tuspetinib + venetoclax + azacitidine

**Tuspetinib + venetoclax + azacitidine** is a three-drug combination comprising tuspetinib, a novel oral multi-kinase inhibitor; venetoclax, a BCL-2 inhibitor; and azacitidine, a hypomethylating agent. Tuspetinib targets key prosurvival and oncogenic kinases implicated in acute myeloid leukemia (AML), including SYK, mutant and wild-type FLT3, mutant KIT, RSK2, TAK1–TAB1, and indirectly suppresses expression of MCL1, contributing to direct anti-leukemic effects and synergism with venetoclax. Venetoclax inhibits BCL-2 to drive leukemic cell apoptosis, and azacitidine induces epigenetic modulation and cytotoxicity. The triplet aims to combine broad kinase inhibition, apoptosis induction, and epigenetic therapy for enhanced efficacy in AML, particularly in newly diagnosed patients and in high-risk mutational subtypes. The combination is under investigation, including in the phase 1/2 TUSCANY trial, for its potential to improve remission rates and durable responses in AML, especially for patients ineligible for intensive induction chemotherapy[1][2][3][4][5][6][7].