Phase I study of tirabrutinib (ONO-4059/GS-4059) in patients with relapsed or refractory B-cell malignancies in Japan

Cancer Science
Wataru MunakataKensei Tobinai

Abstract

We evaluated the safety, efficacy, pharmacokinetics, pharmacodynamics and predictive biomarkers of tirabrutinib, a second-generation, enhanced-selectivity Bruton's tyrosine kinase inhibitor in Japanese patients with relapsed/refractory B-cell non-Hodgkin lymphoma (B-cell NHL) and chronic lymphocytic leukemia (CLL). This was an open-label, multicenter, phase I study. Seventeen patients (male N = 8) with a median age of 70 years were enrolled in 4 dose cohorts (160 mg once daily [N = 3], 320 mg once daily [N = 3], 480 mg once daily [N = 4] and 300 mg twice daily [N = 7]); 4 patients had continued tirabrutinib administration as of 4 January 2018. The maximum tolerated dose was not reached. Pneumonitis (N = 1) was the dose-limiting toxicity for 300 mg twice daily. Common adverse events (AEs) were rash (35.3%) and vomiting (29.4%). Eight patients (47.1%) developed grade ≥3 AEs: neutropenia (23.5%), anemia (11.8%) and leukopenia (11.8%) were frequent. The overall response rate (≥PR) was 76.5% (13/17 patients), including 4 DLBCL patients with no CD79A/B or MYD88 mutations, and 1 CLL patient with a TP53 mutation, providing promising data for future developments. Of 16 patients with measurable lesions during the screening period, 12 sho...Continue Reading

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Citations

Jan 31, 2020·Expert Opinion on Emerging Drugs·Stefano MolicaLuciano Levato
Jul 17, 2020·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Deborah M Stephens, John C Byrd
Jul 28, 2020·Expert Opinion on Drug Safety·Shinichi MakitaKensei Tobinai
May 15, 2020·Expert Opinion on Investigational Drugs·Elżbieta Iskierka-Jażdżewska, Tadeusz Robak
May 10, 2020·Drugs·Sohita Dhillon
Sep 15, 2020·Journal of Thrombosis and Haemostasis : JTH·Jennifer SeriesBernard Payrastre
Oct 28, 2020·Clinical Rheumatology·Qin Shao
Jul 22, 2020·Chemical Reviews·Richard A WardPaul D Smith
Apr 4, 2021·Cancers·Philipp von Hundelshausen, Wolfgang Siess
Mar 30, 2021·Frontiers in Cell and Developmental Biology·H Yesid EstupiñánC I Edvard Smith
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Jun 28, 2021·Hematology/oncology Clinics of North America·Masa Lasica, Constantine S Tam
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Oct 3, 2021·Current Hematologic Malignancy Reports·Sameh Gaballa, Javier Pinilla-Ibarz

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Clinical Trials Mentioned

NCT01659255

Software Mentioned

Phoenix WinNonlin
MedDRA

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