1. A phase 1/2 study of gilteritinib in combination with chemotherapy in newly diagnosed patients with AML in Asia.
- Author
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Sawa M, Miyamoto T, Kim HJ, Hiramatsu Y, Cheong JW, Ikezoe T, Naoe T, Akashi K, Morita S, Kosako M, Ikegaya M, Terada W, Kadokura T, Hill J, Miyawaki S, Gill SC, Heinloth A, and Hasabou N
- Subjects
- Humans, Adult, Middle Aged, Male, Female, Aged, fms-Like Tyrosine Kinase 3 genetics, Asia epidemiology, Maximum Tolerated Dose, Young Adult, Treatment Outcome, Mutation, Remission Induction, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute mortality, Leukemia, Myeloid, Acute diagnosis, Pyrazines administration & dosage, Pyrazines adverse effects, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols adverse effects, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Aniline Compounds administration & dosage, Aniline Compounds adverse effects, Aniline Compounds therapeutic use, Cytarabine administration & dosage
- Abstract
Objective: This interim analysis of a phase 1/2, open-label, single-arm study assessed the safety, efficacy, and pharmacokinetics of gilteritinib plus chemotherapy in adults with newly diagnosed FLT3 mutation-positive acute myeloid leukemia., Methods: In sequential phase 1 and 2 studies, induction and consolidation therapy with gilteritinib 120 mg/day plus chemotherapy (induction: idarubicin/cytarabine once daily; consolidation: cytarabine twice daily) was followed by maintenance gilteritinib 120 mg/day monotherapy. Endpoints included maximum tolerated dose (MTD), recommended expansion dose (RED), and dose-limiting toxicity (phase 1), and complete remission (CR) rate following induction therapy (primary endpoint), overall survival (OS), safety, and pharmacokinetics (phase 2)., Results: In phase 1, MTD was not reached and RED was 120 mg/day. In phase 2, the CR rate was 50.0% after induction (90% confidence interval [CI] 40.4, 59.6); however, the lower confidence limit did not exceed the pre-defined 55% benchmark. Composite CR (CRc) rates were high following induction (86.6%, 95% CI [77.3, 93.1]), consolidation, and maintenance therapy (87.8%, 95% CI [78.7, 94.0], each). The probability of OS was 86.6% at 12 months. No new safety findings were reported., Conclusion: In this interim analysis, gilteritinib 120 mg/day in combination with chemotherapy was well tolerated, with similar CRc rates to previous studies., Competing Interests: Declarations. Conflict of interest: Sawa M reports payment/honoraria from Janssen Pharma and Sanofi. Miyamoto T reports payment/honoraria from Takeda Pharmaceutical Co., Otsuka Pharmaceutical Co., Ltd., MSD Co., Ltd, Astellas Pharmaceutical Co., Ltd., Janssen Co., Ltd., Abbvie Pharmaceutical Co., Ltd., and Kyowa Kirin Pharmaceutical Co. Kim H-J reports consulting fees from Astellas and honoraria from Astellas, and participated in advisory boards for Astellas. Cheong J-W reports payment/honoraria from Astellas, Bristol Myers Squibb, Merck, and GSK, and acted in a leadership/fiduciary role for The Korean Society of Hematology, AML/MDS Working Party, and The Korean Society of Blood and Marrow Transplantation. Naoe T reports payment/honoraria from Bristol Myers Squibb, Pfizer, Nippon Shinyaku, Astellas, Otsuka Pharma, and Japan Tissue Engineering. Akashi K reports grants from Asahi Kasei Pharma, Chugai Pharmaceutical, Kyowa Kirin and Sumitomo Pharma, and payment and/or honoraria from Asahi Kasei Pharma, Astellas, AstraZeneca, Abbvie, Kyowa Kirin, Chugai Pharmaceutical, Bristol Myers Squibb and Janssen Pharmaceuticals. Hill J reports stocks with Ligacept, LLC and is an employee of Astellas Pharma Inc. Kosako M, Ikegaya M, Terada W, Kadokura T, Gill SC, Heinloth A and Hasabou N are employees of Astellas Pharma Inc. Ikezoe T is editor of International Journal of Hematology. Hiramatsu Y, Morita S, and Miyawaki S have no disclosures to report., (© 2024. The Author(s).)
- Published
- 2025
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