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

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ClinicalTrials.gov Identifier: NCT05065710
Recruitment Status : Recruiting
First Posted : October 4, 2021
Last Update Posted : October 4, 2021
Sponsor:
Information provided by (Responsible Party):
Zai Lab (Hong Kong), Ltd. ( 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.

Condition or disease Intervention/treatment Phase
Advanced Solid Tumor Drug: ZL-1211 Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 162 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 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.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase I/II, First-in-Human, Open-Label, Dose Escalation Study of ZL- 1211 in Patients With Unresectable or Metastatic Solid Tumor
Estimated Study Start Date : September 30, 2021
Estimated Primary Completion Date : November 30, 2023
Estimated Study Completion Date : July 30, 2024

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




Primary Outcome Measures :
  1. Phase I :MTD or MAD [ Time Frame: One month ]
    To determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) (if no MTD is defined) of ZL-1211

  2. Phase I and Phase II: safety and tolerability [ Time Frame: Approximately 10 months ]
    Incidence of Treatment-Related Adverse Events as Assessed by CTCAE v5.0

  3. Phase II: preliminary antitumor activity [ Time Frame: 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 :
  1. Phase I and Phase II: pharmacokinetics (PK):AUC [ Time Frame: Approximately 10 months ]
    Area under the curve (AUC)

  2. Phase I and Phase II: pharmacokinetics (PK):Cmax [ Time Frame: Approximately 10 months ]
    Maximum serum concentration (Cmax)

  3. Phase I and Phase II: pharmacokinetics (PK):Tmax [ Time Frame: Approximately 10 months ]
    Time to reach Cmax (Tmax)

  4. Phase I and Phase II: pharmacokinetics (PK):Ctrough [ Time Frame: Approximately 10 months ]
    Ctrough

  5. Phase I and Phase II: pharmacokinetics (PK):Vss [ Time Frame: Approximately 10 months ]
    Volume of distribution at steady state (Vss)

  6. Phase I and Phase II: pharmacokinetics (PK):CL [ Time Frame: Approximately 10 months ]
    Clearance (CL)

  7. Phase I and Phase II: pharmacokinetics (PK):t1/2 [ Time Frame: Approximately 10 months ]
    Half-life (t1/2)

  8. Phase I and Phase II: immunogenicity [ Time Frame: Approximately 10 months ]
    Incidence of anti-drug antibodies (ADAs)

  9. Phase I and Phase II: immunogenicity [ Time Frame: Approximately 10 months ]
    Quantity of anti-drug antibodies (ADAs)

  10. Phase II: preliminary antitumor activity [ Time Frame: 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



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05065710


Contacts
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Contact: Zai Biopharmaceutical (Suzhou) Co., Ltd. +862161632588 Study-ZL-1211-001@zailaboratory.com

Locations
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United States, Arizona
2012 Not yet recruiting
Scottsdale, Arizona, United States, 85258
Contact: Sunil Sharma         
United States, Indiana
2014 Not yet recruiting
Indianapolis, Indiana, United States, 46250
Contact: Bert O'Neil         
United States, Tennessee
2011 Recruiting
Nashville, Tennessee, United States, 37203
Contact: David Spigel         
United States, Washington
2013 Not yet recruiting
Spokane, Washington, United States, 99208
Contact: Arvind Chaudhry         
Sponsors and Collaborators
Zai Biopharmaceutical (Suzhou) Co., Ltd.
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Responsible Party: Zai Biopharmaceutical (Suzhou) Co., Ltd.
ClinicalTrials.gov Identifier: NCT05065710    
Other Study ID Numbers: ZL-1211-001
First Posted: October 4, 2021    Key Record Dates
Last Update Posted: October 4, 2021
Last Verified: September 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Zai Lab (Hong Kong), Ltd. ( Zai Biopharmaceutical (Suzhou) Co., Ltd. ):
CLDN18.2
Solid tumor
Additional relevant MeSH terms:
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Neoplasms