Sistema de Salut de Catalunya
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
2023-02-14T13:32:23Z
2023-02-14T13:32:23Z
2023-01
Brain penetration; Mutant; Olutasidenib
Penetració cerebral; Mutant; Olutasidenib
Penetración cerebral; Mutante; Olutasidenib
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.
This study was funded by Forma Therapeutics, Inc., Watertown, MA, USA.
Artículo
Versión publicada
Inglés
Gliomes - Tractament; Medicaments antineoplàstics - Ús terapèutic; DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neoplasms, Neuroepithelial::Glioma; Other subheadings::Other subheadings::Other subheadings::/drug therapy; CHEMICALS AND DRUGS::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents; Other subheadings::Other subheadings::/therapeutic use; ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::neoplasias neuroepiteliales::glioma; Otros calificadores::Otros calificadores::Otros calificadores::/farmacoterapia; COMPUESTOS QUÍMICOS Y DROGAS::acciones y usos químicos::acciones farmacológicas::usos terapéuticos::antineoplásicos; Otros calificadores::Otros calificadores::/uso terapéutico
Oxford University Press
Neuro-Oncology;25(1)
https://doi.org/10.1093/neuonc/noac139
Attribution-NonCommercial 4.0 International
http://creativecommons.org/licenses/by-nc/4.0/
