A Study to Investigate Zanubrutinib in Chinese Participants With B-cell Lymphoma

Summary

This phase I clinical study was to investigate the safety, tolerability, and pharmacokinetics/pharmacodynamics of Bruton tyrosine kinase (BTK) inhibitor zanubrutinib (BGB-3111) in Chinese participants with B-cell lymphoma by conducting in two stages, the first stage being the safety assessment of dose and the second stage being the dose expansion. Part I: Safety evaluation - according to the results of preclinical toxicological trials and the results of the phase I clinical study conducted in Australia and New Zealand, two regimens of zanubrutinib 320 milligrams (mg) daily (160 mg twice daily \[BID\]), administered in the morning and at night, or 320 mg once daily \[QD\]) and "3+3" design was adopted for the assessment. The recommended dose and method of administration of the phase II clinical study was determined according to the Part I results. Part II: Dose expansion - this stage was to further evaluate the preliminary anti-tumor effects of zanubrutinib in Chinese participants with follicular lymphoma (FL) or marginal zone lymphoma (MZL), approximately 20 participants with relapsed or refractory FL or MZL were to be enrolled. The recommended Phase 2 dose (RP2D) was used in Part II.

Timeline

Start

2016-07-05

Primary completion

2020-08-26

Completion

2020-08-26

Publications

• Background Jun Zhu, BS, Jianyong Li, MD, Jianfeng Zhou, Yuqin Song, MD, Junyuan Qi, Wei Xu, Dengju Li, MD, Mingyuan Sun, Ling Xue, PhD, Liudi Yang, Yinwei Zhang, Lai Wang, PhD, Jane Huang, MD, Shibao Feng, PhD, Lugui Qiu, MD. BGB-3111, a Highly Specific BTK Inhibitor, Is Well Tolerated and Highly Active in Chinese Patients with Relapsed/Refractory B-Cell Malignancies: Initial Report of a Phase 1 Trial in China. Blood. 2017; 130(1): 5347. https://doi.org/10.1182/blood.V130.Suppl_1.5347.5347
• Moslehi JJ, Furman RR, Tam CS, Salem JE, Flowers CR, Cohen A, Zhang M, Zhang J, Chen L, Ma H, Brown JR. Cardiovascular events reported in patients with B-cell malignancies treated with zanubrutinib. Blood Adv. 2024 May 28;8(10):2478-2490. doi: 10.1182/bloodadvances.2023011641.
• Xu W, Yang S, Tam CS, Seymour JF, Zhou K, Opat S, Qiu L, Sun M, Wang T, Trotman J, Pan L, Gao S, Zhou J, Zhou D, Zhu J, Song Y, Hu J, Feng R, Huang H, Su D, Shi M, Li J. Zanubrutinib Monotherapy for Naive and Relapsed/Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: A Pooled Analysis of Three Studies. Adv Ther. 2022 Sep;39(9):4250-4265. doi: 10.1007/s12325-022-02238-7. Epub 2022 Jul 28.
• Song Y, Sun M, Qi J, Xu W, Zhou J, Li D, Li J, Qiu L, Du C, Guo H, Huang J, Tang Z, Ou Y, Wu B, Yu Y, Zhu J. A two-part, single-arm, multicentre, phase I study of zanubrutinib, a selective Bruton tyrosine kinase inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. Br J Haematol. 2022 Jul;198(1):62-72. doi: 10.1111/bjh.18162. Epub 2022 Apr 5.

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Indications