The US Food and Drug Administration (FDA) has placed a partial clinical hold on biopharmaceutical firm Xencor ’s Phase I trial of XmAb14045.
The move comes after the company submitted the latest safety reports on two patient deaths, which were considered to be possibly associated with the therapeutic molecule.
XmAb14045 is a tumour-targeted, bispecific antibody that comprises CD123 binding domain along with CD3 cytotoxic T-cell binding domain.
The trial is being conducted in patients with relapsed or refractory acute myeloid leukaemia and those suffering from other CD123-expressing hematologic malignancies.
Under the partial clinical hold, patients already receiving treatment in the study may continue, but no new participants can be enrolled until the hold is lifted by the regulatory agency.
Of the two deaths, one was said to be due to cytokine release syndrome (CRS) following first dose of XmAb14045, while the other patient developed acute pulmonary oedema after several doses.
The FDA will have to review additional details about these events, safety and efficacy data across the trial, and amendments to the study protocol and related documents.
Xencor president and CEO Bassil Dahiyat said: “We are working with the investigators and the FDA and will provide an update when more information about resuming enrolment can be shared.
“Our ongoing Phase I studies evaluating our other CD3 bispecific antibodies, XmAb13676 and XmAb18087, are not affected.”
The company commenced XmAb14045 dosing in the Phase I trial in September 2016. The trial aims to determine the safety and tolerability of a weekly intravenous dose of the drug candidate as well as its maximally tolerated dose / dosing schedule.
In December last year, Xencor presented initial results from the trial at the 2018 American Society of Hematology (ASH) Annual Meeting.
Out of the total 66 relapsed / refractory AML patients, 55% experienced cytokine release syndrome (CRS) as the most common toxicity.
Data also showed that 28% of evaluable patients achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) at the two highest initial dose levels.