CC-292 + CC-223 + rituximab

This is an investigational **triple combination regimen** comprising CC-292 (a covalent Bruton tyrosine kinase inhibitor), CC-223 (an ATP-competitive mammalian target of rapamycin inhibitor), and rituximab (a monoclonal anti-CD20 antibody), studied for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). The combination leverages diverse mechanisms targeting B-cell receptor signaling (BTK inhibition), PI3K/mTOR signaling, and direct depletion of CD20+ B-cells. CC-292 and CC-223 are small-molecule investigational agents; rituximab is an approved monoclonal antibody. The combination was evaluated in a multi-arm phase Ib clinical trial in heavily pretreated DLBCL patients. However, the CC-292 + CC-223 + rituximab regimen was associated with **enhanced toxicity and/or insufficient improvement in responses** compared to other combinations and was not selected for expansion[1][3][5].