Phase 1 First in Human Study of ZN-d5 as a Single Agent

Acute Myeloid Leukemia Clinical Trial

Official title:

Phase 1 First in Human Dose-Escalation Study of ZN-d5 as a Single Agent in Subjects With Non-Hodgkin Lymphoma or Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04500587
• Other study ID #: ZN-d5-001
• Status: Recruiting
• Phase: Phase 1
• Start date: October 13, 2020
• Est. completion date: January 2025

Study information

• Verified date: March 2024
• Source: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
• Contact: K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals
• Email: medicalaffairs[@]zentalis.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Phase 1 dose escalation study of ZN-d5 in subjects with relapsed or refractory non-Hodgkin lymphoma (NHL) or acute myeloid leukemia (AML).

Description:

This is an open-label multicenter Phase 1 dose escalation study evaluating the safety, tolerability, clinical activity, pharmacokinetics and pharmacodynamics of the novel BCL-2 inhibitor ZN-d5 in subjects with (NHL) or (AML) in order to determine the recommended phase 2 dose of ZN-d5.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 115
• Est. completion date: January 2025
• Est. primary completion date: August 2, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

NHL: relapsed or refractory NHL including DLBCL, FL, MZL, MCL, LCL, LPL and PTC

• Subjects must have received at least 2 prior lines of therapy and have either failed or not be eligible for any available therapies expected to provide clinical benefit and have measurable disease. AML: Primary, secondary, or treatment-related AML, relapsed or refractory to prior therapy, which may include failure of one cycle of induction therapy.
• White blood cell count < 25 × 109/L. Cytoreduction prior to treatment is acceptable.
• Subjects may not be pregnant and must agree to use an effective method of contraception.
• Eastern Cooperative Oncology Group performance status = 2.
• Estimated life expectancy of at least 12 weeks.
• Adequate hematologic and organ function, including creatinine clearance = 60 mL/min.

Key Exclusion Criteria:

• Recent interventions including major surgery, radiation therapy, stem cell transplant.
• Treatment with anti-neoplastic agents with 5 half-lives.
• Significant unresolved toxicity from prior treatments including active GVHD.
• Active central nervous system disease.
• Clinically substantial myocardial impairment.
• Prior therapy with venetoclax.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non Hodgkin Lymphoma

Intervention

Drug:
• ZN-d5
Oral agent; 25 mg or 100 mg formulation

Locations

Country	Name	City	State
Australia	Site 2708	Darlinghurst	New South Wales
Australia	Site 2709	Hobart	Tasmania
Australia	Site 2710	Kurralta Park	South Australia
Australia	Site 2704	Liverpool	New South Wales
Bulgaria	Site 1202	Sofia
Bulgaria	Site 1201	Varna
Croatia	Site 3201	Zagreb
Korea, Republic of	Site 2901	Pusan
Korea, Republic of	Site 2903	Seoul
Poland	Site 2403	Gdansk
Spain	Site 3001	Barcelona
Spain	Site 3005	Bilbao
Spain	Site 3003	Valencia
Ukraine	Site 2001	Kiev

Sponsors (1)

Lead Sponsor	Collaborator
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

Australia,  Bulgaria,  Croatia,  Korea, Republic of,  Poland,  Spain,  Ukraine, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed Dose Limiting Toxicities	Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.	Through completion of Cycle 1; 1 to 2 months.
Primary	Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0	Safety profile of ZN-d5.	Through study completion, typically < 12 months
Secondary	Pharmacokinetic parameters for ZN-d5 - Cmax	Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax).	approximately 6 months
Secondary	Pharmacokinetic parameters for ZN-d5 - Tmax	Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using the time to maximum plasma concentration (Tmax).	approximately 6 months
Secondary	Pharmacokinetic parameters for ZN-d5 - AUC	Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using area under the plasma concentration versus time curve (AUC).	approximately 6 months
Secondary	For NHL, evaluate response according to the Lugano 2014 classification	Evaluate response according to the Lugano 2014 classification for NHL subjects. The Lugano Classification is based on a 5-point scale for scoring of metabolically active lesions detected by PET-CT in FDG-avid lymphomas, and lesion size for non-FDG-avid tumors. A complete metabolic response would require a score of 1 or 2 on target and non-target lesions and the spleen for high-risk disease, and a score of 1,2, or 3 for low-risk disease. A partial response, no response, or progression would require a score of 4 or 5 for low-risk disease, and a score of 3, 4, or 5 for high-risk disease.	Through study completion, typically < 12 months
Secondary	For AML, remission rate based on European LeukemiaNet 2017 criteria	Evaluate remission rate according to the European LeukemiaNet 2017 criteria (Overall Response Rate (ORR) defined as Complete Remission (CR) + CR with incomplete hematologic recovery (CRi) + Morphologic Leukemia-Free State (MLFS) + Partial Remission (PR)) for AML subjects.	Through study completion, typically < 12 months
Secondary	For AML, duration of remission based on European LeukemiaNet 2017 criteria	Evaluate duration of remission according to the European LeukemiaNet 2017 criteria.	Through study completion, typically < 12 months