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Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT05682170
Recruitment Status : Recruiting
First Posted : January 12, 2023
Last Update Posted : May 10, 2024
Sponsor:
Information provided by (Responsible Party):
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Study Description
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Brief Summary:
A Phase 1/2 dose escalation study of BCL-2 Inhibitor ZN-d5 and the Wee1 Inhibitor ZN-c3 in Subjects with Acute Myeloid Leukemia (AML).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia (AML) Drug: ZN-d5 ZN-c3 Drug: ZN-c3 Phase 1 Phase 2

Detailed Description:
This is an open-label multicenter Phase 1/2 dose escalation study, evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2 inhibitor ZN-d5 and Wee1 inhibitor ZN-c3 in subjects with AML.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 95 participants
Allocation: N/A
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2 Dose Escalation Study of the BCL-2 Inhibitor ZN-d5 and the WEE1 Inhibitor ZN-c3 in Subjects With Acute Myeloid Leukemia
Actual Study Start Date : December 1, 2022
Estimated Primary Completion Date : March 1, 2025
Estimated Study Completion Date : February 1, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Acute Myeloid Leukemia

Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination

Phase 2: Dose Expansion

 Drug: ZN-d5 ZN-c3
Oral agent
Other Name: Study Drug

Drug: ZN-c3
Oral agent
Other Name: Study Drug


Outcome Measures
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Primary Outcome Measures :
  1. Observed dose limiting toxicities [ Time Frame: At the end of Cycle 1 (each cycle is 28 days) ]
    Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.

  2. Incidence, severity, and relatedness of adverse events( AEs) [ Time Frame: Through study completion, typically < 12 months ]

Secondary Outcome Measures :
  1. 1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration [ Time Frame: Through study completion, typically <12 months ]
    The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined

  2. 2. To investigate the plasma PK of ZN-c3 when given as monotherapy - Area under the plasma concentration-time curve from 0 to 24h [ Time Frame: Through study completion, typically < 12 months ]
    Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) will be determined

  3. 5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration [ Time Frame: Through study completion, typically < 12 months ]
    The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) and ZN-d5 (and its potential metabolites, as applicable) will be determined

  4. 6. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Area under the plasma concentration-time curve from 0 to 24h [ Time Frame: Through study completion, typically < 12 months ]
    Area under the plasma concentration-time curve from 0 to 24h [AUC0-24h] of ZN-c3 (and its potential metabolites, as applicable) and ZN-d5 (and its potential metabolites, as applicable) will be determined

  5. Rate and duration or remission according to the European LeukemiaNet 2017 criteria [ Time Frame: Through study completion, typically < 12 months ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults with AML (including secondary or therapy-related), relapsed from or refractory to one or more prior lines of therapy, which may include venetoclax except in Expansion Cohort A
  • ECOG performance status score ≤2.
  • Projected life expectancy of at least 12 weeks.
  • Estimated glomerular filtration rate ≥60 mL/min
  • Women of childbearing potential must not be pregnant and must use effective birth control during the study and for 6 months after the last dose of study drugs.
  • Men must agree to use a condom when having intercourse during the study and for 3 months after the last dose of study drugs.

Exclusion Criteria:

  • Known active CNS involvement
  • Diagnosis of acute promyelocytic leukemia.
  • Peripheral blast count of >25 × 109/L (cytoreduction permitted).
  • Adequate washout from prior therapy including hematopoietic stem cell transplant and recovery from prior treatment-related toxicities to Grade 2 or lower
  • Significant cardiovascular disease
  • Corrected QT interval (QTc) of >480 msec
  • Active hepatitis B or hepatitis C infection
  • Concurrent treatment with strong CYP3A inhibitors or strong or moderate CYP3A inducers
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05682170


Contacts
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Contact: K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. medicalaffairs@zentalis.com

Locations
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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35233
Contact: Pankit Vachhani, MD    205-975-7850    pvachhani@uabmc.edu   
United States, California
University of California San Francisco Recruiting
San Francisco, California, United States, 94110
Contact: Catherine Smith, MD    415-353-2421    Catherine.Smith@ucsf.edu   
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact: Eric Winer, MD    877-442-3324    EricS_Winer@DFCI.HARVARD.EDU   
United States, Minnesota
University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 53792
Contact: Mark Juckett, MD    612-676-4200    juck0001@umn.edu   
United States, New York
Albert Einstein College of Medicine - Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Ioannis Mantzaris, MD    718-920-4826    IMANTZAR@montefiore.org   
NYU Langone Health Recruiting
New York, New York, United States, 10016
Contact: Mohammad Abdul Hay, MD    646-501-4818    maher.abdulhay@nyulangone.org   
Memorial Sloan Kettering Cancer Center Recruiting
New York, New York, United States, 10065
Contact: Raajit Rampal, MD    212-639-2194    rampalr@mskcc.org   
United States, North Carolina
University of North Carolina at Chapel Hill Recruiting
Chapel Hill, North Carolina, United States, 27514
Contact: Joshua Zeidner, MD    919-966-4432    joshua_zeidner@med.unc.edu   
United States, Ohio
James Cancer Hospital and Solove Research Institute Recruiting
Columbus, Ohio, United States, 43210
Contact: Grieselhuber Grieselhuber, MD    614-366-1164    Nicole.Grieselhuber@osumc.edu   
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Ronan Swords, MD    503-494-9014    swords@ohsu.com   
United States, Tennessee
Tristar Bone Marrow Transplant Recruiting
Nashville, Tennessee, United States, 37203
Contact: Stephen Strickland, MD    615-329-7274    XOResearchCentralScreening@USONCOLOGY.COM   
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Guillermo Garcia-Manero, MD    713-745-3428    ggarciam@mdanderson.org   
United States, Wisconsin
The Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States, 53226
Contact: Guru Subramanian Guru Murthy, MD    414-805-8900    cccto@mcw.edu   
Sponsors and Collaborators
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Investigators
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Study Director: K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. K-Group Alpha
More Information
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Responsible Party: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05682170    
Other Study ID Numbers: ZN-d5-004C
First Posted: January 12, 2023    Key Record Dates
Last Update Posted: May 10, 2024
Last Verified: January 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.:
BCL-2 Inhibitors
Wee1 Inhibitors
AML
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
 Neoplasms by Histologic Type
Neoplasms
Hematologic Diseases