A participant’s death led to a voluntary pause of a phase I/II dose-escalation trial evaluating MGTA-117 in patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).
The announcement was made by the manufacturer of MGTA-117, Magenta Therapeutics, in a company press release.
The death, which occurred in the participant who most recently received the cohort three dose of 0.08mg/kg, was “deemed to be possibly related to MGTA-117,” according to the company. The participant experienced grade 5 respiratory and cardiac arrest that resulted in death.
“After consultation with the trial’s safety Cohort Review Committee and with the highest regard for patient safety, Magenta has voluntarily paused dosing in the clinical trial and is working to evaluate the totality of available data and determine next steps for the development of MGTA-117,” Magenta Therapeutics officials said in the announcement.
The company announced in late December that it stopped dosing participants at the cohort four dosing level of 0.13 mg/kg and planned to dose additional participants at the cohort three dosing level, as dose-limiting toxicities occurred in two of the three participants that received the cohort four dose. It planned at that time to continue enrollment at the cohort three dose level “in accordance with the clinical trial protocol and following the recommendation of the trial’s safety Cohort Review Committee,” officials said in a news release issued by the company on December 20.
MGTA-117, an anti-CD117 antibody conjugated to an amanitin payload, is designed to deplete CD117-expressing cells in the blood and/or bone marrow before a patient with AML or MDS undergoes hematopoietic stem cell transplantation or receives an ex vivo gene therapy product.
The known information about the death has been reported to the U.S. Food and Drug Administration as a Suspected Unexpected Serious Adverse Reaction, company officials said.
Source: Magenta Therapeutics, December 2022; January 2023