A Study of ZL-1211 in Patients With Advanced Solid Tumor

A Phase I, First-in-Human, Open-Label, Dose Escalation Study of ZL- 1211 in Patients With Unresectable or Metastatic Solid Tumor

This study is a Phase I/II, open-label, dose escalation, and cohort expansion study designed to characterize the safety, tolerability, pharmacokinetic (PK), pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of ZL-1211 administered by IV infusion on a every 2 weeks (Q2W) schedule.

Study Overview

• Status: Completed
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Drug: ZL-1211

Detailed Description

The study consists of two stages, Phase I -Dose Escalation Phase to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211, and Phase II -Cohort Expansion Phase to further define the safety and initial antitumor activity of ZL-1211 with the dose established in the Dose Escalation Phase. The trial was intended to be a Phase 1/2 trial but the Phase 2 was not initiated.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230031
      • Zai Lab Site 1725
  • Beijing
    • Beijing, Beijing, China, 100032
      • Zai Lab Site 1548
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Zai Lab Site 1551
  • Henan
    • Zhengzhou, Henan, China, 450003
      • Zai Lab Site 1549
    • Zhengzhou, Henan, China, 450052
      • Zai Lab Site 1202
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Zai Lab Site 1537
  • Shandong
    • Jinan, Shandong, China, 250014
      • Zai Lab Site 1539
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Zai Lab Site 1542
  • Sichuan
    • Chengdu, Sichuan, China, 610044
      • Zai Lab Site 1712
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • Zai Lab Site 1529
    • Hangzhou, Zhejiang, China, 310014
      • Zai Lab Site 1714
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • Zai Lab Site 2012
  • California
    • Lynwood, California, United States, 90262
      • Zai Lab Site 2016
  • Indiana
    • Indianapolis, Indiana, United States, 46250
      • Zai Lab Site 2014
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Zai Site 2020
  • New York
    • New York, New York, United States, 10016
      • Zai Lab Site 2025
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Zai Lab Site 2015
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Zai Lab Site 2011
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Zai Lab Site 2023
  • Washington
    • Spokane, Washington, United States, 99208
      • Zai Lab Site 2013
    • Tacoma, Washington, United States, 98405
      • Zai Lab Site 2022

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Patients are eligible to be included in the study only if all the following inclusion criteria apply:

1. Adults≥ 18 years of age.
2. Willing and able to provide signed and dated informed consent prior to any study related procedures and willing and able to comply with all study procedures.
3. All patients from Phase I and Phase II are required to provide tumor tissue for CLDN18.2 IHC assessment, and only patients with CLDN18.2-positive tumors will be included in this study.
4. Patients with histologically or cytologically confirmed metastatic or locally advanced solid tumors, refractory to standard treatment
5. Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
6. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.

7. Adequate hepatic function

   1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
   2. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present.
8. Adequate renal function, as defined by serum creatinine < 1.5 × ULN OR calculated creatinine CL > 40 mL/min, Cockroft-Gault Equation:

9. Hematological function defined as:

   1. Absolute neutrophil count ≥ 1.5 × 109/L without growth factor support in the 2 weeks prior to screening.
   2. Platelet count ≥ 100 × 109/L without transfusion in the 2 weeks prior to screening.
   3. Hemoglobin ≥ 9 g/dL without transfusion in the 2 weeks prior to screening.
10. Prothrombin time, international normalized ratio or/and activated partial thromboplastin time < 1.5 × ULN.
11. Recovery, to Grade 0-1, from AEs related to prior anticancer therapy except alopecia, < Grade 2 sensory neuropathy, lymphopenia.

Exclusion Criteria:

1. Patient with known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome related illness or known active or chronic hepatitis B virus infection or hepatitis C virus.
2. Any uncontrolled active infection.
3. Previous exposure to any CLDN18.2 antibody or CLDN18.2 chimeric antigen receptor T cell therapy.
4. Newly diagnosed or symptomatic brain metastases anticonvulsants are allowed.
5. Severe cardiovascular disease; New York Heart Association Class II-IV heart failure within 6 months of screening; uncontrolled arrhythmia within 6 months of screening.
6. Anticancer therapy or radiation therapy within 5 half-lives or 4 weeks (whichever is shorter) prior to screening; palliative radiotherapy within 2 weeks prior to screening.
7. Major surgery within 4 weeks prior to first dose; minor surgery within 2 weeks prior to first dose.
8. Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis).

9. Gastrointestinal abnormalities including:

   1. Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥ 3 episodes within 24 hours.
   2. Active peptic ulcer disease required treatment in the past 3 months.
   3. Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
   4. Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis.
   5. History of ulcerative colitis or Crohn's disease.
10. Patient has received systemic immunosuppressive therapy, including systemic corticosteroids 2 weeks prior to first dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ZL-1211 monotherapy	Drug: ZL-1211; Phase 1 dose escalation part will enroll about 12-42 patients, Phase 2 dose expansion part will enroll about 15-40 patients in each cohort

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I ：MTD or MAD	To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211	One month
Phase I and Phase II: safety and tolerability	Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0	Approximately 10 months
Phase II: preliminary antitumor activity	Objective response rate defined as the proportion of patients with partial response (PR) proportion of patients with partial response (PR) or complete response (CR) based on Investigator assessment of tumor lesions per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Approximately 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase I and Phase II: pharmacokinetics (PK):AUC	Area under the curve (AUC)	Approximately 10 months
Phase I and Phase II: pharmacokinetics (PK):Cmax	Maximum serum concentration (Cmax)	Approximately 10 months
Phase I and Phase II: pharmacokinetics (PK):Tmax	Time to reach Cmax (Tmax)	Approximately 10 months
Phase I and Phase II: pharmacokinetics (PK):Ctrough	Ctrough	Approximately 10 months
Phase I and Phase II: pharmacokinetics (PK):Vss	Volume of distribution at steady state (Vss)	Approximately 10 months
Phase I and Phase II: pharmacokinetics (PK):CL	Clearance (CL)	Approximately 10 months
Phase I and Phase II: pharmacokinetics (PK):t1/2	Half-life (t1/2)	Approximately 10 months
Phase I and Phase II: immunogenicity	Incidence of anti-drug antibodies (ADAs)	Approximately 10 months
Phase I and Phase II: immunogenicity	Quantity of anti-drug antibodies (ADAs)	Approximately 10 months
Phase II: preliminary antitumor activity	Duration of response (DOR), defined as the time from the first date of objective response (CR or PR) to the first documented date of disease progression per RECIST v1.1 or the date of death due to any cause, whichever occurs first	Approximately 10 months

Collaborators and Investigators

• Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2022
• Primary Completion (Actual): March 9, 2024
• Study Completion (Actual): April 9, 2024

Study Registration Dates

• First Submitted: September 12, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 28, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Solid tumor; CLDN18.2
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: ZL-1211-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No