The first patient enrolled in a Phase 1 clinical trial of XmAb14045 for acute myeloid leukemia (AML) and other CD123-positive hematologic cancers has been dosed, according to an announcement by Xencor.
Contrary to traditional monoclonal antibodies (identical cloned immune cells) that target and bind to a single antigen (foreign substance that triggers immune response), XmAb14045 is a bispecific antibody that targets two distinct antigens, containing a CD123 binding domain and a CD3 binding domain attached to a XmAb Bispecific Fc domain with high stability and long circulating half-life.
The antibody functions by targeting the CD123 molecule expressed at the surface of AML cells and leukemic stem cells, and engages them with the CD3-positive tumor-killing T-cells, which allows a highly potent and targeted elimination of the CD123-positive tumor cells.
CD123 in AML patients is associated with poor prognosis but the experimental drug could change things. Monkey studies have already shown a very effective and potent depletion of CD123-positive cells and few side effects with one intravenous dose.
Xencor’s chief medical officer, Dr. Paul Foster, is optimistic.
“XmAb14045 has shown highly potent killing of tumor cells in preclinical studies and we look forward to studying its safety, tolerability and antitumor activity in clinical trials,” Foster said.
The Phase 1 clinical trial (NCT02730312), which could enroll about 60 adult patients, was designed to determine the safety and tolerability of weekly intravenous administration of XmAb14045 to assess the maximum tolerated dose and best dosing schedule. Eligible patients include those with AML, B-cell acute lymphoblastic leukemia, chronic myeloid leukemia, and other CD123-positive blood cancers.
Worldwide development costs for XmAb14045 are shared by both Xencor and Novartis, with Xencor maintaining U.S. commercial rights and Novartis having commercial rights in the rest of the world.
Currently, Xencor has 10 candidates in clinical development engineered with Xencor’s XmAb technology, including one for B-cell malignancies and one for neuroendocrine tumors, both of which are currently in pre-clinical development. By the end of 2017, Xencor expects to advance some of the candidates into the clinic.