Phase 1/2 asciminib STAMP BCR-ABL1 inhibitor with FLAG-Ida + venetoclax BCL-2 inhibitor

MD Anderson is running this Phase 1b/2 study to define safety (Phase 1b) and estimate efficacy (Phase 2) of adding asciminib (Novartis; a STAMP inhibitor that targets the ABL myristoyl pocket on BCR-ABL1) to intensive FLAG-Ida chemotherapy (fludarabine + cytarabine + idarubicin + G-CSF) plus venetoclax (AbbVie/Genentech; BCL-2 inhibitor) in advanced-phase CML (myeloid or lymphoid blast phase) and Philadelphia chromosome–positive AML. The trial is open-label with combination therapy, with an additional arm that adds blinatumomab (Amgen; CD19×CD3 bispecific T-cell engager) for CD19-positive disease contexts. The scientific angle is “stacking” deep cytoreduction (FLAG-Ida), apoptosis priming (venetoclax), and potent on-target BCR-ABL1 suppression (asciminib), with optional immune redirection (blinatumomab) to improve remission depth ahead of allogeneic transplant. Today’s care for advanced-phase CML/Ph+ AML typically relies on a potent ABL TKI (often ponatinib when feasible) plus AML-like induction or ALL-like therapy by lineage, then transplant when a remission is achieved; outcomes remain poor, so regimen optimization is clinically and commercially meaningful.