A Phase 1 Study With LYT-200 in Patients With Relapsed/Refractory Acute Myeloid Leukemia (AML), or With Relapsed/Refractory, High-risk Myelodysplastic Syndrome (MDS)

A Phase 1 Open-label, Multi-center Study of the Safety, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 in Patients with Relapsed/Refractory Acute Myeloid Leukemia (AML), or with Relapsed/refractory, High-risk Myelodysplastic Syndrome (MDS)

This is an open-label, non-randomized, multi-center, Phase 1, dose escalation study in patients with AML relapsed/refractory to at least one line of prior therapy, with or without an allogeneic stem cell transplant, or in patients with a documented diagnosis of relapsed/refractory, high-risk myelodysplastic syndrome (MDS) post at least one line of treatment and for whom no standard therapy that may provide clinical benefit is available. The 4+2 algorithm-based dose-escalation design will be used to help identify the recommended Phase 2 dose (RP2D). Single agent LYT-200 and in combination with venetoclax and/or hypomethylating agents (HMA) safety and tolerability evaluation is the primary study endpoint, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 single agent and in combination with venetoclax and/or HMAs are key secondary study endpoints.

Eligibility Criteria:
Inclusion Criteria:

* Patients ≥ 18 years of age at the time of obtaining informed consent.
* Patients with morphologically documented primary or secondary AML by the World Health Organization(WHO) criteria, whose disease is relapsed/refractory to at least one line of prior therapy, with or without an allogeneic stem cell transplant and for whom no standard therapy that may provide clinical benefit is available or for patients who decline available standard of care.
* Patients with a documented diagnosis of high-risk myelodysplastic syndrome (MDS), whose disease is relapsed/refractory, post at least one line of treatment based on the revised International Prognostic Scoring System (IPSS-R) and for whom no standard therapy that may provide clinical benefit is available
* Patients are able and willing to comply with study procedures as per protocol, including bone marrowbiopsies.
* Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
* Patient must meet the following criteria as indicated on the clinical laboratory tests:

oWhite blood cell (WBC) count at the time of the first dose of \< 25,000/uL. oAspartate aminotransferase or alanine aminotransferase ≤ 3 × upper limit of normal (ULN; ≤ 5.0× ULN if considered to be due to leukemic involvement). oTotal bilirubin ≤ 2 × ULN (≤ 3 × ULN if considered to be due to leukemic involvement orGilbert's syndrome). oCreatinine clearance of ≥ 60 mL/min.

Exclusion Criteria:

* Patient diagnosed with acute promyelocytic leukemia (APL).
* Patient has active malignant tumors other than AML/MDS
* Patient has had HSCT and meets any of the following: has undergone HSCT within the 6- month period prior to the first study dose; has ≥ Grade 2 persistent non-hematological toxicity related to the transplant donor lymphocytes infusion.
* Patient has active graft versus host disease (GVHD) and patients receiving immunosuppressive treatment for GVHD.
* Patient with symptomatic central nervous system (CNS) involvement of leukemia or other CNS diseases related to underlying and secondary effects of malignancy
* Patient has had major surgery within 4 weeks prior to the first study dose.
* Patient has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or patient with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or multigated acquisition (MUGA) scan performed within 3 months prior to study entry results in a left ventricular ejection fraction (LVEF) that is ≥ 45%.
* Patient has any condition which, in the Investigator's opinion, makes the patient unsuitable for study participation.