Clinical trial NCT05682170: Study of the ZN-d5 and ZN-c3 in Subjects With Acute Myeloid Leukemia (AML)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Acute Myeloid Leukemia (AML)
Keywords: BCL-2 Inhibitors
Wee1 Inhibitors
AML
Lead sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-01-12
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Observed dose limiting toxicities
timeFrame: At the end of Cycle 1 (each cycle is 28 days)
measure: Incidence, severity, and relatedness of adverse events( AEs)
timeFrame: Through study completion, typically < 12 months
Secondary outcomes:
measure: 1. To investigate the plasma PK of ZN-c3 when given as monotherapy - Maximum Plasma Concentration
timeFrame: Through study completion, typically <12 months
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
timeFrame: Through study completion, typically < 12 months
measure: 5. To investigate the plasma PK of ZN-c3 and ZN-d5 when given in combination - Maximum Plasma Concentration
timeFrame: Through study completion, typically < 12 months
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
timeFrame: Through study completion, typically < 12 months
measure: Rate and duration or remission according to the European LeukemiaNet 2017 criteria
timeFrame: Through study completion, typically < 12 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Bronx
country: United States
facility: Albert Einstein College of Medicine - Montefiore Medical Center
state: New York
city: New York
country: United States
facility: NYU Langone Health
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Columbus
country: United States
facility: James Cancer Hospital and Solove Research Institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Nashville
country: United States
facility: Tristar Bone Marrow Transplant
state: Tennessee
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Milwaukee
country: United States
facility: The Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: K-Group Alpha
name: K-Group Alpha, Inc. a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
role: STUDY_DIRECTOR
References: