The U.S. Food and Drug Administration (FDA) has placed clinical holds on several phase I trials of vadastuximab talirine (SGN-CD33A) in patients with acute myeloid leukemia (AML), according to the drug’s manufacturer, Seattle Genetics.
The clinical holds were initiated to assess the risk of hepatotoxicity with vadastuximab talirine (a CD33-directed antibody drug conjugate) following the deaths of four patients who were treated with vadastuximab talirine along with allogeneic hematopoietic cell transplant (AHCT) either prior to or following treatment. All four of these patients had veno-occlusive disease at the time of death; two additional trial participants also had hepatotoxicity.
The drug’s manufacturer reported that the phase I/II trial of single-agent vadastuximab talirine in pre- and post-AHCT patients with AML patients has been placed on full clinical hold, while two other phase I trials have received partial clinical holds, meaning no further enrollment is allowed, but enrolled patients who consent can continue therapy. One of these trials is assessing vadastuximab talirine in combination with hypomethylating agents in older patients with AML; the other is examining vadastuximab talirine in combination with 7+3 chemotherapy in patients with newly diagnosed AML.
Other ongoing trials of vadastuximab talirine (the phase III CASCADE trial in older AML patients and phase I/II trial in myelodysplastic syndrome), are proceeding with enrollment.
Last month, researchers reported data from the phase Ib trial of vadastuximab talirine in combination with 7+3 chemotherapy, finding that the drug was safe in patients with newly diagnosed AML, with patients showing no evidence of increased toxicity or mortality when the drug was added to the standard 7+3 regimen. Seventy-six percent of the 42 patients in this trial also achieved a response, with 60 percent achieving complete remission and 17 percent achieving remission with incomplete blood count recovery.
Source: Seattle Genetics press release, December 27, 2016.