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

Phase 1

Completed

• Conditions: Advanced Solid Tumor
• Interventions: Drug: ZL-1211

• Registration Number: NCT05065710
• Lead Sponsor: Zai Biopharmaceutical (Suzhou) Co., Ltd.

Brief Summary

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.

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.

Study Timeline

• Study First Submitted: 2021-09-12
• Study First Submitted QC: 2021-09-22
• Study First Posted: 2021-10-04
• Study Start: 2022-01-19
• Primary Completion: 2024-03-09
• Study Completion: 2024-04-09
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-22
• Last Update Posted: 2024-05-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ZL-1211 monotherapy	ZL-1211	-

Primary Outcome Measures

Name	Time	Method
Phase I ：MTD or MAD	One month	To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211
Phase I and Phase II: safety and tolerability	Approximately 10 months	Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Phase II: preliminary antitumor activity	Approximately 10 months	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

Secondary Outcome Measures

Name	Time	Method
Phase I and Phase II: pharmacokinetics (PK):Cmax	Approximately 10 months	Maximum serum concentration (Cmax)
Phase I and Phase II: pharmacokinetics (PK):AUC	Approximately 10 months	Area under the curve (AUC)
Phase I and Phase II: pharmacokinetics (PK):t1/2	Approximately 10 months	Half-life (t1/2)
Phase I and Phase II: pharmacokinetics (PK):Ctrough	Approximately 10 months	Ctrough
Phase I and Phase II: pharmacokinetics (PK):Tmax	Approximately 10 months	Time to reach Cmax (Tmax)
Phase I and Phase II: pharmacokinetics (PK):CL	Approximately 10 months	Clearance (CL)
Phase I and Phase II: immunogenicity	Approximately 10 months	Quantity of anti-drug antibodies (ADAs)
Phase II: preliminary antitumor activity	Approximately 10 months	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
Phase I and Phase II: pharmacokinetics (PK):Vss	Approximately 10 months	Volume of distribution at steady state (Vss)

Trial Locations

Locations (21)

Zai Site 2020; 🇺🇸 Hackensack, New Jersey, United States

Zai Lab Site 2025; 🇺🇸 New York, New York, United States

Zai Lab Site 1542; 🇨🇳 Shanghai, Shanghai, China

Zai Lab Site 2011; 🇺🇸 Nashville, Tennessee, United States

Zai Lab Site 1551; 🇨🇳 Harbin, Heilongjiang, China

Zai Lab Site 1548; 🇨🇳 Beijing, Beijing, China

Zai Lab Site 1529; 🇨🇳 Hangzhou, Zhejiang, China

Zai Lab Site 1549; 🇨🇳 Zhengzhou, Henan, China

Zai Lab Site 2012; 🇺🇸 Scottsdale, Arizona, United States

Zai Lab Site 1712; 🇨🇳 Chengdu, Sichuan, China

Zai Lab Site 1202; 🇨🇳 Zhengzhou, Henan, China

Zai Lab Site 1539; 🇨🇳 Jinan, Shandong, China

Zai Lab Site 1537; 🇨🇳 Wuhan, Hubei, China

Zai Lab Site 2014; 🇺🇸 Indianapolis, Indiana, United States

Zai Lab Site 2016; 🇺🇸 Lynwood, California, United States

Zai Lab Site 1725; 🇨🇳 Hefei, Anhui, China

Zai Lab Site 1714; 🇨🇳 Hangzhou, Zhejiang, China

Zai Lab Site 2015; 🇺🇸 Cincinnati, Ohio, United States

Zai Lab Site 2023; 🇺🇸 Fairfax, Virginia, United States

Zai Lab Site 2013; 🇺🇸 Spokane, Washington, United States

Zai Lab Site 2022; 🇺🇸 Tacoma, Washington, United States