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)

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)

Study Overview

• Status: Recruiting
• Conditions: MDS; AML, Adult Recurrent
• Intervention / Treatment: Drug: LYT-200; Drug: Venetoclax; Drug: Azacitidine; Drug: Decitabine

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 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.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chris Korth; Phone Number: 617-982-2550; Email: clinicaltrials@puretechhealth.com
• Study Contact Backup: Name: Aleksandra Filipovic, MD, PhD.; Phone Number: 617-982-2550; Email: clinicaltrials@puretechhealth.com

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars-Sinai Medical Center
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine Medical Center
  • Florida
    • Miami, Florida, United States, 02114
      • Recruiting
      • Baptist Health South Florida-Miami Cancer Institute
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Healthcare-Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Mass. General Hospital-Harvard
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Rhode Island Hospital
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Recruiting
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single agent dose escalation; LYT-200 in relapsed/refractory AML or relapsed/refractory high-risk MDS, administered via IV infusion over 60 minutes every week.	Drug: LYT-200; monoclonal antibody (mAb), targeting galectin-9 protein
Experimental: Combination agent dose escalation; LYT-200 in relapsed/refractory AML or relapsed/refractory high-risk MDS, administered via IV infusion over 60 minutes every week, in combination with oral venetoclax Day 1, 100 mg, Day 2, 200mg, Day 3-28, 400 mg and/or azacitidine, 75 mg/m2 subcutaneously given for 7 days per cycle or decitabine 20 mg/m2 IV for 5 days per cycle.	Drug: LYT-200; monoclonal antibody (mAb), targeting galectin-9 protein; Drug: Venetoclax; Bcl-2 inhibitor; Drug: Azacitidine; Hypomethylating agent; Drug: Decitabine; Hypomethylating agent

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-Drug Antibody formation	Assess the immunogenicity of LYT-200	approximately 1 year

Collaborators and Investigators

• Sponsor: PureTech
• Investigators: Study Director: Aleksandra Filipovic, MD, PhD., PureTech Health

Study record dates

Study Major Dates

• Study Start (Actual): December 12, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: March 30, 2023
• First Submitted That Met QC Criteria: April 12, 2023
• First Posted (Actual): April 25, 2023

Study Record Updates

• Last Update Posted (Estimated): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: MDS; Immuno-oncology; AML Recurrent; AML Relapsed; AML Refractory; Hematological Cancer; Gal-9; MDS High Risk
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Leukemia; Leukemia, Myeloid; Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Venetoclax; Azacitidine
• Other Study ID Numbers: LYT-200-2022-02

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No