xml: <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/NCT05981235</url>
    </required_header>
    <id_info>
      <org_study_id>D9540C00001</org_study_id>
      <nct_id>NCT05981235</nct_id>
    </id_info>
    <brief_title>Phase 1 Trial of AZD6422 in CLDN18.2+ GI Tumors</brief_title>
    <official_title>FTiH, Phase 1 Investigator-Initiated Trial (IIT) to Evaluate the Safety, Feasibility, Cellular Kinetics, and Preliminary Antitumor Activity of AZD6422 in Adult Participants With Advanced or Metastatic CLDN18.2+ GI Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>AstraZeneca</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Peking University</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 FTiH, Phase 1 IIT to evaluate the safety, feasibility, cellular kinetics (CK),&#xD;
        pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of AZD6422 in adult&#xD;
        participants with advanced or metastatic CLDN18.2+ GI tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Qualified researchers can request access to anonymized individual patient-level data from&#xD;
        sponsor or the collaborator group of companies sponsored clinical trials via the request&#xD;
        portal. All requests will be evaluated as per the sponsor disclosure commitment. Yes,&#xD;
        indicates that sponsors are accepting requests for IPD, but this does not mean all requests&#xD;
        will be shared.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 23, 2023</start_date>
    <completion_date type="Anticipated">November 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2026</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>Incidence of treatment-emergent AEs, AESIs, and SAEs.</measure>
      <time_frame>Within 24 months of the last AZD6422 infusion or the start of a new anticancer treatment</time_frame>
      <description>Incidence of treatment-emergent AEs, AESIs, and SAEs.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Occurrence of Dose limiting toxicity.</measure>
      <time_frame>Within 28 days after the first infusion</time_frame>
      <description>Occurrence of DLTs (Dose limiting toxicity).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Changes from baseline in vital signs, laboratory parameters, physical examination, and 12-lead ECG.</measure>
      <time_frame>Within 28 days after the first infusion</time_frame>
      <description>Changes from baseline in vital signs, laboratory parameters, physical examination, and 12-lead ECG.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ORR</measure>
      <time_frame>24 months post AZD6422 infusion</time_frame>
      <description>The proportion of participants who have a confirmed CR or confirmed PR as determined by the investigator at local site per RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DoR</measure>
      <time_frame>24 months post AZD6422 infusion</time_frame>
      <description>The time from first documented confirmed response until date of documented progression of disease per RECIST v1.1 as determined by investigator at local site or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>24 months post AZD6422 infusion</time_frame>
      <description>The proportion of participants who have a confirmed CR, confirmed PR, or who have SD per RECIST v1.1 as assessed by the investigator at local site and derived from the raw tumor data for at least 11 weeks after infusion date.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>24 months post AZD6422 infusion</time_frame>
      <description>Time from infusion date until progression per RECIST v1.1 as assessed by the investigator at local site, or death due to any cause.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">96</enrollment>
    <condition>Gastrointestinal Tumors</condition>
    <arm_group>
      <arm_group_label>AZD6422</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>It is anti-CLDN18.2 CAR-T cell therapy and the study consists of two parts: dose escalation (part 1) and dose expansion (part 2)</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>AZD6422 CLDN18.2 CAR-T product</intervention_name>
      <description>AZD6422 CAR-T product infusion after pre-conditioning</description>
      <arm_group_label>AZD6422</arm_group_label>
      <other_name>AZD6422</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  1Capable of giving signed informed consent and keep compliance with the requirements&#xD;
               and restrictions listed in the ICF and in this protocol.&#xD;
  &#xD;
               2Age ≥ 18 years at the time of signing the informed consent. 3At least 1 lesion, that&#xD;
               qualifies as a RECIST v1.1 target lesion at baseline. Histologically confirmed&#xD;
               diagnosis of unresectable or metastatic GI adenocarcinoma that has failed prior lines&#xD;
               systemic treatment or with standard anticancer therapy.&#xD;
  &#xD;
               4Confirmation of CLDN18.2 expression determined by IHC . 5ECOG PS of 0 to 1. 6 Life&#xD;
               expectancy of &gt; 12 weeks. 7Evidence of appropriate organ function, as determined by&#xD;
               clinical laboratory values.&#xD;
  &#xD;
               8Participants of childbearing potential (including woman of childbearing potential and&#xD;
               males who have a partner) must take highly effective contraception measure.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  1.Prior treatment with any CAR-T cell therapy. 2.History of upper digestive tract&#xD;
               bleeding secondary to previous CLDN18.2-targeting therapies; clinically significant&#xD;
               unstable or active peptic ulcer disease or upper digestive tract bleeding&#xD;
               3.Cancer-related spinal cord compression, leptomeningeal disease, or brain metastases.&#xD;
  &#xD;
               4.Receipt of the last dose of anticancer therapy within 5 half-lives or ≤ 21 days&#xD;
               prior to apheresis, treatment radiotherapy within 6 weeks (loco-regional palliative&#xD;
               radiotherapy within 7 days) prior to apheresis.&#xD;
  &#xD;
               5.Treatment with any anticoagulant or antiplatelet therapy. 6.History of, or active,&#xD;
               bleeding diatheses. 7.Active or chronic infection disease (s). 8.History of another&#xD;
               primary malignancy ≤ 3 years before enrolment. 9.Any history of autoimmune&#xD;
               neurological conditions. 10.Other active autoimmune or inflammatory disorders.&#xD;
               11.Stroke, intracranial haemorrhage, or seizure within 6 months of apheresis.&#xD;
               12.Active uncontrolled epilepsy. 13.Cardiac disease, including arrhythmias, QT&#xD;
               prolongation, cardiomyopathy and unstable ischaemic heart disease.&#xD;
  &#xD;
               14.Uncontrolled intercurrent illness. 15.Steroids or other immunomodulators of&#xD;
               systemic therapeutic dose within 14 days prior to apheresis.&#xD;
  &#xD;
               16.Prior pegylated G-CSF within 60 days before apheresis. Prior&#xD;
               G-CSF/granulocyte-macrophage colony stimulating factor (GM-CSF) within 14 days before&#xD;
               apheresis.&#xD;
  &#xD;
               17.Any prohibited medication. 18.Major surgery within 2 weeks prior to apheresis, or&#xD;
               planned surgery within 4 weeks after study intervention.&#xD;
  &#xD;
               19.Any history of life-threatening allergies, hypersensitivity, or severe infusion&#xD;
               reaction to monoclonal antibodies or biological therapies, or intolerance to the CAR-T&#xD;
               product or its excipients.&#xD;
  &#xD;
               20.Toxicity from previous anticancer therapy that has not resolved to baseline levels&#xD;
               or to ≤ Grade 1 prior to apheresis.&#xD;
  &#xD;
               21.Female participants who are pregnant or breastfeeding or expect to be pregnant or&#xD;
               breastfeeding during the study.&#xD;
  &#xD;
               22.Judgment by the investigator that the participant should not participate in the&#xD;
               study if the participant is unlikely to comply with study procedures, restrictions,&#xD;
               and requirements.&#xD;
  &#xD;
               23.Receipt of live or live attenuated vaccine within 30 days prior to the start of&#xD;
               lymphodepletion.&#xD;
  &#xD;
               24.Participant has any medical or psychiatric condition.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Lin Shen, PHD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Lin Shen, PHD</last_name>
      <phone>01088196090</phone>
      <email>linshenpku@163.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Beijing Cancer Hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Lin Shen, PHD</last_name>
      </contact>
      <investigator>
        <last_name>Lin Shen, PHD</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>August 1, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>CLDN18.2+ GI Tumors Solid tumor CAR-T Cell therapy AZD6422</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Digestive System Neoplasms</mesh_term>
      <mesh_term>Gastrointestinal Neoplasms</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Qualified researchers can request access to anonymized individual patient-level data from sponsor or the collaborator group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the sponsor disclosure commitment. Yes, indicates that sponsors are accepting requests for IPD, but this does not mean all requests will be shared.</ipd_description>
      <ipd_time_frame>Sponsor or the collaborator group of companies will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to disclosure commitment.</ipd_time_frame>
      <ipd_access_criteria>When a request has been approved sponsor will provide access to the de-identified individual patient-level detain an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.</ipd_access_criteria>
      <ipd_url>https://vivli.org/</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05981235
  org study id: D9540C00001
  nct id: NCT05981235
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a FTiH, Phase 1 IIT to evaluate the safety, feasibility, cellular kinetics (CK),
        pharmacodynamics (PD), immunogenicity, and preliminary antitumor activity of AZD6422 in adult
        participants with advanced or metastatic CLDN18.2+ GI tumors.
