TP-0903 + ibrutinib

**TP-0903 + ibrutinib** is a combination therapy under investigation for the treatment of chronic lymphocytic leukemia (CLL). TP-0903 (also referred to by its generic name dubermatinib) is a novel oral small molecule inhibitor that primarily targets AXL kinase, a member of the TAM (TYRO3, AXL, MER) family of receptor tyrosine kinases, implicated in cancer cell survival, proliferation, and mesenchymal transformation. TP-0903 also shows inhibitory activity against other TAM kinases. It induces apoptosis in CLL B-cells even from patients who have progressed on or are being treated with ibrutinib. Ibrutinib (brand name Imbruvica) is a small molecule inhibitor of Bruton's tyrosine kinase (BTK), a central player in B-cell receptor (BCR) signaling and survival. The combination is being studied due to the upregulation of anti-apoptotic proteins and persistent lymphocytosis seen in CLL after ibrutinib monotherapy. Preclinical and early clinical data suggest TP-0903 can synergistically enhance apoptosis in CLL cells exposed to ibrutinib, providing a rationale for combination use in relapsed/refractory or difficult-to-treat CLL patients[1][2][4][5].

Other names

dubermatinib + ibrutinib