<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04467853</url>
  </required_header>
  <id_info>
    <org_study_id>BM2L201910</org_study_id>
    <nct_id>NCT04467853</nct_id>
  </id_info>
  <brief_title>A Clinical Study to Evaluate CAR-T Cell-based Medicinal Product in the Treatment of Advanced Solid Tumors</brief_title>
  <official_title>A Phase 1, Open-Label Study Evaluating the Safety, Tolerability and Efficacy of LCAR-C18S, an CAR-T Cell Therapy Targeting Claudin18.2 in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai East Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Nanjing Legend Biotech Co.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Shanghai East Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to&#xD;
      evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the&#xD;
      cell-based LCAR-C18S (hereinafter &quot;LCAR-C18S&quot;) in subjects with Claudin18.2-positive advanced&#xD;
      solid Tumors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to&#xD;
      evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the&#xD;
      cell-based LCAR-C18S (hereinafter &quot;LCAR-C18S&quot;) in subjects with Claudin18.2-positive advanced&#xD;
      solid Tumors. Patients who meet the eligibility criteria will receive LCAR-C18S infusion. The&#xD;
      study will include the following sequential phases: screening, pre-treatment , treatment and&#xD;
      follow up&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Both the sponsors and collaborator are considering terminating the study&#xD;
  </why_stopped>
  <start_date type="Actual">September 21, 2020</start_date>
  <completion_date type="Actual">July 17, 2023</completion_date>
  <primary_completion_date type="Actual">July 17, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety</measure>
    <time_frame>Minimum 2 years after LCAR-C18S infusion (Day 1)</time_frame>
    <description>Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)</measure>
    <time_frame>90 days post infusion</time_frame>
    <description>To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Pharmacokinetic (PK) parameters</measure>
    <time_frame>Minimum 2 years after LCAR-C18S infusion (Day 1)</time_frame>
    <description>Blood samples will be collected for determination of cellular concentrations and transgenic levels of serum LCAR-C18S for pharmacokinetic analysis</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall response rate (ORR) after administration</measure>
    <time_frame>Minimum 2 years after LCAR-C18S infusion (Day 1)</time_frame>
    <description>Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-C18S cell infusion, and the objective tumor response rate will be calculated for patients with measurable disease per RECIST 1.1 only</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progress Free Survival (PFS) after administration</measure>
    <time_frame>Minimum 2 years after LCAR-C18S infusion (Day 1)</time_frame>
    <description>Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-C18S to the first documented disease progression (according to RECIST 1.1) or death (due to any cause), whichever occurs first</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) after administration</measure>
    <time_frame>Minimum 2 years after LCAR-C18S infusion (Day 1)</time_frame>
    <description>Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-C18S to death of the subject.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Solid Tumors, Adult</condition>
  <arm_group>
    <arm_group_label>LCAR-C18S Cells</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive LCAR-C18S Cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>LCAR-C18S cells</intervention_name>
    <description>Before treatment with LCAR-C18S cells, subjects will receive a conditioning regimen</description>
    <arm_group_label>LCAR-C18S Cells</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. The subjects have been fully informed of the possible risks and benefits of&#xD;
             participating in the study and have signed the informed consent form;&#xD;
&#xD;
          2. Age 18-70 years;&#xD;
&#xD;
          3. Immunohistochemistry of tumor tissue samples indicates Claudin18.2 positive ;&#xD;
&#xD;
          4. Recurrent or metastatic advanced solid tumors (including advanced gastric cancers and&#xD;
             non-gastric cancers) and have been failed to prior lines of systemic treatment&#xD;
&#xD;
          5. According to the RECIST v1.1, at least one measuable tumor lesion;&#xD;
&#xD;
          6. ECOG performance status score of 0-1;&#xD;
&#xD;
          7. Expected survival ≥ 3 months;&#xD;
&#xD;
          8. Subjects should have adequate organ functions before screening and treatment.&#xD;
&#xD;
          9. Women of childbearing age must have a negative blood pregnancy test; subjects of&#xD;
             childbearing potential must use effective contraception for ≥ 1 year after the final&#xD;
             study treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous CAR-T cell therapy or other cell therapies or therapeutic tumor vaccination&#xD;
             against any target;&#xD;
&#xD;
          2. Any previous therapy targeting Claudin18.2;&#xD;
&#xD;
          3. Prior antitumor therapy with insufficient washout period;&#xD;
&#xD;
