Sonrotoclax (BGB-11417) monotherapy in patients with Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL) previously treated with a bruton tyrosine kinase (BTK) inhibitor: Early results from A phase 1/2 study

作者：Michael Wang, Yuqin Song, Olivier Hermine, Yue-Rong Shuang, Wojciech Jurczak, João Samuel de Holanda Farias, Carolina Mahuad, Muhıt Özcan, Ron D. Jachimowicz, Tianlei Chen, Elena P. Ivanova, Xiaotong Li, Gabriel Man, Priscille Bourquelot, Remus Vezan, Toby A. Eyre · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-663 · 被引用次数：6 · 研究领域：Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、Chronic Lymphocytic Leukemia Research

Abstract Introduction: MCL is a rare, incurable subtype of B-cell non-Hodgkin lymphoma characterized by a continuous pattern of relapse after initial therapy. While BTK inhibitors are standard of care treatments for R/R MCL and are effective in first line, the population of patients with BTK inhibitor resistance is growing and optimal treatment regimens for patients with disease progression after BTK inhibitors who are ineligible for chimeric antigen receptor-T cell therapy are unknown. Sonrotoclax (BGB-11417), a next-generation B-cell lymphoma 2 (BCL2) inhibitor, is a more selective and pharmacologically potent inhibitor of BCL2 than venetoclax, with a shorter half-life and no drug accumulation. Here, initial phase 1/2 safety and efficacy data are presented for patients with R/R MCL with previous BTK inhibitor exposure and treated with sonrotoclax monotherapy. Methods: BGB-11417-201 (NCT05471843) is an ongoing multicenter, open-label, dose-escalation/expansion study. Eligible adult patients have histologically confirmed MCL per WHO 2016 classification and measurable disease. Patients must have received prior anti-CD20–based therapy and ≥1 BTK inhibitor. In the part 1 dose-escalation and safety expansion, sonrotoclax was orally administered once daily with ramp-up to the target doses of 160 mg and 320 mg. The part 2 efficacy expansion used sonrotoclax at the recommended phase 2 dose (RP2D) and implemented a simplified ramp-up schedule. The primary endpoints were dose-limiting...