Dose Escalation and Expansion Study to Evaluate the Safety, PK, PD and Efficacy of ZE46-0134 in Adults With FLT3 Mutated or Spliceosome Mutated Relapsed or Refractory Acute Myeloid Leukemia

NCT06366789 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: ZE46-0134-0002CT-2024-CTN-00161-1
• Study Type: interventional
• Target: 150
• Locations: 4 countries
• Sites: 23

Brief Summary

This is a clinical study aiming to assess pharmacokinetics, pharmacodynamics and preliminary efficacy of ZE46-0134 in patients with FLT3 and spliceosome mutated Relapsed or Refractory Acute Myeloid Leukemia

Conditions

AML With Gene Mutations

Outcome Measures

Primary Outcomes (1)

• The incidence of DLTs

  To determine the maximum tolerated dose or biologically effective dose of ZE46-0134 in adults with FLT3 and spliceosome mutated relapsed and refractory AML.

  From baseline to the End of Treatment (EOT) (Max 24 cycles, 28 days each)

Secondary Outcomes (12)

• Incidence of AE/SAE

  From baseline to the EOT (Max 24 cycles, 28 days each)

• Incidence of clinically significant abnormal laboratory results

  From baseline to the EOT (Max 24 cycles, 28 days each)

• Incidence of abnormal clinically significant ECG results

  From baseline to the EOT (Max 24 cycles, 28 days each)

• Number of patients with AEs of Grade ≥ 3

  From baseline to the EOT (Max 24 cycles, 28 days each)

• Number of treatment-related deaths

  From baseline to the EOT (Max 24 cycles, 28 days each)

Other Outcomes (2)

• Proportion of patients who became FLT3 ITD and TKD undetectable

  During 6 Cycles of treatment (28 days each)

• Number of patients with Genomic or proteomic abnormalities

  From baseline to the EOT (Max 24 cycles, 28 days each)

Study Arms (18)

ZE46-0134 Dose Level -1

EXPERIMENTAL

Optional and would only be performed Dose Level 1 is poorly tolerated

Drug: ZE46-0134

ZE46-0134 Dose Level 1

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Dose Level 2

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Dose Level 3

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Dose Level 4

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Dose Level 5

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Selected dose 1

EXPERIMENTAL

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study and will not exceed a loading dose of 150 mg x 2 days and maintenance dose of 50 mg QD

Drug: ZE46-0134

ZE46-0134 Selected dose 2

EXPERIMENTAL

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study and will not exceed a loading dose of 150 mg x 2 days and maintenance dose of 50 mg QD

Drug: ZE46-0134

ZE46-0134 Dose Level 6

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Dose Level 7

EXPERIMENTAL

Drug: ZE46-0134

ZE46-0134 Dose Level 8

EXPERIMENTAL

Drug: ZE46-0134

ZE50-0134 (Group 2) Dose Level -1

EXPERIMENTAL

Optional and would only be performed Dose Level 1 is poorly tolerated

Drug: ZE46-0134

ZE50-0134 (Group 2) Dose Level 1

EXPERIMENTAL

Drug: ZE46-0134

ZE50-0134 (Group 2) Dose Level 2

EXPERIMENTAL

Drug: ZE46-0134

ZE50-0134 (Group 2) Dose Level 3

EXPERIMENTAL

Drug: ZE46-0134

ZE50-0134 (Group 2) Dose Level 4

EXPERIMENTAL

Drug: ZE46-0134

ZE50-0134 (Group 2) Selected dose 1

EXPERIMENTAL

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study.

Drug: ZE46-0134

ZE50-0134 (Group 2) Selected dose 2

EXPERIMENTAL

The doses used in Part 2 of the study will be determined based on the data from Part 1 of the study.

