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)

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

Detailed Description
-----------------
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 safety and tolerability is the primary study endpoint, Pharmacokinetics (PK), and Anti-tumor Activity of LYT- 200 are key secondary study endpoints.

Official Title
-----------------
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)

Conditions
-----------------
AML, Adult Recurrent, MDS

Intervention / Treatment
-----------------
* Drug: LYT-200


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: A Phase 1 open-label, multi-center study. The 4+2 algorithm-based dose-escalation design will be used to help identify the recommended Phase 2 dose (RP2D). Up to 6 patients per treatment Cohorts 1-5 will receive infusions of LYT-200 every week (QW).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Single agent dose escalation<br>LYT-200 in relapsed/refractory AML or relapsed/refractory high-risk MDS, administered via IV infusion over 60 minutes every week. | Drug: LYT-200<br>* monoclonal antibody (mAb), targeting galectin-9 protein<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Treatment-Emergent Adverse Events [Safety and RP2D determination] | Evaluation of safety parameters including treatment emergent adverse events as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, ECG, ECHO/MUGA, ECOG status | approximately 1 year | 
| Incidence of Dose Limiting Toxicities [Tolerability and RP2D determination] | Evaluation of tolerability parameters including dose limiting toxicities as detected by hematology, chemistry, coagulation safety labs, physical exams, vital signs, ECG, ECHO/MUGA, ECOG status | approximately 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of disease responses, time-to-event endpoints, hematological improvements | Evaluate preliminary efficacy of LYT- 200 as a single agent in AML and MDS | approximately 1 year | 
| Pharmacokinetic (PK) profile of LYT-200_Area Under the Curve (AUC) | Characterize the PK profile of LYT-200 | approximately 1 year | 
| Pharmacokinetic (PK) profile of LYT-200_Concentration Max (CMax) | Characterize the PK profile of LYT-200 | approximately 1 year | 
| Pharmacokinetic (PK) profile of LYT-200_Time to Reach CMax (TMax) | Characterize the PK profile of LYT-200 | approximately 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
AML Recurrent, AML Relapsed, AML Refractory, Hematological Cancer, Gal-9, Immuno-oncology, MDS, MDS High Risk