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

• Status: Recruiting
• Trial end date: 2025-12-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: K-Group Alpha, Inc.

Criteria

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. Measurable disease defined by serum differential free light chain;

4. Bone marrow plasma cells <30%;

5. Assessment of t(11,14) status by FISH;

6. Eastern Cooperative Oncology Group performance <2 ;

7. History of organ involvement (current measurable organ disease is not required for enrollment): Renal, Cardiac, Hepatic, Gastrointestinal, and Neurologic;

8. Adequate bone marrow function prior to first administration of study drug;

9. Adequate organ function;

• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x ULN;

• Alkaline phosphatase ≤5 x ULN;

• Total bilirubin ≤1.5 x ULN except for subjects with Gilbert syndrome;

• Estimated glomerular filtration rate (CKD-EPI) ≥45 mL/min/1.73 m2;

10. Female subjects of childbearing potential must have a negative serum pregnancy test and agree to use contraception while on study.

Exclusion Criteria:

1. Presence of non-AL amyloidosis, including wild type or mutated ATTR amyloidosis.;

2. Diagnosis of multiple myeloma;

3. Mayo2012 Stage IV disease: NT-ProBNP ≥ 1800 ng/L, cTnT ≥ 0.025 ng/mL (0.025 µg/L), and dFLC ≥ 180 mg/L;

4. Cardiac conditions including:

• New York Heart Association (NYHA) Class III or IV heart failure;

• History of sustained ventricular tachycardia or fibrillation, or ventricular arrhythmias

• QTc >500 msec;

• Atrial fibrillation with inadequate anti-coagulation;

• Second- or third-degree atrioventricular block (Mobitz type I is permitted);

• History of myocardial infarction, coronary stent placement, or coronary artery bypass grafting;

• Left ventricular ejection fraction (LVEF) by echocardiogram <35%;

• Supine systolic blood pressure <90 mm Hg or symptomatic orthostatic hypotension (decrease in systolic blood pressure upon standing of >20 mm Hg;

5. Positive serology for human immunodeficiency virus, hepatitis B, or hepatitis C unless no detectable hepatitis C viral load;

6. Concurrent treatment with drugs that prolong the QT interval, are strong CYP3A inhibitors or strong or moderate CYP3A inducers, or are P-glycoprotein inhibitors;

7. Concurrent treatment with agents used to treat plasma cell disorders or AL amyloidosis, including experimental agents;

8. Prior treatment with venetoclax or other BCL-2 inhibitors;

9. Other active systemic malignancy or other severe, unstable, or poorly controlled acute, chronic medical conditions or active and uncontrolled clinically significant infection;

10. Females who are pregnant or intending to become pregnant, or who are breastfeeding or intending to breastfeed, during the study.