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

NCT05682170 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: ZN-d5-004C
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 13

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).

Conditions

Acute Myeloid Leukemia (AML)

Keywords

BCL-2 Inhibitors; Wee1 Inhibitors; AML

Outcome Measures

Primary Outcomes (2)

• Observed dose limiting toxicities

  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)

  Through study completion, typically < 12 months

Secondary Outcomes (5)

• 1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration

  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

  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

  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

  Through study completion, typically < 12 months

• Rate and duration or remission according to the European LeukemiaNet 2017 criteria

  Through study completion, typically < 12 months

Study Arms (1)

Acute Myeloid Leukemia

EXPERIMENTAL

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

Drug: ZN-d5 ZN-c3; Drug: ZN-c3

Interventions

ZN-d5 ZN-c3 DRUG

Oral agent

Also known as: Study Drug

Acute Myeloid Leukemia

ZN-c3 DRUG

Oral agent

Also known as: Study Drug

Acute Myeloid Leukemia

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (13)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

University of California San Francisco

San Francisco, California, 94110, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Minnesota

Minneapolis, Minnesota, 53792, United States

Location

NYU Langone Health

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Albert Einstein College of Medicine - Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Tristar Bone Marrow Transplant

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Drug Evaluation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Drug Development; Investigative Techniques; Evaluation Studies as Topic

Study Officials

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

  K-Group Alpha

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: January 12, 2023
• Study Start: December 1, 2022
• Primary Completion: July 2, 2024
• Study Completion: July 26, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (13)