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

September 12, 2024 updated by: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

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

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).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • California
      • San Francisco, California, United States, 94110
        • University of California San Francisco
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana Farber Cancer Institute
    • Minnesota
      • Minneapolis, Minnesota, United States, 53792
        • University of Minnesota
    • New York
      • Bronx, New York, United States, 10467
        • Albert Einstein College of Medicine - Montefiore Medical Center
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • NYU Langone Health
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • University of North Carolina at Chapel Hill
    • Ohio
      • Columbus, Ohio, United States, 43210
        • James Cancer Hospital and Solove Research Institute
    • Oregon
      • Portland, Oregon, United States, 97239
        • Oregon Health and Science University
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • TriStar Bone Marrow Transplant
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas MD Anderson Cancer Center
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • The Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Study Drug
Drug: ZN-c3
Oral agent
Other Names:
  • Study Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
At the end of Cycle 1 (each cycle is 28 days)
Incidence, severity, and relatedness of adverse events( AEs)
Time Frame: Through study completion, typically < 12 months
Through study completion, typically < 12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Through study completion, typically <12 months
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
Through study completion, typically < 12 months
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
Through study completion, typically < 12 months
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
Through study completion, typically < 12 months
Rate and duration or remission according to the European LeukemiaNet 2017 criteria
Time Frame: Through study completion, typically < 12 months
Through study completion, typically < 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Investigators

  • Study Director: K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc., K-Group Alpha

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2022

Primary Completion (Actual)

July 2, 2024

Study Completion (Actual)

July 26, 2024

Study Registration Dates

First Submitted

December 19, 2022

First Submitted That Met QC Criteria

January 3, 2023

First Posted (Actual)

January 12, 2023

Study Record Updates

Last Update Posted (Actual)

September 19, 2024

Last Update Submitted That Met QC Criteria

September 12, 2024

Last Verified

September 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZN-d5-004C

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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