Acute Myeloid Leukemia (AML)
Conditions
Keywords
BCL-2 Inhibitors, Wee1 Inhibitors, AML
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.
Interventions
DRUGZN-d5 ZN-c3
Oral agent
DRUGZN-c3
Oral agent
Sponsors
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Rate and duration or remission according to the European LeukemiaNet 2017 criteria | 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 | 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 |
| 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 |
Countries
United States
Outcome results
None listed