          4. Pregnant or lactating women;&#xD;
&#xD;
          5. Brain metastases with central nervous system symptoms;&#xD;
&#xD;
          6. Uncontrolled diabetes;&#xD;
&#xD;
          7. Oxygen is required to maintain adequate blood oxygen saturation;&#xD;
&#xD;
          8. Gastric perforation, pyloric obstruction, complete biliary obstruction, complete or&#xD;
             incomplete intestinal obstruction requiring clinical intervention, or pleural effusion&#xD;
             or peritoneal effusion requiring clinical intervention;&#xD;
&#xD;
          9. Clinically significant liver disorders (including liver cirrhosis, active viral&#xD;
             hepatitis or other hepatitis);&#xD;
&#xD;
         10. HIV, Treponema pallidum or HCV serologically positive;&#xD;
&#xD;
         11. Severe underlying disease&#xD;
&#xD;
         12. New York Heart Association (NYHA) Class III or IV congestive heart failure or left&#xD;
             ventricular ejection fraction (LVEF) &lt; 50%; unstable angina, myocardial infarction or&#xD;
             coronary artery bypass grafting (CABG) in the past 6 months; history of severe&#xD;
             non-ischemic cardiomyopathy; or severe uncontrolled arrhythmia;&#xD;
&#xD;
         13. Any condition that, in the opinion of the investigator, will make the subject&#xD;
             unsuitable for participation in this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jin Li, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai East Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Anhui Provincial Hospital</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>China/Shanghai</state>
        <zip>200126</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shanghai Artemed Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>July 1, 2020</study_first_submitted>
  <study_first_submitted_qc>July 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>August 11, 2023</last_update_submitted>
  <last_update_submitted_qc>August 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 15, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai East Hospital</investigator_affiliation>
    <investigator_full_name>Jin Li</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04467853
org study id: BM2L201910
nct id: NCT04467853
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to
      evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the
      cell-based LCAR-C18S (hereinafter "LCAR-C18S") in subjects with Claudin18.2-positive advanced
      solid Tumors.
This is a prospective, single-arm, open-label Phase 1 dose-finding and expansion study to
      evaluate the safety, tolerability, pharmacokinetics, and anti-tumor efficacy profiles of the
      cell-based LCAR-C18S (hereinafter "LCAR-C18S") in subjects with Claudin18.2-positive advanced
      solid Tumors. Patients who meet the eligibility criteria will receive LCAR-C18S infusion. The
      study will include the following sequential phases: screening, pre-treatment , treatment and
      follow up
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
time frame: Minimum 2 years after LCAR-C18S infusion (Day 1)
description: Dose-limiting toxicity (DLT) and incidence, severity, and type of treatment-emergent adverse events (TEAEs),Safety
measure: To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
time frame: 90 days post infusion
description: To determine the recommended dose of the phase Ⅱ trial of this cell therapy (RP2D)
measure: Pharmacokinetic (PK) parameters
time frame: Minimum 2 years after LCAR-C18S infusion (Day 1)
description: Blood samples will be collected for determination of cellular concentrations and transgenic levels of serum LCAR-C18S for pharmacokinetic analysis
measure: Overall response rate (ORR) after administration
time frame: Minimum 2 years after LCAR-C18S infusion (Day 1)
description: Objective Response Rate (ORR) is defined as the proportion of subjects who achieve CR or PR after treatment via LCAR-C18S cell infusion, and the objective tumor response rate will be calculated for patients with measurable disease per RECIST 1.1 only
measure: Progress Free Survival (PFS) after administration
time frame: Minimum 2 years after LCAR-C18S infusion (Day 1)
description: Progression Free Survival (PFS) is defined as the time from the date of first infusion of the LCAR-C18S to the first documented disease progression (according to RECIST 1.1) or death (due to any cause), whichever occurs first
measure: Overall Survival (OS) after administration
time frame: Minimum 2 years after LCAR-C18S infusion (Day 1)
description: Overall Survival (OS) is defined as the time from the date of first infusion of LCAR-C18S to death of the subject.
arm group label: LCAR-C18S Cells
arm group type: Experimental
description: Each subject will receive LCAR-C18S Cells
intervention type: Biological
intervention name: LCAR-C18S cells
description: Before treatment with LCAR-C18S cells, subjects will receive a conditioning regimen
arm group label: LCAR-C18S Cells
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jin Li, MD, PhD
role: Principal Investigator
affiliation: Shanghai East Hospital
facility: 
facility: 
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai East Hospital
investigator full name: Jin Li
investigator title: Director
mesh term: Neoplasms
sharing ipd: No