A Phase I Study of ZN-d5 in Chinese Subjects With Non-Hodgkin Lymphoma

A Phase I Dose Escalation Study of ZN-d5 Monotherapy in Chinese Subjects With Non-Hodgkin Lymphoma

A phase I dose-escalation, open-label, multicenter study to assess the safety, tolerability, clinical activity, and pharmacokinetics (PK) of ZN-d5 in Chinese subjects with non-Hodgkin lymphoma (NHL).

Study Overview

• Status: Terminated
• Conditions: Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: ZN-d5

Detailed Description

For the Phase I dose escalation study of ZN-d5, it is planned that after the starting dose, subsequent dose assignments will be made by means of a model-assisted design, until the MTD or RP2D is determined in the Chinese population.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Beijing
    • BeiJing, Beijing, China, 100142
      • Beijing Cancer Hospital
  • Guangdong
    • Guangzhou, Guangdong, China
      • Sun Yan Set University Cancer Center
  • Shanghai
    • Shanghai, Shanghai, China
      • Fudan University Shanghai Cancer Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. NHL, relapsed from or refractory to at least 2 prior lines of systemic therapy (excluding radiotherapy and surgery); subjects must have failed or not be candidates for available standard therapy expected to provide clinical benefit.
2. Female subjects of childbearing potential must have a negative serum pregnancy test and agree to use contraception while on study.
3. Eastern Cooperative Oncology Group performance status ≤ 1.

4. Adequate blood and other organ function, defined by the following criteria:

   1. Neutrophil count (ANC) ≥ 1.0 × 109/L.
   2. Platelet count ≥ 75 × 109/L at least 3 days after platelet transfusion (≥ 50 × 109/L permitted if the bone marrow is > 50% lymphoma cells).
   3. Hemoglobin ≥ 8.0 g/dL.
   4. Coagulation parameters ≤ 1.5 × upper limit of normal (ULN).
   5. Liver enzymes ≤ 3 × ULN and total bilirubin ≤ 1.5 × ULN.
   6. Creatinine clearance ≥ 60 mL/min.

Exclusion Criteria:

1. Received any of the following prior to start of ZN-d5 treatment:

   1. Systemic administration of antineoplastic agents (including investigational agents) within the shorter of 28 days or 5 half-lives.
   2. Major surgery within 28 days.
   3. Radiotherapy within 14 days.
   4. Autologous or allogeneic stem cell transplantation within 60 days, or receiving immunosuppression for active graft-versus-host disease.
   5. Use of strong CYP3A4 inhibitors, P-gp inhibitors or QT prolonging agents within 5 half-lives, or potent or moderate CYP3A4 inducers within 14 days.
2. Ongoing and clinically significant non-hematologic toxicity related to prior antineoplastic therapy.
3. Presence of major cardiovascular system diseases (including QTcF > 480 msec).
4. Positive serology for human immunodeficiency virus, hepatitis B, or hepatitis C unless no detectable hepatitis B or C viral load.
5. Unable to take oral drugs or presence of severe gastrointestinal abnormalities.
6. Active and uncontrolled clinically significant infection.
7. Other active systemic malignancy or other severe, unstable, or poorly controlled acute or chronic medical conditions.
8. Prior treatment with venetoclax or other BCL-2 inhibitors.
9. Primary or secondary CNS lymphoma.
10. Presence of post-transplant lymphoproliferative disease, Burkitt's lymphoma, Burkitt-like lymphoma, T lymphoblastic lymphoma and T lymphoblastic acute leukemia.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 100mg(on empty)	Drug: ZN-d5; BION design
Experimental: 200mg(on empty)	Drug: ZN-d5; BION design
Experimental: 400mg(on empty)	Drug: ZN-d5; BION design
Experimental: 600mg(on empty)	Drug: ZN-d5; BION design
Experimental: 600mg（with a meal）	Drug: ZN-d5; BION design
Experimental: 800mg(with a meal)	Drug: ZN-d5; BION design

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety monitoring	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	until 30 days after the last dose of study drug
DLT	Dose-limiting toxicities (DLTs) observed in DLT evaluable subjects	at the end of Cycle 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effacy Evaluation	Efficacy as defined by the 2014 Lugano response criteria	up to 24 months
Maximum Plasma Concentration [Cmax]	Plasma PK parameters of ZN-d5	up to 24 months

Collaborators and Investigators

• Sponsor: Zentera Therapeutics HK Limited

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2021
• Primary Completion (Actual): May 26, 2023
• Study Completion (Actual): May 26, 2023

Study Registration Dates

• First Submitted: September 18, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: d5ZTCN100

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes