ARMY: First-in-human study of the humanized, defucosylated monoclonal antibody (mAb) MEN1112/OBT357 targeting CD157 antigen, in relapsed or refractory (R/R) acute myeloid leukemia (AML).

TPS3100 Background: Defucosylated mAbs enhance antibody dependent cell-mediated cytotoxicity (ADCC) through an improved affinity for Fc receptors. MEN1112/OBT357 is a humanized, defucosylated mAb targeting Bst1/CD157, a GPI-anchored transmembrane protein highly expressed on blasts of AML patients either at primary diagnosis or relapse. Preclinical findings show that MEN1112/OBT357 has the potential to exert powerful ADCC against AML (Aud et al ASH 2014; Venditti et al ASH 2014). Methods: Multi-center, non-randomized, 3+3 dose escalation/expansion cohort trial of MEN1112/OBT357 intended to recruit approximately 50 adult patients (pts) with R/R AML. Refractory pts must have failed ≥ 1 cycle of cytotoxic chemotherapy or hypomethylating agents. A baseline WBC count ≤ 10 x 109/L is required (pre-treatment with hydroxyurea is permitted). Main exclusion criteria are acute promyelocytic leukemia, hematopoietic stem cell transplant within 3 months prior to screening and active central nervous system involvement. M...