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).
Brief Title
Study of the ZN-d5 and 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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Acute Myeloid Leukemia (AML)
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
* 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
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
BCL-2 Inhibitors
Wee1 Inhibitors
AML
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT05682170
Org Class
Industry
Org Full Name
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Org Study Id
ZN-d5-004C
Overall Status
Terminated
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Observed Dose Limiting Toxicities (DLTs) in DLT evaluable subjects.
Outcome Measure
Observed dose limiting toxicities
Outcome Time Frame
At the end of Cycle 1 (each cycle is 28 days)
Outcome Measure
Incidence, severity, and relatedness of adverse events( AEs)
Outcome Time Frame
Through study completion, typically < 12 months
Secondary Outcomes
Outcome Description
The maximum plasma concentration (Cmax) of ZN-c3 (and its potential metabolites, as applicable) will be determined
Outcome Time Frame
Through study completion, typically <12 months
Outcome Measure
1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration
Outcome 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
Outcome Time Frame
Through study completion, typically < 12 months
Outcome Measure
2. To investigate the plasma PK of ZN-c3 when given as monotherapy - Area under the plasma concentration-time curve from 0 to 24h
Outcome 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
Outcome Time Frame
Through study completion, typically < 12 months
Outcome Measure
5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration
Outcome 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
Outcome Time Frame
Through study completion, typically < 12 months
Outcome Measure
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
Outcome Time Frame
Through study completion, typically < 12 months
Outcome Measure
Rate and duration or remission according to the European LeukemiaNet 2017 criteria
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Ioannis Mantzaris
Investigator Email
IMANTZAR@montefiore.org