Phase 1/2 Trial Pauses Enrollment for Evaluation of MGTA-117 in AML/MDS After Patient Death

Magenta Therapeutics has voluntarily paused enrollment for a phase 1/2 trial (NCT05223699) evaluating the antibody-drug conjugate (ADC) MGTA-117 in patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) following the death of a patient.¹

The patient assigned to an MGTA-117 dose of 0.08 mg/kg experienced a grade 5 serious adverse effect (AE) of respiratory failure and cardiac arrest, which was deemed to be possibly related to MGTA-117. The company said it has reported known information to the FDA as a suspected unexpected serious adverse reaction.

The trial was paused following a consultation with the trial’s safety cohort review committee. Magenta Therapeutics is currently evaluating available data and determining the next steps for the development of MGTA-117.

MGTA-117 is a novel ADC targeting CD117 in development as a single agent for myeloid conditioning prior to hematopoietic stem cell transplantation (HSCT).²

The phase 1/2 trial was enrolling patients with relapsed/refractory AML who experienced primary induction failure or patients with myelodysplasia–excess blasts (MDS-EB) who failed or were refractory to a hypomethylating agent.³ Patients were also required to have CD117-positive disease per immunohistochemistry or flow cytometry; have an identified HSC donor, haplo-identical transplant donor, or umbilical blood donor; have an ECOG performance status of 2 or less; and have adequate hepatic and cardiac function.

Key exclusion criteria included acute promyelocytic leukemia, known active central nervous system leukemia or chloroma, HSCT within 6 months prior to dosing, CAR T-cell therapies within 6 months prior to dosing, or active graft-vs-host disease.

The study used standard 3+3 design to evaluate 5 different doses of MGTA-117 across 5 single-dose cohorts of 0.02 mg/kg, 0.04 mg/kg, 0.08 mg/kg, 0.13 mg/kg, and 0.19 mg/kg. The primary objectives of the trial were to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and potential anti-leukemia activity of MGTA-117, as well as to establish the minimum safe and biologically effective single dose of MGTA-117.

Previously reported findings presented at the 2022 ASH Annual Meeting from the first 15 patients treated during the study showed that MGTA-117 was well tolerated, with no unexpected or serious treatment-related AEs or dose-limiting toxicities.2 Regarding pharmacokinetics, MGTA-117 was found to rapidly clear from the blood, and the ADC was found to bind to CD117-positive cells in the blood of all patients. MGTA-117 was found to deplete target cells in both the blood and bone marrow.

References

1. Magenta Therapeutics voluntarily pauses the MGTA-117 phase 1/2 dose-escalation clinical trial to investigate drug safety. News release. Magenta Therapeutics. January 25, 2023. Accessed January 26, 2023. http://bit.ly/3H7WMoN
2. Westervelt P, Kebriaei P, Juckett M, et al. MGTA-117, an anti-CD117 antibody-drug conjugated with amanitin, in participants with relapsed/refractory adult acute myeloid leukemia (AML) and myelodysplasia with excess blasts (MDS-EB): safety, pharmacokinetics and pharmacodynamics initial findings from a phase 1/2 study. Blood. 2022;140(Suppl 1):2117–2119. doi:10.1182/blood-2022-162406
3. Study of MGTA-117 in patients with adult acute myeloid leukemia (AML) and myelodysplasia-excess blasts (MDS-EB). ClinicalTrials.gov. Updated November 25, 2022. Accessed January 26, 2023. https://clinicaltrials.gov/ct2/show/NCT05223699