Sponsor Decision

This research study is designed to selectively deplete CD117-positive cells from participants with AML and MDS-EB.

This is a multicenter, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and potential anti-leukemia activity and to establish the minimum safe and biologically-effective dose of a single dose of MGTA-117 in relapsed/refractory (R/R) CD117+ AML participants and participants with MDS-EB. The study consists of escalating single-dose cohorts using a standard 3+3 design.

Inclusion Criteria:

1. Participant must have a World Health Organization (WHO)-defined diagnosis of R/R AML and meet one of the following criteria:

   - The participant has experienced primary AML induction failure or R/R AML

   OR

   - The participant has a WHO-defined diagnosis of MDS-EB and has failed/is refractory to HMA

   OR

   - Presence of MRD in morphologic CR

2. CD117+ based on IHC or flow cytometry

3. Participant must have an identified HSC donor (related donor or unrelated donor), haplo-identical transplant donor, or umbilical blood donor.

4. Participant's Eastern Cooperative Oncology Group (ECOG) performance status must be ≤2.

5. Participant must have adequate baseline hepatic function. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤2 x upper limit of normal (ULN), and serum bilirubin ≤1.5 x ULN.

6. Estimated creatinine clearance ≥60 mL/min

7. Adequate cardiac function as demonstrated by cardiac left ventricular ejection fraction ≥40% or perform New York Heart Association (NYHA) classification I and II

Exclusion Criteria:

1. Acute promyelocytic leukemia (APL).
2. Known active central nervous system (CNS) leukemia or chloroma (granulocyte sarcoma).
3. Received HSCT within 6 months prior to dosing
4. Received chimeric antigen-receptor cell therapies within 6 months prior to dosing
5. Has active graft-versus-host disease (GVHD).
6. Active hepatitis B (Hep-B) or hepatitis C (Hep-C) infection or history of human immunodeficiency virus (HIV).
7. Participant with a QTc value >470 msec
8. Participant has received another investigational drug or device within 14 days or 5 half-lives of dosing, whichever is longer.
9. Participant has any clinically significant medical condition, which in the opinion of the Investigator may place the participant at an unacceptable risk.
10. Active uncontrolled systemic bacterial, fungal, or viral infection
11. Participant has a history of serious allergic reactions, which in the opinion of the Investigator may pose an increased risk of serious infusion reactions.
12. Participant has had any systemic antileukemia treatment within 14 days except hydroxyurea, which is permitted until 24 hours prior to MGTA-117 dosing.
13. Participant has received prior anti-CD117 antibody treatment.
14. Participant has received gemtuzumab ozogamicin (Mylotarg) within the last 3 months prior to dosing.
15. Participant has received recent monoclonal antibody as anti-leukemic therapy within the last 30 days or 5 half-lives, whichever is longer.
16. Participant has received recent vaccination within the last 14 days prior to dosing.
17. Participant has Grade 2 or higher electrolyte abnormality at screening