Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis

Study Overview
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Brief Summary
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This is a single arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis.

Detailed Description
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A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis. The first part of the study is phase 1 dose-escalation and the second part will be phase 2.

Official Title
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A Single Arm, Open-Label, Phase 1/2 Study of ZN-d5 for the Treatment of Relapsed or Refractory Light Chain (AL) Amyloidosis

Conditions
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Amyloidosis, AL Amyloidosis

Intervention / Treatment
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* Drug: ZN-d5


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid. Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy; At least 3 months from hematopoietic stem cell transplantation or the shorter of 60 days or 5 half-lives for biologics, small molecules, or investigational drugs prior to starting treatment; Measurable disease defined by serum differential free light chain; Assessment of t(11,14) status by FISH; Eastern Cooperative Oncology Group performance status ≤2 ; History of organ involvement Adequate bone marrow function prior to first administration of study drug; Adequate organ function; Key Exclusion Criteria: Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis; Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria; Mayo 2012 Stage IV disease; Cardiac involvement exclusions apply to some subjects, including heart failure and cardiac arrhythmias. Prior treatment with other BCL-2 inhibitors;

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm<br>Subjects will receive ZN-d5 orally (PO), once (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. | Drug: ZN-d5<br>* ZN-d5 will be administered orally<br>* Other names: Study Drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Incidence and severity of adverse events (AEs), graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0 | 18 Months | 
| Dose limiting toxicities | Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects | 18 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK Parameter: Finding max concentration (Cmax) of ZN-d5 | Determine the maximum observed concentration (Cmax) of ZN-d5 collected in the plasma from subjects at different dose levels. | 48 months | 
| PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5 | The duration (in hours) it takes for ZN-d5 to reach the maximum concentration (or Cmax) collected in the plasma from subjects at different dose levels. | 48 months | 
| PK Parameter: Finding half-life of ZN-d5 | The time takes for half the drug concentration of ZN-d5 to be eliminated (Half-life) from the plasma that was collected from subjects at different dose levels | 48 months | 
| PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5 | The total exposure of ZN-d5 over time (AUC) from the plasma collected by the subject at different dose levels. | 48 months | 
| Assess the hematologic response to ZN-d5 | The number of Complete Response (CR), Very Good Partial Response (VGPR), Partial Response (PR), No Response (NR), Progressive Disease (PD) using the AL Amyloidosis Hematologic Response Criteria. | 48 months | 
| Duration and time to hematologic response to ZN-d5 | The rate of, duration of, and time to CR, modified Complete Response (mCR), CR+VGPR, and mCR+VGPR | 48 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BCL2 Inhibitor, RRAL, Amyloidosis, AL Amyloidosis, t(11;14), ZN-d5, Light Chain Amyloidosis, Light chain (AL) Amyloidosis