Phase 1 First in Human Study of ZN-d5 as a Single Agent
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 115
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
- 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 Observed Dose Limiting Toxicities Through completion of Cycle 1; 1 to 2 months. Observed Dose Limiting Toxicities (DLTs) in DLT-evaluable subjects.
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.
- Secondary Outcome Measures
Name Time Method 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.
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).
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 2001
🇺🇦Kiev, Ukraine
Site 2403
🇵🇱Gdansk, Poland
Site 3001
🇪🇸Barcelona, Spain
Site 3005
🇪🇸Bilbao, Spain
Site 2708
🇦🇺Darlinghurst, New South Wales, Australia
Site 3003
🇪🇸Valencia, Spain
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