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

Sponsor

K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05682170

Collaborator

(none)

Enrollment

Locations

Arm

Anticipated Duration (Months)

31.7

Patients Per Site

0.8

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia (AML)	Drug: ZN-d5 ZN-c3 Drug: ZN-c3	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

95 participants

Allocation:

N/A

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Mar 1, 2025

Anticipated Study Completion Date :

Feb 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Acute Myeloid Leukemia Phase 1: Dose Escalation- c3 monotherapy and d5+c3 combination Phase 2: Dose Expansion- cohort A and cohort B	Drug: ZN-d5 ZN-c3 Oral agent Other Names: Study Drug Drug: ZN-c3 Oral agent Other Names: Study Drug

Arm

Intervention/Treatment

Experimental: Acute Myeloid Leukemia

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

Drug: ZN-d5 ZN-c3

Oral agent

Other Names:

Study Drug

Drug: ZN-c3

Oral agent

Other Names:

Study Drug

Outcome Measures

Primary Outcome Measures

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

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
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
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
Rate and duration or remission according to the European LeukemiaNet 2017 criteria [Through study completion, typically < 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigative Site 0108	Birmingham	Alabama	United States	35233
2	Site 0266	San Francisco	California	United States	94110
3	Site 0105	New York	New York	United States	10065