Phase 1 ATRN-119 ATR kinase inhibitor plus decitabine (DNA methyltransferase inhibitor) in TP53 AML/MDS.

This single-center, open-label Phase 1 study at Washington University School of Medicine (St. Louis) evaluates ATRN-119 (Aprea Therapeutics; an oral small-molecule inhibitor of ATR, a key DNA damage–response kinase) in combination with decitabine (a DNA methyltransferase inhibitor hypomethylating agent). The trial uses dose escalation (including patients with untreated or relapsed/refractory AML or higher-risk MDS regardless of TP53 status) followed by a TP53-altered, previously untreated expansion designed to define the recommended Phase 2 dose for the combo. The scientific angle is synthetic-lethality-style stress on DNA repair: TP53-altered myeloid malignancies are genomically unstable, and adding ATR blockade may deepen or prolong hypomethylating-agent responses. Today, many older/unfit newly diagnosed AML and higher-risk MDS patients are treated with hypomethylating agents (decitabine or azacitidine) often combined with venetoclax; TP53-altered disease still has poor durability, so this explores a targeted DNA damage–response add-on to a familiar backbone.