ICP-248 + orelabrutinib + rituximab

ICP-248 + orelabrutinib + rituximab is an investigational combination regimen under clinical evaluation for the treatment of hematological malignancies, specifically relapsed or refractory B cell lymphomas. The combination consists of ICP-248 (a small molecule agent, though specific target/mechanism and developer is not established in public sources as of September 2025), orelabrutinib (a selective, covalent Bruton’s tyrosine kinase [BTK] inhibitor enhancing B-cell apoptosis and suppressing BCR signaling), and rituximab (a chimeric monoclonal antibody targeting CD20, resulting in B-cell depletion via cytotoxic and immune-mediated mechanisms). The regimen is under investigation with preliminary data focusing primarily on the efficacy and safety of orelabrutinib combined with rituximab, suggesting advantages in managing relapsed or refractory marginal zone lymphoma (MZL) and other B-cell lymphomas[1][2][3].