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

Phase 1

Active, not recruiting

• Conditions: AL Amyloidosis; Amyloidosis
• Interventions: Drug: ZN-d5

• Registration Number: NCT05199337
• Lead Sponsor: K-Group Alpha, Inc., a wholly owned subsidiary of Zentalis Pharmaceuticals, Inc.

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.

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 Timeline

• Study Start: 2021-11-30
• Study First Submitted: 2022-01-09
• Study First Submitted QC: 2022-01-18
• Study First Posted: 2022-01-20
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-04
• Last Update Posted: 2024-03-05
• Primary Completion: 2025-05
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 135

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment Arm	ZN-d5	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.

Primary Outcome Measures

Name	Time	Method
Dose limiting toxicities	18 Months	Incidence of Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects
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

Secondary Outcome Measures

Name	Time	Method
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 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.
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
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
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.

Trial Locations

Locations (21)

University of Southern California; 🇺🇸 Los Angeles, California, United States

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

Tennessee Oncology; 🇺🇸 Nashville, Tennessee, United States

Bank of Cyprus Hospital; 🇨🇾 Nicosia, Cyprus

Hadassah Medical Center; 🇮🇱 Jerusalem, Israel

National and Kapodistrian University of Athens; 🇬🇷 Athens, Greece

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States

Tulane University; 🇺🇸 New Orleans, Louisiana, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Blackwater (Westmead) Hospital; 🇦🇺 Westmead, New South Wales, Australia

Sir Charles Gairdner Hospital; 🇦🇺 Nedlands, Western Australia, Australia

Sheba Medical Center; 🇮🇱 Tel Aviv, Israel

IRCCS Azienda Ospedaliero Universitaria di Bologna Policlinico Sant'Orsola Malpighi; 🇮🇹 Bologna, Italy

Rambam Hospital; 🇮🇱 Haifa, Israel

Tel Aviv Sourasky Medical Center PPDS; 🇮🇱 Tel Aviv, Israel

Fondazione I.R.C.C.S. Policlinico San Matteo; 🇮🇹 Pavia, Italy

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, Spain

Hospital Clinic de Barcelona; 🇪🇸 Barcelona, Spain

Princess Alexandra Hospital; 🇦🇺 Brisbane, Queensland, Australia