• DOI:10.1093/neuonc/noac139
• Corpus ID: 249233428

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

@article{delaFuente2022OlutasidenibI,
  title={Olutasidenib (FT-2102) in patients with relapsed or refractory IDH1-mutant glioma: A multicenter, open-label, phase Ib/II trial},
  author={Macarena I de la Fuente and Howard Colman and Mark Rosenthal and Brian Andrew Van Tine and Danijela Levacic and Tobias Walbert and Hui Kong Gan and Mar{\'i}a Vieito and Mohammed M Milhem and Kate Lipford and Sanjeev Forsyth and Sylvie Guichard and Yelena Mikhailov and Alexander Sedkov and Julie A. Brevard and Patrick F Kelly and Hesham Mohamed and Varun Monga},
  journal={Neuro-Oncology},
  year={2022},
  volume={25},
  pages={146 - 156}
}

• M. I. de la Fuente, H. Colman, +15 authors V. Monga
• Published 25 May 2022
• Medicine, Biology
• Neuro-Oncology

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.