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

Phase 1

Recruiting

• Conditions: Non Hodgkin Lymphoma; Acute Myeloid Leukemia
• Interventions: Drug: ZN-d5

• Registration Number: NCT04500587
• Lead Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Brief Summary

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

Detailed 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.

Study Timeline

• Study First Submitted: 2020-07-30
• Study First Submitted QC: 2020-08-03
• Study First Posted: 2020-08-05
• Study Start: 2020-10-13
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05
• Primary Completion: 2024-08-02
• Study Completion: 2025-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 115

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ZN-d5 Single Agent Dose Escalation - NHL	ZN-d5	Non-Hodgkin Lymphoma
ZN-d5 Single Agent Dose Escalation - AML	ZN-d5	Acute Myeloid Leukemia

Primary Outcome Measures

Name	Time	Method
Incidence and severity of AEs, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, v 5.0	Through study completion, typically < 12 months	Safety profile of ZN-d5.
Observed Dose Limiting Toxicities	Through completion of Cycle 1; 1 to 2 months.	Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.

Secondary Outcome Measures

Name	Time	Method
For AML, duration of remission based on European LeukemiaNet 2017 criteria	Through study completion, typically < 12 months	Evaluate duration of remission according to the European LeukemiaNet 2017 criteria.
Pharmacokinetic parameters for ZN-d5 - Cmax	approximately 6 months	Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax).
For AML, remission rate based on European LeukemiaNet 2017 criteria	Through study completion, typically < 12 months	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.
Pharmacokinetic parameters for ZN-d5 - Tmax	approximately 6 months	Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using the time to maximum plasma concentration (Tmax).
Pharmacokinetic parameters for ZN-d5 - AUC	approximately 6 months	Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using area under the plasma concentration versus time curve (AUC).
For NHL, evaluate response according to the Lugano 2014 classification	Through study completion, typically < 12 months	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.

Trial Locations

Locations (14)

Site 2708; 🇦🇺 Darlinghurst, New South Wales, Australia

Site 2704; 🇦🇺 Liverpool, New South Wales, Australia

Site 2710; 🇦🇺 Kurralta Park, South Australia, Australia

Site 2709; 🇦🇺 Hobart, Tasmania, Australia

Site 1202; 🇧🇬 Sofia, Bulgaria

Site 1201; 🇧🇬 Varna, Bulgaria

Site 3201; 🇭🇷 Zagreb, Croatia

Site 2901; 🇰🇷 Pusan, Korea, Republic of

Site 2903; 🇰🇷 Seoul, Korea, Republic of

Site 2403; 🇵🇱 Gdansk, Poland

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