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pirtobrutinib + sonrotoclax + obinutuzumab (PSO regimen) is an investigational triple combination therapy being evaluated for the treatment of various B-cell malignancies. The regimen consists of pirtobrutinib, a highly selective, noncovalent (reversible) Bruton tyrosine kinase (BTK) inhibitor; sonrotoclax (also known as sotoclax or BGB-11417), a next-generation BCL-2 inhibitor designed for enhanced potency and selectivity; and obinutuzumab, a glycoengineered type II anti-CD20 monoclonal antibody. By simultaneously inhibiting BTK-mediated B-cell receptor signaling, blocking the anti-apoptotic BCL-2 protein, and targeting CD20-positive B cells for immune-mediated destruction, the PSO regimen aims to overcome resistance mechanisms and achieve deep, durable responses. It is currently under investigation in Phase II clinical trials for patients with histologically transformed diffuse large B-cell lymphoma (DLBCL) and relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
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