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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: AL Amyloidosis; Amyloidosis
• Intervention / Treatment: Drug: ZN-d5

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 135
• Phase: Phase 2; Phase 1

Contacts and Locations

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

Study Locations

• Australia
  • New South Wales
    • Westmead, New South Wales, Australia, 2145
      • Blackwater (Westmead) Hospital
  • Queensland
    • Brisbane, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Western Australia
    • Nedlands, Western Australia, Australia
      • Sir Charles Gairdner Hospital
• Cyprus
  • Nicosia, Cyprus
    • Bank of Cyprus Hospital
• Greece
  • Athens, Greece, 115 28
    • National and Kapodistrian University of Athens
• Israel
  • Haifa, Israel, 3109601
    • Rambam Hospital
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Tel Aviv, Israel
    • Sheba Medical Center
  • Tel Aviv, Israel
    • Tel Aviv Sourasky Medical Center PPDS
• Italy
  • Bologna, Italy
    • IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi
  • Pavia, Italy
    • Fondazione I.R.C.C.S. Policlinico San Matteo
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clínic de Barcelona
  • Salamanca, Spain
    • Clinico de Salamanca
  • Badalona
    • Barcelona, Badalona, Spain
      • ICO Badalona-H.U. Germans Trias i Pujol
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clinico Universitario Virgen de la Arrixaca
• United States
  • California
    • Los Angeles, California, United States, 90089
      • University of Southern California
  • Colorado
    • Denver, Colorado, United States, 80218
      • Colorado Blood Cancer Institute
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Missouri
    • Saint Louis, Missouri, United States, 63130
      • Washington University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Diagnosis of AL amyloidosis based on histopathology, the presence of characteristic appearance on electron microscopy, or mass spectrometry typing of amyloid.
2. Prior AL amyloidosis treatment and has received at least one, but no more than three lines of prior therapy;
3. 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;
4. Measurable disease defined by serum differential free light chain;
5. Assessment of t(11,14) status by FISH;
6. Eastern Cooperative Oncology Group performance status ≤2 ;
7. History of organ involvement
8. Adequate bone marrow function prior to first administration of study drug;
9. Adequate organ function;

Key Exclusion Criteria:

1. Presence of non-AL amyloidosis, including wild-type or mutated ATTR amyloidosis;
2. Diagnosis of multiple myeloma according to the 2014 International Myeloma Working Group diagnostic criteria;
3. Mayo 2012 Stage IV disease;
4. Cardiac involvement exclusions apply to some subjects, including heart failure and cardiac arrhythmias.
5. Prior treatment with other BCL-2 inhibitors;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; 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; ZN-d5 will be administered orally; Other Names: Study Drug

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess potential biomarker of ZN-d5	The number of peripheral B-Cells from blood tests	48 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 30, 2021
• Primary Completion (Estimated): May 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: January 9, 2022
• First Submitted That Met QC Criteria: January 18, 2022
• First Posted (Actual): January 20, 2022

Study Record Updates

• Last Update Posted (Actual): 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: Light Chain Amyloidosis; Amyloidosis; AL Amyloidosis; RRAL; BCL2 Inhibitor; t(11;14); ZN-d5; Light chain (AL) Amyloidosis
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Paraproteinemias; Proteostasis Deficiencies; Neoplasms, Plasma Cell; Immunoglobulin Light-chain Amyloidosis; Amyloidosis
• Other Study ID Numbers: ZN-d5-003

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