A Study of CTX-712 in Relapsed/Refractory Acute Myeloid Leukemia and Higher Risk Myelodysplastic Syndromes

Inclusion criteria:

1. Age ≥18 years.

2. Diagnosis of AML, HR-MDS, or high marrow blast MDS/MPN (including CMML).

3. Prior treatment history must include 1-4 prior lines of therapy.

4. Adequate organ function evidenced by the following laboratory values: Creatinine clearance (CL) ≥60 mL/min Total serum bilirubin < 1.5 × upper limit ofnormal (ULN) Alanine aminotransferase (ALT) Aspartate aminotransferase(AST) < 2.5 ×ULN White blood cell count at the time of the first dose <10 k/μL

5. Eastern Cooperative Oncology Group performance status ≤2.

6. Female patients of childbearing potential must have a negative pregnancy test within 7 days before study treatment initiation and if sexually active, agree to use ahighly effective form of contraception throughout their participation during studytreatment and up to 4 months after the last dose of study drug

7. Male patients with female partners of childbearing potential must, even ifsurgically sterilized, agree to practice effective barrier contraception during theentire study treatment period and through four months after the last dose of studydrug, or practice true abstinence, when this is in line with the preferred and usuallifestyle of the participant.

Exclusion criteria:

1. Diagnosis of acute promyelocytic leukemia.

2. Isolated extramedullary relapse (phase 2 only).

3. Active central nervous system (CNS) leukemia.

4. History of other malignancy.

5. Any of the following cardiopulmonary abnormalities:

6. Myocardial infarction within six months prior to registration.

7. New York Heart Association Class III or IV heart failure or known leftventricular ejection fraction < 50%.

8. A history of familial long QT syndrome.

9. Symptomatic atrial or ventricular arrhythmias not controlled by medications.

10. QTcF ≥ 470 msec calculated according to institutional guidelines, unless due tounderlying bundle branch block and/or pacemaker and with approval of themedical monitor.

11. Known moderate to severe and clinically significant chronic obstructivepulmonary disease, interstitial lung disease and/or pulmonary fibrosis (e.g.,requiring home oxygen therapy).

12. Pregnancy and/or lactation.

13. Major surgery (excluding placement of vascular access) within 4 weeks prior to firstdose of CTX-712.

14. History of allogeneic organ transplantation (excluding cornea).

15. History of allogenic hematopoietic stem cell transplantation within 6 months ofplanned study treatment initiation and/or graft-versus host disease grade ≥ 1following allogenic hematopoietic stem cell transplantation.

16. History of or chimeric antigen receptor T-cell therapy or other modified T celltherapy.

17. Active, uncontrolled bacterial, fungal, or viral infection, including hepatitis Bvirus, hepatitis C virus, known human immunodeficiency virus, or acquiredimmunodeficiency syndrome related illness. Infections controlled with oralanti-infective agents, including prophylactic treatments, are allowed. Patient mustbe viral load negative.

18. Psychological, familial, sociological, or geographical conditions that do not permitcompliance with the protocol and/or follow-up procedures outlined in the protocol.