Drug: ZE46-0134

Interventions

ZE46-0134 DRUG

oral capsules QD

ZE46-0134 Dose Level -1; ZE46-0134 Dose Level 1; ZE46-0134 Dose Level 2; ZE46-0134 Dose Level 3; ZE46-0134 Dose Level 4; ZE46-0134 Dose Level 5; ZE46-0134 Dose Level 6; ZE46-0134 Dose Level 7; ZE46-0134 Dose Level 8; ZE46-0134 Selected dose 1; ZE46-0134 Selected dose 2; ZE50-0134 (Group 2) Dose Level -1; ZE50-0134 (Group 2) Dose Level 1; ZE50-0134 (Group 2) Dose Level 2; ZE50-0134 (Group 2) Dose Level 3; ZE50-0134 (Group 2) Dose Level 4; ZE50-0134 (Group 2) Selected dose 1; ZE50-0134 (Group 2) Selected dose 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
• Patient is ≥18 years of age at the time of obtaining informed consent.
• Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
• Group 1: Patient must have a confirmed FLT3-ITD or FLT3-TKD mutation by central laboratory testing. Group 2: Patient must have a documented SF3B1, SRSF2, U2AF1, or ZRSR2 pathogenic mutation by local lab sequencing.
• For Group 1 only: Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.
• Patients have a life expectancy of at least 3 months in the opinion of the Investigator.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Patient must meet the following criteria as indicated on the clinical laboratory tests:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)
• Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease
• Estimated glomerular filtration (eGFR) rate of \>50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Female patients:
• If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
• If of childbearing potential, must:
• i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.

You may not qualify if:

• Written Informed Consent must be obtained from the patient or legally authorized representative prior to any study-related procedures (including withdrawal of prohibited medication, if applicable).
• Patient is ≥18 years of age at the time of obtaining informed consent.
• Patient is refractory to or relapsed after first-line AML therapy (with or without HSCT).
• Patient must have a confirmed FLT3 ITD, TKD or ITD-F691L mutation documented within the past 90 days in absence of therapy or within the Screening period 28 days) prior to study drug administration on C1D1 if therapy has been given.
• Patients must have previously been treated with Gilteritinib with failure to stop disease progression, or not met the criteria for treatment with Gilteritinib in the opinion of the Investigator, or chosen not to have treatment with Gilteritinib for social reasons.
• Patients have a life expectancy of at least 3 months in the opinion of the Investigator.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
• Patient must meet the following criteria as indicated on the clinical laboratory tests:
• Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × upper limit of normal (ULN)
• Serum total bilirubin ≤1.5 × ULN unless due to Gilbert's disease
• Estimated glomerular filtration (eGFR) rate of \>50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
• Female patients:
• If of non-childbearing potential i.e., surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy) at least 6 weeks before the Screening visit or postmenopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause and a follicle-stimulating hormone (FSH) level consistent with postmenopausal status, per local laboratory guidelines), or
• If of childbearing potential, must:
• i. Have a negative serum pregnancy test at the Screening visit and urine pregnancy test on admission to the clinic on Day-1.

Sponsors & Collaborators

• Lomond Therapeutics Holdings, Inc.: lead

Study Sites (23)

University of California, Los Angeles

Los Angeles, California, 90095, United States

RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

The University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

University of Kansas

Lawrence, Kansas, 66160, United States

RECRUITING

University of Maryland

College Park, Maryland, 20742, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

University of North Carolina

Chapel Hill, North Carolina, 27514, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Oregon Health & Science University

Portland, Oregon, 97239, United States

RECRUITING

The University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

RECRUITING

Eastern Health - Box Hill Hospital

Melbourne, Victoria, 3128, Australia

RECRUITING

Linear Clinical Research Ltd

Perth, Western Australia, 6009, Australia

RECRUITING

Gachon University Gil Medical Center

Incheon, Gyeonggi-do, 21565, South Korea

NOT YET RECRUITING

Korea University Anam Hospital

Seoul, 02841, South Korea

NOT YET RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

NOT YET RECRUITING

The Catholic University of Korea Seoul St. Mary's Hospital

Seoul, 06591, South Korea

NOT YET RECRUITING

Taipei Medical University-Shuang Ho Hospital, Ministry of Health and Welfare

New Taipei City, 235041, Taiwan

NOT YET RECRUITING

China Medical University Hospital

Taichung, 404327, Taiwan

NOT YET RECRUITING

National Cheng Kung University Hospital

Tainan, 704302, Taiwan

NOT YET RECRUITING

Taichung Veterans General Hospital

Xitun, 407219, Taiwan

NOT YET RECRUITING

Study Officials

• Carolyn Grove, Prof

  Linear Clinical Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kate Dokukina, PhD, MD

CONTACT

+38269728309; kdokukina@eileanther.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: dose escalation and dose optimization study

Study Record Dates

• First Submitted: April 5, 2024
• First Posted: April 16, 2024
• Study Start: May 29, 2024
• Primary Completion: January 1, 2026
• Study Completion (Estimated): December 1, 2027
• Last Updated: December 31, 2025

Record last verified: 2025-12

Locations

KR (4); US (12); TW (4); AU (3)