Primary analysis of a multicenter, open-label, phase 2 study of sonrotoclax (BGB-11417) monotherapy in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL)

作者：Shuhua Yi, Keshu Zhou, Ning Liu, Wei Sang, Rui Huang, Yi Wang, Chenghui Zhang, Fudao Wu, Ying Li, Mei Sun, Jian‐Qing Mi, Kaiyang Ding, Sujun Gao, Qiaohua Zhang, Haiying Hua, Xiaoxia Chu, Jian Cheng, Aikebaier Abudureyimu, Lanyun Zhou, C. W. Chow, T Y Chen, Zhiyu Liang, Remus Vezan, Lugui Qiu · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-5666 · 被引用次数：1 · 研究领域：Chronic Lymphocytic Leukemia Research、HER2/EGFR in Cancer Research、Calcium signaling and nucleotide metabolism

Abstract Introduction: B-cell lymphoma 2 (BCL2) inhibition is an established treatment strategy in CLL/SLL with the potential to induce deep responses. CLL/SLL treatment guidance in China is similar to that in Western countries; however, novel treatments have limited availability in China. Sonrotoclax (BGB-11417), a next-generation BCL2 inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. In a phase 1 study (NCT04883957), sonrotoclax monotherapy was well tolerated and induced deep responses in Chinese patients (pts) with R/R CLL/SLL, with a 72.4% overall response rate (ORR) and a 41.4% best undetectable measurable residual disease (10−4 sensitivity; uMRD4) rate in blood. Presented here are primary efficacy and safety data for BGB-11417-202 (NCT05479994), an open-label, phase 2 study of sonrotoclax in Chinese pts with R/R CLL/SLL. Methods: Eligible pts had Bruton tyrosine kinase (BTK) inhibitor + chemoimmunotherapy (CIT) intolerance/failure (CIT not mandatory if pts ineligible for CIT) and no prior BCL2 inhibitor. Pts received sonrotoclax 320 mg once daily, with ramp-up to the target dose, until progressive disease (PD) or unacceptable toxicity. The primary endpoint was independent review committee (IRC)–assessed ORR per iwCLL 2018 guidelines (CLL) or 2014 Lugano criteria (SLL). Secondary endpoints included IRC- and investigator (INV)–assessed duration of response (DOR), progression-fr...