Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML)
- Registration Number
- NCT05682170
- Lead Sponsor
- K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 95
- 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.
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Acute Myeloid Leukemia ZN-c3 Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion Acute Myeloid Leukemia ZN-d5 ZN-c3 Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion
- Primary Outcome Measures
Name Time Method Observed dose limiting toxicities At the end of Cycle 1 (each cycle is 28 days) Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.
Incidence, severity, and relatedness of adverse events( AEs) Through study completion, typically < 12 months
- Secondary Outcome Measures
Name Time Method 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 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 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
Rate and duration or remission according to the European LeukemiaNet 2017 criteria Through study completion, typically < 12 months 1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration Through study completion, typically <12 months The maximum plasma concentration (Cmax) of ZN-c3 (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 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
Trial Locations
- Locations (13)
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
University of California San Francisco
🇺🇸San Francisco, California, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Albert Einstein College of Medicine - Montefiore Medical Center
🇺🇸Bronx, New York, United States
NYU Langone Health
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, 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
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Tristar Bone Marrow Transplant
🇺🇸Nashville, Tennessee, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
The Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States