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

Primary Purpose

Acute Myeloid Leukemia (AML)

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ZN-d5 ZN-c3
ZN-c3
Sponsored by
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia (AML) focused on measuring BCL-2 Inhibitors, Wee1 Inhibitors, AML

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at BirminghamRecruiting
  • University of California San FranciscoRecruiting
  • Dana Farber Cancer InstituteRecruiting
  • NYU Langone HealthRecruiting
  • Memorial Sloan Kettering Cancer CenterRecruiting
  • James Cancer Hospital and Solove Research InstituteRecruiting
  • University of Texas MD Anderson Cancer CenterRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Acute Myeloid Leukemia

Arm Description

Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion

Outcomes

Primary Outcome Measures

Observed dose limiting toxicities
Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.
Incidence, severity, and relatedness of adverse events( AEs)

Secondary Outcome Measures

1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration
The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined
2. To investigate the plasma PK of ZN-c3 when given as monotherapy - Area under the plasma concentration-time curve from 0 to 24h
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
5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration
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
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
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
Rate and duration or remission according to the European LeukemiaNet 2017 criteria

Full Information

First Posted
December 19, 2022
Last Updated
July 31, 2023
Sponsor
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05682170
Brief Title
Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML)
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2022 (Actual)
Primary Completion Date
March 1, 2025 (Anticipated)
Study Completion Date
February 1, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia (AML)
Keywords
BCL-2 Inhibitors, Wee1 Inhibitors, AML

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
95 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Acute Myeloid Leukemia
Arm Type
Experimental
Arm Description
Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion
Intervention Type
Drug
Intervention Name(s)
ZN-d5 ZN-c3
Other Intervention Name(s)
Study Drug
Intervention Description
Oral agent
Intervention Type
Drug
Intervention Name(s)
ZN-c3
Other Intervention Name(s)
Study Drug
Intervention Description
Oral agent
Primary Outcome Measure Information:
Title
Observed dose limiting toxicities
Description
Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.
Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Title
Incidence, severity, and relatedness of adverse events( AEs)
Time Frame
Through study completion, typically < 12 months
Secondary Outcome Measure Information:
Title
1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration
Description
The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined
Time Frame
Through study completion, typically <12 months
Title
2. To investigate the plasma PK of ZN-c3 when given as monotherapy - Area under the plasma concentration-time curve from 0 to 24h
Description
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
Time Frame
Through study completion, typically < 12 months
Title
5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration
Description
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
Time Frame
Through study completion, typically < 12 months
Title
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
Description
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
Time Frame
Through study completion, typically < 12 months
Title
Rate and duration or remission according to the European LeukemiaNet 2017 criteria
Time Frame
Through study completion, typically < 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Email
medicalaffairs@zentalis.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Organizational Affiliation
K-Group Alpha
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pankit Vachhani, MD
Phone
205-975-7850
Email
pvachhani@uabmc.edu
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Smith, MD
Phone
415-353-2421
Email
Catherine.Smith@ucsf.edu
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eric Winer, MD
Phone
877-442-3324
Email
EricS_Winer@DFCI.HARVARD.EDU
Facility Name
NYU Langone Health
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohammad Abdul Hay, MD
Phone
646-501-4818
Email
maher.abdulhay@nyulangone.org
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Raajit Rampal, MD
Phone
212-639-2194
Email
rampalr@mskcc.org
Facility Name
James Cancer Hospital and Solove Research Institute
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Grieselhuber Grieselhuber, MD
Phone
614-366-1164
Email
Nicole.Grieselhuber@osumc.edu
Facility Name
University of Texas MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guillermo Garcia-Manero, MD
Phone
713-745-3428
Email
ggarciam@mdanderson.org

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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