The U.S. Food and Drug Administration has placed a partial clinical hold on Xencor’s Phase 1 clinical trial of XmAb14045 for acute myeloid leukemia and other CD123-positive blood cancers because of two patient deaths that appear to be possibly related to the investigational therapy.
A partial clinical hold is a delay or suspension of part of the clinical work requested under the investigational new drug application. In this case, participants currently on the therapy and benefiting from it may continue treatment, but investigators will not enroll new patients until the hold is removed.
The Phase 1 multiple dose trial (NCT02730312) was designed to assess the safety and tolerability of weekly infusions of XmAb14045 across 105 patients with CD123-positive blood cancers who had failed prior therapies and for whom no standard therapies were available. It was also meant to determine the maximum tolerated dose and best dosing schedule. Dosing started more than two years ago.
After the first dose of treatment, one patient developed cytokine release syndrome, a systemic inflammatory response that can be triggered by certain immunotherapies. Researchers were not able to treat the condition, due to the patient’s decision to withdraw care.
The other study participant experienced pulmonary edema after several doses of the investigational therapy.
The hold will be effective until the FDA is done reviewing details regarding these events, safety, and efficacy information across the study, and amendments to the study protocol and related documents.
“Patient safety is Xencor’s highest concern. We are working with the investigators and the FDA and will provide an update when more information about resuming enrollment can be shared. Our ongoing Phase 1 studies evaluating our other CD3 bispecific antibodies, XmAb13676 [NCT02924402] and XmAb18087 [NCT03411915], are not affected,” Bassil Dahiyat, PhD, president and CEO of Xencor, said in a press release.
XmAb14045 is a bispecific antibody, which targets and binds to two distinct molecules, unlike traditional antibodies that target a single protein.
Specifically, XmAb14045 binds the CD123 molecule at the surface of acute myeloid leukemia cells and leukemic stem cells and engages them with the CD3-positive tumor-killing T-cells, allowing the elimination of CD123-positive tumor cells.