Phase 2 bellwave-003 cohort f: Updated clinical outcomes of nemtabrutinib in participants with relapsed or refractory marginal zone lymphoma

作者：Alessandra Tucci, Yair Herishanu, Juan Dupont, Sarit Assouline, Lori A. Leslie, Thor Høyer, Pier Luigi Zinzani, Yan Xu, Mohammed Z.H. Farooqui, Jing Yang, Muhıt Özcan · 发表于：Blood · 年份：2025 · DOI：10.1182/blood-2025-1801 · 被引用次数：1 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、CAR-T cell therapy research

Abstract Introduction: Covalent Bruton tyrosine kinase inhibitors (BTKis) are approved for use in patients with relapsed or refractory (R/R) marginal zone lymphoma (MZL). However, therapeutic alternatives remain limited for patients who experience disease progression or are unable to tolerate these therapies. Nemtabrutinib, a potent, noncovalent, reversible BTKi taken by mouth (PO) once daily (QD), has shown promising antitumor activity in various B-cell malignancies. Nemtabrutinib has additional activity versus ibrutinib against Src family kinases and kinases related to ERK signaling, which may produce robust responses. Analysis of nemtabrutinib-treated cell lines using next-generation sequencing showed a lack of mutation in BTK and PLCG2 domains, which contrasts with other covalent and noncovalent BTKis such as ibrutinib and pirtobrutinib, respectively. Furthermore, nemtabrutinib has also showed preclinical efficacy in cell lines carrying BTK mutations derived from patients treated with pirtobrutinib. The phase 2 BELLWAVE-003 study (NCT04728893) was designed to evaluate nemtabrutinib in participants with hematologic malignancies. After a median study follow-up of 9.2 months for cohort F of BELLWAVE-003, nemtabrutinib was shown to have antitumor activity and a manageable safety profile at the recommended phase 2 dose (RP2D) of 65 mg QD in participants with MZL that is R/R to ≥2 prior lines of systemic therapies, including covalent BTKis. Outcomes after additional follow-up a...