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

K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.39 enrolled

Overview

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

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Acute Myeloid Leukemia Non Hodgkin Lymphoma

Interventions

ZN-d5DRUG

Oral agent; 25 mg or 100 mg formulation

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

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

Outcomes

Primary Outcomes

Observed Dose Limiting Toxicities

Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.

Time frame: 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.

Time frame: Through study completion, typically < 12 months

Secondary Outcomes

Pharmacokinetic parameters for ZN-d5 - Cmax

Characterize the Pharmacokinetics of ZN-d5 in subjects with NHL and AML using peak plasma concentration (Cmax).

Time frame: 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).

Time frame: 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).

Time frame: 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.

Data from ClinicalTrials.gov

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