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

NCT05065710 | Completed Phase 1 FDA Drug

• 1 other identifier: ZL-1211-001
• Study Type: interventional
• Target: 34
• Locations: 2 countries
• Sites: 21

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.

Conditions

Advanced Solid Tumor

Keywords

CLDN18.2; Solid tumor

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• Phase I and Phase II: pharmacokinetics (PK):AUC

  Approximately 10 months

• Phase I and Phase II: pharmacokinetics (PK):Cmax

  Approximately 10 months

• Phase I and Phase II: pharmacokinetics (PK):Tmax

  Approximately 10 months

• Phase I and Phase II: pharmacokinetics (PK):Ctrough

  Approximately 10 months

• Phase I and Phase II: pharmacokinetics (PK):Vss

  Approximately 10 months

Study Arms (1)

ZL-1211 monotherapy

EXPERIMENTAL

Drug: ZL-1211

Interventions

ZL-1211 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

ZL-1211 monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults≥ 18 years of age.
• 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.
• 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.
• Patients with histologically or cytologically confirmed metastatic or locally advanced solid tumors, refractory to standard treatment
• Evaluable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Adequate hepatic function
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; AST or ALT ≤ 5 × ULN if liver metastases are present.
• Adequate renal function, as defined by serum creatinine \< 1.5 × ULN OR calculated creatinine CL \> 40 mL/min, Cockroft-Gault Equation:
• Hematological function defined as:
• Absolute neutrophil count ≥ 1.5 × 109/L without growth factor support in the 2 weeks prior to screening.
• Platelet count ≥ 100 × 109/L without transfusion in the 2 weeks prior to screening.
• Hemoglobin ≥ 9 g/dL without transfusion in the 2 weeks prior to screening.
• Prothrombin time, international normalized ratio or/and activated partial thromboplastin time \< 1.5 × ULN.

You may not qualify if:

• 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.
• Any uncontrolled active infection.
• Previous exposure to any CLDN18.2 antibody or CLDN18.2 chimeric antigen receptor T cell therapy.
• Newly diagnosed or symptomatic brain metastases anticonvulsants are allowed.
• Severe cardiovascular disease; New York Heart Association Class II-IV heart failure within 6 months of screening; uncontrolled arrhythmia within 6 months of screening.
• 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.
• Major surgery within 4 weeks prior to first dose; minor surgery within 2 weeks prior to first dose.
• Symptomatic intrinsic lung disease (chronic obstructive pulmonary disease, pulmonary fibrosis).
• Gastrointestinal abnormalities including:
• Documented unresolved gastric outlet obstruction or persistent vomiting defined as ≥ 3 episodes within 24 hours.
• Active peptic ulcer disease required treatment in the past 3 months.
• Gastrointestinal bleeding as evidenced by hematemesis, hematochezia, or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy.
• Documented active colitis within 4 weeks prior to study entry, including infectious colitis, radiation colitis and ischemic colitis.
• History of ulcerative colitis or Crohn's disease.
• Patient has received systemic immunosuppressive therapy, including systemic corticosteroids 2 weeks prior to first dose of study drug.

Sponsors & Collaborators

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

Study Sites (21)

Zai Lab Site 2012

Scottsdale, Arizona, 85258, United States

Location

Zai Lab Site 2016

Lynwood, California, 90262, United States

Location

Zai Lab Site 2014

Indianapolis, Indiana, 46250, United States

Location

Zai Site 2020

Hackensack, New Jersey, 07601, United States

Location

Zai Lab Site 2025

New York, New York, 10016, United States

Location

Zai Lab Site 2015

Cincinnati, Ohio, 45219, United States

Location

Zai Lab Site 2011

Nashville, Tennessee, 37203, United States

Location

Zai Lab Site 2023

Fairfax, Virginia, 22031, United States

Location

Zai Lab Site 2013

Spokane, Washington, 99208, United States

Location

Zai Lab Site 2022

Tacoma, Washington, 98405, United States

Location

Zai Lab Site 1725

Hefei, Anhui, 230031, China

Location

Zai Lab Site 1548

Beijing, Beijing Municipality, 100032, China

Location

Zai Lab Site 1551

Harbin, Heilongjiang, 150000, China

Location

Zai Lab Site 1549

Zhengzhou, Henan, 450003, China

Location

Zai Lab Site 1202

Zhengzhou, Henan, 450052, China

Location

Zai Lab Site 1537

Wuhan, Hubei, 430022, China

Location

Zai Lab Site 1539

Jinan, Shandong, 250014, China

Location

Zai Lab Site 1542

Shanghai, Shanghai Municipality, 200092, China

Location

Zai Lab Site 1712

Chengdu, Sichuan, 610044, China

Location

Zai Lab Site 1529

Hangzhou, Zhejiang, 310003, China

Location

Zai Lab Site 1714

Hangzhou, Zhejiang, 310014, China

Location

Related Publications (1)

• 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.

  PMID: 36922936 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Phase I, the Dose Escalation Phase of the study will enroll patients with locally advanced or metastatic solid tumors of any histology with positive CLDN18.2. Phase II, the Cohort Expansion Phase of the study, will be conducted after determination of the dose level (RP2D) for cohort expansion based on the results of Phase I to explore the preliminary efficacy.

Study Record Dates

• First Submitted: September 12, 2021
• First Posted: October 4, 2021
• Study Start: January 19, 2022
• Primary Completion: March 9, 2024
• Study Completion: April 9, 2024
• Last Updated: September 3, 2024

Record last verified: 2024-08

Locations

US (10); CN (11)