Stem-cell transplant biotech Magenta Therapeutics announced this week that it would be pausing the dosing for one of its cohorts in its acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) MGTA-117 trial, due to dose-limiting toxicities reported in two patients.
According to the company, in the group, cohort 4, dose-limiting toxicities (DLT) were observed in the third and fourth participants given the drug. MGTA-117 is an anti-CD117 antibody conjugated to an amanitin payload. CD117, also known as the c-Kit receptor, is highly expressed on hematopoietic stem cells, progenitor cells, and cancer blast cells.
Just a week before the recent announcement of the adverse events, Magenta had shared positive data from the trial at the American Society of Hematology Annual Meeting (ASH), saying then that preliminary clinical results from 15 patients across three dose-escalation cohorts of the ongoing trial showed single-agent activity with no dose-limiting toxicities.
Now, Magenta is saying that it was reported to them on December 13th that the second dose participant experienced a Grade 4 Serious Adverse Event (SAE) (respiratory) considered possibly related to MGTA-117 which was later determined to be a dose-limiting toxicity. The company said that a few days later, on December 15th, it received confirmation of another respiratory SAE, also determined to be a dose-limiting toxicity. Magenta said in its most recent announcement that both patients are improving.
Following the recommendation of the trial’s safety Cohort Review Committee earlier this week, the company will continue enrollment at the Cohort 3 level. The results presented at the ASH conference showed that three out of the four participants in Cohort 3 for whom paired bone marrow samples were collected at baseline and post-dosing showed a depletion of cancer blast cells in both blood and bone marrow.
Magenta has reported the first adverse event to the FDA and has committed to sharing applicable information about the second DLT event soon.