  Qualified researchers can request access to anonymized individual patient-level data from
        sponsor or the collaborator group of companies sponsored clinical trials via the request
        portal. All requests will be evaluated as per the sponsor disclosure commitment. Yes,
        indicates that sponsors are accepting requests for IPD, but this does not mean all requests
        will be shared.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of treatment-emergent AEs, AESIs, and SAEs.
  time frame: Within 24 months of the last AZD6422 infusion or the start of a new anticancer treatment
  description: Incidence of treatment-emergent AEs, AESIs, and SAEs.
  measure: Occurrence of Dose limiting toxicity.
  time frame: Within 28 days after the first infusion
  description: Occurrence of DLTs (Dose limiting toxicity).
  measure: Changes from baseline in vital signs, laboratory parameters, physical examination, and 12-lead ECG.
  time frame: Within 28 days after the first infusion
  description: Changes from baseline in vital signs, laboratory parameters, physical examination, and 12-lead ECG.
  measure: ORR
  time frame: 24 months post AZD6422 infusion
  description: The proportion of participants who have a confirmed CR or confirmed PR as determined by the investigator at local site per RECIST v1.1.
  measure: DoR
  time frame: 24 months post AZD6422 infusion
  description: The time from first documented confirmed response until date of documented progression of disease per RECIST v1.1 as determined by investigator at local site or death due to any cause.
  measure: DCR
  time frame: 24 months post AZD6422 infusion
  description: The proportion of participants who have a confirmed CR, confirmed PR, or who have SD per RECIST v1.1 as assessed by the investigator at local site and derived from the raw tumor data for at least 11 weeks after infusion date.
  measure: PFS
  time frame: 24 months post AZD6422 infusion
  description: Time from infusion date until progression per RECIST v1.1 as assessed by the investigator at local site, or death due to any cause.
  arm group label: AZD6422
  arm group type: Experimental
  description: It is anti-CLDN18.2 CAR-T cell therapy and the study consists of two parts: dose escalation (part 1) and dose expansion (part 2)
  intervention type: Biological
  intervention name: AZD6422 CLDN18.2 CAR-T product
  description: AZD6422 CAR-T product infusion after pre-conditioning
  arm group label: AZD6422
  other name: AZD6422
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Lin Shen, PHD
  role: Principal Investigator
  affiliation: Peking University Cancer Hospital & Institute
  last name: Lin Shen, PHD
  phone: 01088196090
  email: linshenpku@163.com
  facility: 
  contact: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Digestive System Neoplasms
  mesh term: Gastrointestinal Neoplasms
  sharing ipd: Yes
  ipd description: Qualified researchers can request access to anonymized individual patient-level data from sponsor or the collaborator group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the sponsor disclosure commitment. Yes, indicates that sponsors are accepting requests for IPD, but this does not mean all requests will be shared.
  ipd time frame: Sponsor or the collaborator group of companies will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please refer to disclosure commitment.
  ipd access criteria: When a request has been approved sponsor will provide access to the de-identified individual patient-level detain an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access.
  ipd url: https://vivli.org/