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Sonrotoclax + zanubrutinib is an experimental oral combination therapy for B-cell malignancies, particularly chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Sonrotoclax (BGB-11417) is a second-generation BH3-mimetic BCL2 inhibitor with potency >10x that of venetoclax and a short half-life, designed to induce apoptosis in malignant B cells by inhibiting BCL2. Zanubrutinib (BGB-3111) is a next-generation, highly selective Bruton's tyrosine kinase (BTK) inhibitor that blocks B cell receptor (BCR) signaling, suppressing malignant B cell survival and proliferation. The combination has shown potent synergistic activity in recent and ongoing clinical trials, delivering high rates of undetectable minimal residual disease (uMRD) and deep responses with a tolerable safety profile in treatment-naïve CLL patients. No tumor lysis syndrome has been observed with the combination when using a ramp-up protocol, and common side effects include neutropenia, bruising, and mild gastrointestinal events. Phase 3 trials are ongoing to further establish efficacy and safety[1][3][5][7][9].
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