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

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia; Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: ZN-d5

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 Type: Interventional
• Enrollment (Estimated): 115
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals; Email: medicalaffairs@zentalis.com

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia
      • Terminated
      • Site 2708
    • Liverpool, New South Wales, Australia
      • Terminated
      • Site 2704
  • South Australia
    • Kurralta Park, South Australia, Australia
      • Terminated
      • Site 2710
  • Tasmania
    • Hobart, Tasmania, Australia
      • Terminated
      • Site 2709
• Bulgaria
  • Sofia, Bulgaria
    • Terminated
    • Site 1202
  • Varna, Bulgaria
    • Terminated
    • Site 1201
• Croatia
  • Zagreb, Croatia
    • Recruiting
    • Site 3201
• Korea, Republic of
  • Pusan, Korea, Republic of
    • Terminated
    • Site 2901
  • Seoul, Korea, Republic of
    • Terminated
    • Site 2903
• Poland
  • Gdansk, Poland
    • Terminated
    • Site 2403
• Spain
  • Barcelona, Spain
    • Active, not recruiting
    • Site 3001
  • Bilbao, Spain
    • Terminated
    • Site 3005
  • Valencia, Spain
    • Terminated
    • Site 3003
• Ukraine
  • Kiev, Ukraine
    • Terminated
    • Site 2001

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZN-d5 Single Agent Dose Escalation - NHL; Non-Hodgkin Lymphoma	Drug: ZN-d5; Oral agent; 25 mg or 100 mg formulation; Other Names: Study Drug
Experimental: ZN-d5 Single Agent Dose Escalation - AML; Acute Myeloid Leukemia	Drug: ZN-d5; Oral agent; 25 mg or 100 mg formulation; Other Names: Study Drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Dose Limiting Toxicities	Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.	Through completion of Cycle 1; 1 to 2 months.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
• Investigators: Study Director: K-Group Alpha Inc. /a subsidiary of Zentalis Pharmaceuticals, K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2020
• Primary Completion (Estimated): August 2, 2024
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: BCL-2 Inhibitors; BH3 mimetics
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Lymphoma; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: ZN-d5-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No