The latest patient enrolled in cohort 3 of the phase 1/2 MGTA-117 trial experienced a grade 5 serious adverse event resulting in death. The study has been halted to investigate the safety of the agent.
The ongoing phase 1/2 MGTA-117 trial (NCT05223699) of patients with relapsed/refractory acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) has been voluntarily paused due to the death of a patient, according to Magenta Therapeutics.1
This latest patient was dosed with MGTA-117 at a dose of 0.08 mg/kg and experienced grade 5 serious adverse events (SAEs) of respiratory failure and cardiac arrest, which ultimately resulted in death. With the possible correlation to MGTA-117, the company has reported the known information to the FDA as a suspected unexpected serious adverse reaction.
Previously in December 2022, data from 15 patients who were treated across the first 3 dose cohorts of the trial showed that there were no SAEs observed deemed to be drug related. Further, there were no dose-limiting toxicities seen.2
When the company stepped up to the fourth dose, they quickly ran into problems as grade 3 and 4 SAEs were observed in patients who received the higher dose of 0.13 mg/kg. This led the trial to drop back down to the third dose level.
However, this de-escalation has failed to tame the safety problems as the most recent patient given a dose of 0.08 mg/kg experienced respiratory failure and cardiac arrest, possibly related to MGTA-117, which led to death.
Additionally, the company’s discussion with the trial’s safety cohort review committee has led to the voluntary pause of dosing in the trial. Experts are now working to evaluate data currently available to them and determine next steps for the development of MGTA-117.
MGTA-117 is a novel antibody drug conjugate which targets CD117. The product is currently in development as a single agent for myeloid conditioning prior to hematopoietic stem cell transplantation.
In the multicenter, open-label, dose-escalation study, investigators are evaluating the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and potential anti-leukemia activity of MGTA-117 in patients with AML and MDS. The trial also looks to establish the minimum safe and effective dose of the agent at a single dose for patients with relapsed/refractory CD117-positive AML participants and MDS.3
The trial is utilizing a standard 3+3 design and escalating single-dose cohorts will be evaluated. In the study, MGTA-117 will be administered via intravenous infusion.
Enrollment in the trial is open to patients aged 18 years and older with relapsed or refractory AML who wither has experienced primary AML induction failure or relapsed/refractory AML, or who has a WHO diagnosis of myelodysplasia-excess blasts and has failed or is refractory to HMA, or who has a presence of minimal residual disease in morphologic complete response. Other enrollment requirements include being CD117-positive based, having an identified HSC donor, haplo-identical transplant donor, or umbilical blood dono, an ECOG performance score of 0-2, adequate baseline hepatic function and cardiac function, and an estimated creatinine clearance ≥60 mL/min.
Primary end points of the study include incidence rate of treatment-emergent adverse events (TEAEs) that lead to discontinuation of the study treatment, incidence of TEAEs that are grade 3 and greater, to assess the clinically significant changes from baseline in vital signs, ECGs and laboratory parameters, PK, PD, and to establish a minimum safe and biologically effective dose of MGTA-117.