glofitamab + poseltinib + lenalidomide

Glofitamab + poseltinib + lenalidomide is a combination therapy currently in Phase II clinical trials for relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL). The combination leverages the distinct mechanisms of action of its three components to achieve synergistic anti-tumor effects. Glofitamab is a bispecific T-cell engager (BiTE) that redirects T cells to eliminate cancerous B cells by simultaneously binding to CD20 on B cells and CD3 on T cells. Poseltinib is an orally active, irreversible small molecule inhibitor of Bruton's tyrosine kinase (BTK), which plays a critical role in B-cell proliferation and survival. Lenalidomide is an immunomodulatory imide drug (IMiD) that modulates the substrate specificity of the Cereblon E3 ubiquitin ligase, leading to the proteasomal degradation of key proteins involved in cancer cell survival and also enhancing immune cell function. The rationale for this combination stems from in vitro evidence suggesting synergism between BTK inhibitors and T-cell engagers, and the known synthetic lethality of lenalidomode plus BTK inhibitors against DLBCL. This regimen aims to provide a non-cytotoxic treatment option for patients with R/R DLBCL.

Other names

GPL regimen