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

NCT ID: NCT05065710

Last Updated: 2024-09-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-01-19
• Study Completion Date: 2024-04-09

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. The trial was intended to be a Phase 1/2 trial but the Phase 2 was not initiated.

Conditions

Advanced Solid Tumor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

ZL-1211 monotherapy

Group Type: EXPERIMENTAL

ZL-1211

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zai Biopharmaceutical (Suzhou) Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Zai Lab Site 2012

Scottsdale, Arizona, United States

Zai Lab Site 2016

Lynwood, California, United States

Zai Lab Site 2014

Indianapolis, Indiana, United States

Zai Site 2020

Hackensack, New Jersey, United States

Zai Lab Site 2025

New York, New York, United States

Zai Lab Site 2015

Cincinnati, Ohio, United States

Zai Lab Site 2011

Nashville, Tennessee, 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

Zai Lab Site 1725

Hefei, Anhui, China

Zai Lab Site 1548

Beijing, Beijing Municipality, China

Zai Lab Site 1551

Harbin, Heilongjiang, China

Zai Lab Site 1549

Zhengzhou, Henan, China

Zai Lab Site 1202

Zhengzhou, Henan, China

Zai Lab Site 1537

Wuhan, Hubei, China

Zai Lab Site 1539

Jinan, Shandong, China

Zai Lab Site 1542

Shanghai, Shanghai Municipality, China

Zai Lab Site 1712

Chengdu, Sichuan, China

Zai Lab Site 1529

Hangzhou, Zhejiang, China

Zai Lab Site 1714

Hangzhou, Zhejiang, China

Countries

United States; China

References

Konno H, Lin T, Wu R, Dai X, Li S, Wang G, Chen M, Li W, Wang L, Sun BC, Luo Z, Huang T, Chen Y, Zhang J, Ye Q, Bellovin D, Wan B, Kang L, Szeto C, Hsu K, Kabbarah O. ZL-1211 Exhibits Robust Antitumor Activity by Enhancing ADCC and Activating NK Cell-mediated Inflammation in CLDN18.2-High and -Low Expressing Gastric Cancer Models. Cancer Res Commun. 2022 Sep 7;2(9):937-950. doi: 10.1158/2767-9764.CRC-22-0216. eCollection 2022 Sep.

Reference Type: DERIVED

PMID: 36922936 (View on PubMed)

Other Identifiers

ZL-1211-001

Identifier Type: -

Identifier Source: org_study_id