine, BA; Levacic, D; Walbert, T; Gan, HK; Vieito, M; Milhem, MM; Lipford, K; Forsyth, S; Guichard, SM; Mikhailov, Y; Sedkov, A; Brevard, J; Kelly, PF; Mohamed, H; Monga, V

Author(s): de la Fuente, MI; Colman, H; Rosenthal, M; Van Tine, BA; Levacic, D; Walbert, T; Gan, HK; Vieito, M; Milhem, MM; Lipford, K; Forsyth, S; Guichard, SM; Mikhailov, Y; Sedkov, A; Brevard, J; Kelly, PF; Mohamed, H; Monga, V;
Details: Publication Year 2023,Volume 25,Issue #1,Page 146-156
Journal Title: Neuro-Oncology
Publication Type: Research article
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.
Publisher: Oxford University Press
Keywords: Humans; Pyridines; *Quinolines; *Glioma/drug therapy/genetics; Isocitrate Dehydrogenase/genetics
Department(s): Medical Oncology
PubMed ID: 35639513
Publisher's Version: https://doi.org/10.1093/neuonc/noac139
Open Access at Publisher's Site: https://doi.org/10.1093/neuonc/noac139
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-04-06 06:53:43

Last Modified: 2023-04-17 11:52:08