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

Amyloidosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05199337
• Other study ID #: ZN-d5-003
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: November 30, 2021
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 135
• Est. completion date: December 2025
• Est. primary completion date: May 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• AL Amyloidosis
• Amyloidosis
• Immunoglobulin Light-chain Amyloidosis

Intervention

Drug:
• ZN-d5
ZN-d5 will be administered orally

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Cyprus,  Greece,  Israel,  Italy,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	To assess potential biomarker of ZN-d5	The number of peripheral B-Cells from blood tests	48 months
Primary	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
Primary	Dose limiting toxicities	Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects	18 Months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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