ArticleCancer science2019
Phase I study of tirabrutinib (ONO-4059/GS-4059) in patients with relapsed or refractory B-cell malignancies in Japan.
Article in Cancer science, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Efficacy and safety of tirabrutinib monotherapy in relapsed or refractory B-cell lymphomas/leukemia: a meta-analysis.Frontiers in pharmacology · 2025Pooled it
- A multicenter, open-label, phase II study of tirabrutinib (ONO/GS-4059) in patients with Waldenström's macroglobulinemia.Cancer science · 2020Trial
- Post-marketing surveillance of tirabrutinib for Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma in Japan.Journal of clinical and experimental hematopathology : JCEH · 2026Article
- Administration of tirabrutinib suspension in a patient with primary central nervous system lymphoma: A case report.Oncology letters · 2026Article
- Post-marketing surveillance of tirabrutinib in 189 patients with r/r primary central nervous system lymphoma.Future oncology (London, England) · 2025Observational
- A Comprehensive Review of Small-Molecule Inhibitors Targeting Bruton Tyrosine Kinase: Synthetic Approaches and Clinical Applications.Molecules (Basel, Switzerland) · 2023Review
- Long-term safety profile of tirabrutinib: final results of a Japanese Phase I study in patients with relapsed or refractory B-cell malignancies.International journal of hematology · 2023Article
- CAR T-Cell therapy for the management of mantle cell lymphoma.Molecular cancer · 2023Review
- Bruton tyrosine kinase inhibitors in the management of Waldenström macroglobulinemia.American journal of hematology · 2023Review
- B-cell targeted therapy of pemphigus.The Journal of dermatology · 2023Review
- Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma Associated with Nephrotic Syndrome during Hemodialysis, Treated Successfully with Tirabrutinib.Internal medicine (Tokyo, Japan) · 2022Article
- Evaluation of the potential for pharmacokinetic interaction between tirabrutinib and levonorgestrel/ethinyl estradiol in healthy female volunteers.Clinical and translational science · 2022Article
- Semi-Mechanistic PK/PD Modeling and Simulation of Irreversible BTK Inhibition to Support Dose Selection of Tirabrutinib in Subjects with RA.Clinical pharmacology and therapeutics · 2022Article
- Ibrutinib-Associated Cardiotoxicity: From the Pharmaceutical to the Clinical.Drug design, development and therapy · 2022Review
- Bruton Tyrosine Kinase Inhibitors in B-Cell Malignancies: Their Use and Differential Features.Targeted oncology · 2022Review
- Chimeric antigen receptor (CAR) T-cell treatment for mantle cell lymphoma (MCL).Therapeutic advances in hematology · 2022Review
- Kinase Inhibition in Relapsed/Refractory Leukemia and Lymphoma Settings: Recent Prospects into Clinical Investigations.Pharmaceutics · 2021Review
- BTK Inhibitors in Chronic Lymphocytic Leukemia.Current hematologic malignancy reports · 2021Review
- Non-Covalent BTK Inhibitors-The New BTKids on the Block for B-Cell Malignancies.Journal of personalized medicine · 2021Review
- Biologic therapy in Sjögren's syndrome.Clinical rheumatology · 2021Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 1 country.
Funding
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 showed ≥50% reductions in tumor diameter. In many patients, the tumor size decreased soon after beginning treatment. The maximum serum concentration for tirabrutinib was 611, 1220, 1280 and 886 ng/mL on Day 1 and 484, 971 1940, and 961 ng/mL on Day 28 for Cohorts 1-4, respectively. Tirabrutinib pharmacokinetics were linear, with little accumulation following multiple doses. Tirabrutinib was well tolerated and showed promising efficacy for B-cell NHL/CLL.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.