Efficacy and safety of rocbrutinib, a highly selective 4th-generation BTK inhibitor, in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL)

作者：Yuqin Song, Qingqing Cai, Keshu Zhou, Zhengming Jin, Ming Jiang, Xiuhua Sun, Lei Zhang, Haiyan Yang, Lanfang Li, Kaiyang Ding, Junyuan Qi, Min Zhou, Hongmei Jing, Wei Yang, Hui Zhou, Jun Ma, Zhigang Peng, Wei Xu, Yu Li, Yuankai Shi, Guohui Cui, Zheng Wang, Nawei Liu, Yejiang Lou, Yue Shen, Yi Chen, Fenlai Tan, Jun Zhu · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-3896 · 被引用次数：3 · 研究领域：Chronic Lymphocytic Leukemia Research、Protein Degradation and Inhibitors、Ubiquitin and proteasome pathways

Abstract Background Rocbrutinib, a highly selective, 4th-generation Bruton's tyrosine kinase (BTK) inhibitor, uniquely takes advantages of both covalent irreversible inhibition for wide-type BTK and non-covalent binding for C481-mutant variants. Here, we present the safety and efficacy results from the ongoing phase I trial (LP-168-CN101; NCT04993690) of rocbrutinib in Chinese patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Methods Eligible patients aged 18–80 with a confirmed diagnosis of CLL/SLL were treated with rocbrutinib monotherapy until disease progression or intolerable toxicity. Adverse events (AEs) were graded per CTCAE v5.0, and response was evaluated per 2018 iwCLL criteria. Results As of April 15, 2025, 41 (untreated (1L), n=12; relapsed/refractory (R/R) BTKi-naïve, n=17; R/R post-BTKi, n=12) CLL/SLL patients were enrolled and treated with rocbrutinib (100 mg ,n=1; 150 mg, n=28; 200 mg, n=10; 300mg, n=2) once daily. The median age was 60 (range, 35-79) years. Of the patients with evaluable samples, 26.9% (7/26) with del(17p), 42.9% (12/28) with TP53 mutation, 63.0% (17/27) with unmutated IGHV and 44.0% (11/25) with complex karyotype. Of the 29 R/R CLL/SLL patients, the median number of prior therapies was 2 (range, 1-5), including prior covalent BTKis (34.5%), BCL2 inhibitors (BCL-2i, 24.1%), and noncovalent BTKis (6.9%). In R/R post-BTKi CLL/SLL patients, most (91.7%) discontinued prior BTKi due to disease progression; 41.6% had...