The US Food and Drug Administration (FDA) has lifted the partial clinical hold placed on Xencor’s Phase I leukaemia study of XmAb14045.
XmAb14045 is a CD123 x CD3 bispecific antibody molecule being evaluated to treat patients with relapsed or refractory acute myeloid leukaemia (AML) and other CD123-expressing hematologic malignancies.
In February this year, the FDA placed a partial clinical hold on Xencor’s Phase I trial of XmAb14045 after the company submitted the latest safety reports on two patient deaths considered to be possibly associated with the therapeutic molecule.
Under the partial hold, patients already receiving treatment in the study continued and no new participants were enrolled until the hold was lifted.
The latest decision comes after Xencor discussed and agreed with the FDA on amendments to the study protocol, including guidance on the monitoring and clinical management of cytokine release syndrome.
Xencor senior vice-president and chief medical officer Paul Foster said: “We are working with investigational sites to resume enrolment based on the amended protocol, through which we have sought to enhance the safety of patients participating in the study.”
The tumour-targeted antibody XmAb14045 contains a CD123 binding domain, as well as a cytotoxic T-cell binding domain (CD3) in the Phase I trial to treat AML and other CD123-expressing hematologic malignancies.
Highly expressed on AML cells and leukemic stem cells, CD123 is associated with poorer prognosis in AML patients.
Engagement of CD3 by XmAb14045 will activate T cells for the highly potent and targeted killing of CD123-expressing tumour cells.