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

Sponsor

K-Group Alpha, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05199337

Collaborator

(none)

135

Enrollment

Locations

Arm

Anticipated Duration (Months)

8.4

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
Amyloidosis AL Amyloidosis	Drug: ZN-d5	Phase 1/Phase 2

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 Design

Study Type:

Interventional

Anticipated Enrollment :

135 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Nov 30, 2021

Anticipated Primary Completion Date :

May 1, 2025

Anticipated Study Completion Date :

Dec 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment Arm Subjects will receive ZN-d5 orally (PO), once daily (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

Arm

Intervention/Treatment

Experimental: Treatment Arm

Subjects will receive ZN-d5 orally (PO), once daily (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

Outcome Measures

Primary Outcome Measures

Safety and Tolerability [18 Months]
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
Dose limiting toxicities [18 Months]
Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects

Secondary Outcome Measures

PK Parameter: Finding max concentration (Cmax) of ZN-d5 [48 months]
Determine the maximum observed concentration (Cmax) of ZN-d5 collected in the plasma from subjects at different dose levels.
PK Parameter: Finding time to maximum concentration (Tmax) of ZN-d5 [48 months]
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.
PK Parameter: Finding half-life of ZN-d5 [48 months]
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
PK Parameter: Finding the Area Under the Curve (AUC) of ZN-d5 [48 months]
The total exposure of ZN-d5 over time (AUC) from the plasma collected by the subject at different dose levels.
Assess the hematologic response to ZN-d5 [48 months]
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.
Duration and time to hematologic response to ZN-d5 [48 months]
The rate of, duration of, and time to CR, modified Complete Response (mCR), CR+VGPR, and mCR+VGPR

Other Outcome Measures

To assess potential biomarker of ZN-d5 [48 months]
The number of peripheral B-Cells from blood tests

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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;
Adequate time since prior therapy before initiation of treatment (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);
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;

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Site 0198	Denver	Colorado	United States	80218
2	Site 0200	New Orleans	Louisiana	United States	70112
3	Site 2404	Saint Louis	Missouri	United States	63130
4	Site 0199	Nashville	Tennessee	United States	37203
5	Site 2711	Westmead	New South Wales	Australia	2145
6	Site 2712	Brisbane	Queensland	Australia	4102
7	Site 2714	Adelaide	South Australia	Australia	5000
8	Site 4101	Athens		Greece	115 28
9	Site 3804	Haifa		Israel	3109601
10	Site 3804	Haifa		Israel
11	Site 3805	Jerusalem		Israel
12	Site 3802	Ramat Gan		Israel
13	Site 3502	Barcelona	Badalona	Spain
14	Site 3507	El Palmar	Murcia	Spain	30120
15	Site 3509	Barcelona		Spain	08036
16	Site 3506	Salamanca		Spain