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**ICP-248 + rituximab** is a combination regimen under investigation in clinical trials for mature B-cell malignancies. ICP-248 (Mesutoclax) is a novel, orally bioavailable, highly selective BCL2 inhibitor that restores apoptosis in cancer cells by antagonizing BCL2, a key anti-apoptotic protein commonly overexpressed in B-cell malignancies. Rituximab is a well-established anti-CD20 monoclonal antibody targeting the CD20 antigen expressed on B cells, resulting in B-cell depletion via antibody-dependent cellular cytotoxicity, complement activation, and direct apoptotic signaling. The combination is being tested for synergistic efficacy, deep remission rates, reduction of minimal residual disease, and favorable safety profile in diseases such as chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and other mature B-cell neoplasms[2][3][5].
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