FDA lifts partial hold on Xencor leukemia study

The hold had been placed in February following two deaths in the study, including one in a patient who experienced cytokine release syndrome. The company has amended the trial protocol to mandate monitoring and management of CRS.

A hold placed on an early-stage clinical trial for a bispecific antibody in acute myeloid leukemia two months ago has been lifted, the company developing the drug said.

Monrovia, California-based Xencor said Tuesday that the Food and Drug Administration had lifted the partial hold on its Phase I study of XmAb14045, which it had placed two months ago in response to two patient deaths in the trial. The drug is a CD123 x CD3-targeting bispecific antibody being investigated in patients with relapsed or refractory AML. The partial hold allowed patients already enrolled to continue on treatment, but barred new patients from entering into the trial.

Following the news, shares of Xencor were up slightly on the Nasdaq. The news of the hold in February had caused the company’s shares to fall 7 percent.

“We are working with investigational sites to resume enrollment based on the amended protocol, through which we have sought to enhance the safety of patients participating in the study,” Xencor SVP Paul Foster said in a statement.

In a note to clients, BTIG analyst Thomas Shrader wrote that CD123-targeting monoclonal antibodies like XmAb14045 and MacroGenics’ flotetuzumab look approvable to date based on early data presented at the American Society of Hematology’s 2018 annual meeting. According to the data, the antibodies produced complete response rates of 29.4 percent and 28 percent, respectively. Shrader added that the companies’ bispecific approaches were likely to be competitive against CAR-T therapies targeting CD123 and CD33, based on the CAR-Ts’ toxicity.

The trial page on still states the study is active and not recruiting, though it was last updated shortly after the FDA placed the hold in February. Its enrollment target is 105 patients, and it is taking place at six US sites.

Both patient deaths were deemed at least possibly related to the drug, and one of the patients experienced cytokine release syndrome, a toxicity that can occur when large numbers of cancer cells are killed and release proteins into the bloodstream. As part of an agreement with the FDA, the company said it has amended the study protocol, including adding guidance on monitoring and clinical management of CRS.

CRS is known to occur with other therapies for hematological cancers as well. A notable example is the only bispecific antibody that currently has FDA approval, Amgen’s Blincyto (blinatumomab), a CD19-targeting drug for acute lymphoblastic leukemia. The FDA-approved CAR-T therapies, Novartis’ Kymriah (tisagenlecleucel) and Gilead Sciences’ (axicabtagene ciloleucel) and CAR-Ts in clinical development are also associated with CRS.

Stemline Therapeutics’ Elzonris (tagraxofusp) is a CD123-targeting therapy, approved by the FDA for blastic plasmacytoid dendritic cell neoplasm and in several clinical trials for AML.

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