eligibility_summary
≥18 with CD123+ AML unfit for intensive chemo: ≥75, or 18–74 with ECOG 2–3, cardiac, pulmonary, CrCl 30–<45, or moderate hepatic impairment. ECOG 0–2 if ≥75, 0–3 if 18–74, AST/ALT ≤3×ULN, bilirubin by age/leukemia. Exclusions: uncontrolled illness/infection, active 2nd cancer, HIV on ART/active HBV/HCV, recent autoimmune tx, ≤3‑mo survival, narrow‑TI CYP meds, ≥Gr2 AEs, APL, NYHA≥2, QTcF>470, prior AML tx incl HMA/ven/chemo/experimental, recent CYP3A inducers.
trial_source
clinical_trials.gov from Dec 2, 2025
annotation_status
ai
ai_summary
Phase 1/2 master protocol in CD123+ hematologic malignancies (Substudy 01: newly diagnosed AML unfit for intensive chemo) evaluates SAR443579 + azacitidine + venetoclax. SAR443579: biologic, IV natural killer cell engager (NKCE) that binds CD123 on leukemic cells and co-engages activating receptors on NK cells, inducing NK-mediated cytotoxicity. Azacitidine: hypomethylating agent/DNA methyltransferase inhibitor that causes DNA hypomethylation and cytotoxicity, potentially increasing tumor antigen expression. Venetoclax: small-molecule BCL-2 inhibitor (BH3 mimetic) that restores mitochondrial apoptosis. Targets and pathways: CD123+ AML blasts/leukemic stem cells, NK-cell activation pathways, epigenetic (DNMT) modulation, anti-apoptotic BCL-2 pathway.