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

Acute Myeloid Leukemia (AML) Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05682170
• Other study ID #: ZN-d5-004C
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: December 1, 2022
• Est. completion date: February 1, 2026

Study information

• Verified date: January 2024
• Source: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
• Contact: K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharma
• Email: medicalaffairs[@]zentalis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 95
• Est. completion date: February 1, 2026
• Est. primary completion date: March 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• ZN-d5 ZN-c3
Oral agent
• ZN-c3
Oral agent

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Albert Einstein College of Medicine - Montefiore Medical Center	Bronx	New York
United States	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	James Cancer Hospital and Solove Research Institute	Columbus	Ohio
United States	University of Texas MD Anderson Cancer Center	Houston	Texas
United States	The Medical College of Wisconsin	Milwaukee	Wisconsin
United States	University of Minnesota	Minneapolis	Minnesota
United States	Tristar Bone Marrow Transplant	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	NYU Langone Health	New York	New York
United States	Oregon Health and Science University	Portland	Oregon
United States	University of California San Francisco	San Francisco	California

Sponsors (1)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed dose limiting toxicities	Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.	At the end of Cycle 1 (each cycle is 28 days)
Primary	Incidence, severity, and relatedness of adverse events( AEs)		Through study completion, typically < 12 months
Secondary	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	Through study completion, typically <12 months
Secondary	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	Through study completion, typically < 12 months
Secondary	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	Through study completion, typically < 12 months
Secondary	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	Through study completion, typically < 12 months
Secondary	Rate and duration or remission according to the European LeukemiaNet 2017 criteria		Through study completion, typically < 12 months