A Novel Dual Covalent and Non-Covalent Next Generation Inhibitor of Bruton's Tyrosine Kinase LP-168 in Patients with Relapsed/Refractory B Cell Non-Hodgkin Lymphoma: Safety and Efficacy Results from a Phase 1 Study

作者：Yuqin Song, Qingqing Cai, Ming Jiang, Keshu Zhou, Lei Zhang, Xiuhua Sun, Zhengming Jin, Lanfang Li, Hongmei Jing, Zhigang Peng, Haiyan Yang, Junyuan Qi, Hui Zhou, Wei Yang, Min Zhou, Chunyan Ji, Wei Xu, Kaiyang Ding, Yu Li, Zheng Wang, Nawei Liu, Yejiang Lou, Yue Shen, Yi Chen, Fenlai Tan, Jun Zhu · 发表于：Blood · 年份：2023 · DOI：10.1182/blood-2023-180485 · 被引用次数：6 · 研究领域：Chronic Lymphocytic Leukemia Research、Lymphoma Diagnosis and Treatment、CAR-T cell therapy research

Background: Covalent (c) Bruton tyrosine kinase inhibitors (BTKis) have improved clinical outcomes and revolutionized the treatment landscape of several B cell Non-Hodgkin Lymphoma (B-NHL), including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). However, cBTKi intolerance and resistance remain the main causes of treatment failure. LP-168 is a highly selective, next-generation BTKi with high bioavailability and potency. It can act as a cBTKi which irreversibly inhibits wildtype BTK while can overcome the resistance of cBTKi by non-covalent binding and reversible inhibition of C481 mutated BTK. In this abstract are the results from a Phase 1 trial (NCT04993690) that evaluates the safety and efficacy of LP-168 monotherapy in Chinese patients with relapsed/refractory (R/R) B-NHL. Methods: This multicenter Phase 1 study contains a “3+3” dose escalation part (Phase 1a) followed by a dose expansion part (Phase 1b). Subjects with R/R B-NHL are eligible to receive LP-168 once daily treatment until disease progression or unacceptable toxicity. This study was designed to evaluate the safety, tolerability, and pharmacokinetic (PK) profile of LP-168. The efficacy assessment was based on Lugano 2014, 2018 International Workshop on CLL (iwCLL) and the 6 th International Workshop for WM response criteria. Results: Between 10 August 2021 and 31 May 2023, 68 subjects (33 MCL, 14 diffuse large B cell lymphoma [DLBCL], 15 marginal zone lymphoma...