Phase 1 study of the angiopoietin 1/2 neutralizing peptibody, trebananib, in acute myeloid leukemia.

7082 Background: Angiopoietins (Ang-1/2), pro-angiogenic factors binding to the Tie2 receptor on endothelial cells, have been implicated in the pathogenesis of acute myeloid leukemia (AML). Trebananib is a first-in-class neutralizing peptibody that potently inhibits Ang-1/2 by sequestering these factors and preventing their interaction with Tie2. Methods: We performed a phase 1b trial evaluating the safety, tolerability, pharmacokinetics (PK) and biologic effects of trebananib in AML patients (pts). Drug was administered at 2 doses (15 and 30 mg/kg) via weekly IV infusion over 1 hour alone (arm A) or in combination with low dose cytarabine (arm B). PK samples were collected at end of infusion (EOI), and 1-3, 4-6, 72, and 168 hrs after EOI on days 1 and 22. Plasma angiogenic factors were assessed by multiplex flow cytometry prior to first dose, on cycle 1 day 29, and at the end of study. Results: Twenty-four pts were enrolled. Median age was 74 years (range 29-84). Sixteen (67%) were male. Six had de novo,...