On December 20, 2022 Magenta Therapeutics (Nasdaq: MGTA) reported that, per the clinical trial protocol for the MGTA-117 Phase 1/2 Dose Escalation Clinical Trial in relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), it has stopped dosing participants at the Cohort 4 dosing level (0.13 mg/kg) and plans to dose additional participants at the Cohort 3 dosing level (0.08 mg/kg) (Press release, Magenta Therapeutics, DEC 20, 2022, View Source [SID1234625445]).
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Three participants have been dosed in Cohort 4, and dose-limiting toxicities (DLTs) were observed in the second and third dosed participants. The first participant completed the 21-day DLT observation period with no DLTs. Subsequent to the Company’s investor presentation on December 13, 2022, it was reported to the Company that the second dosed participant in Cohort 4 experienced a Grade 4 Serious Adverse Event (SAE) (respiratory) considered possibly related to MGTA-117. This SAE was later determined to be a DLT and a Suspected Unexpected Serious Adverse Reaction (SUSAR) due to lung involvement. This participant also experienced Grade 4 aspartate transaminase (AST) and Grade 3 alanine transaminase (ALT) elevations without clinically significant changes in bilirubin, gamma glutamyl transferase or alkaline phosphatase. On December 15, 2022, the Company received a report of a respiratory SAE for the third dosed participant. This SAE was subsequently determined to be the second DLT in Cohort 4, thereby triggering prespecified stopping rules for further dosing in Cohort 4. As of the date of this press release, the clinical trial sites have reported that the first participant with a DLT has demonstrated improved respiratory status and AST/ALT enzyme levels, and the second participant with a DLT had improved respiratory status.
Magenta reported the clinical data and other information applicable to the first observed DLT to the U.S. Food and Drug Administration (FDA) today. Magenta also informed the FDA that the information applicable to the DLT event in the second participant is forthcoming.
In accordance with the clinical trial protocol and following the recommendation of the trial’s safety Cohort Review Committee on December 19, 2022, Magenta plans to continue enrollment at the Cohort 3 dose level. As presented at the 2022 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting on December 12, 2022, no DLTs were observed in the fifteen participants dosed in the first three Cohorts in the clinical trial. Three out of the four participants in Cohort 3 for whom paired bone marrow samples were collected at baseline and post-dosing had depletion of cancer blast cells in both blood and bone marrow. The Company continues to believe that the benefit/risk profile at the Cohort 3 dose level is acceptable to continue enrolling participants in this trial.