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/NCT06001684</url>
    </required_header>
    <id_info>
      <org_study_id>IBR854-101</org_study_id>
      <nct_id>NCT06001684</nct_id>
    </id_info>
    <brief_title>Phase 1 Study of IBR854 in Locally Advanced Or Metastatic Solid Tumors</brief_title>
    <official_title>A Phase I Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of IBR854 Cell Injection in Patients With Unresectable Locally Advanced Or Metastatic Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Imbioray (Hangzhou) Biomedicine Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Imbioray (Hangzhou) Biomedicine Co., Ltd.</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 study is an open-label, phase I study to evaluate the safety, tolerability,&#xD;
        pharmacokinetics (PK), and preliminary efficacy of IBR854 cell injection in patients with&#xD;
        unresectable, locally advanced, or metastatic solid tumors.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study is a dose escalation study which adopts the 3+3 dose escalation design protocol.&#xD;
        The dose is respectively 3.0×10^9 cells, 5.0×10^9 cells and 7.0×10^9 cells. The&#xD;
        administration is performed on day 1 and day 8 of each cycle (21 days). 3-6 subjects will be&#xD;
        enrolled at every dose level. The first and second subjects in the same group shall be&#xD;
        enrolled at an interval of at least 7 days, for the purpose of ensuring their safety. Only&#xD;
        when the dose-limiting toxicity (DLT) of all subjects in the previous dose group was observed&#xD;
        can the enrollment of the next dose group get started.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2024</completion_date>
    <primary_completion_date type="Anticipated">September 30, 2024</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 dose limiting toxicity (DLTs)</measure>
      <time_frame>From day1 to day 21</time_frame>
      <description>To collect dose limiting toxicities (DLTs) occurring within 21 days after the first dose</description>
    </primary_outcome>
    <primary_outcome>
      <measure>The incidence and severity of adverse events (AEs)</measure>
      <time_frame>From day 1 to day 90 after the first dose</time_frame>
      <description>To evaluate the safety of IBR854 cell injection</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR)</measure>
      <time_frame>1 year</time_frame>
      <description>To determine the anti-tumor effectivity of IBR854 cell injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease control rate (DCR)</measure>
      <time_frame>1 year</time_frame>
      <description>To determine the anti-tumor effectivity of IBR854 cell injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of remission (DOR)</measure>
      <time_frame>1 year</time_frame>
      <description>To determine the anti-tumor effectivity of IBR854 cell injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progression-free survival (PFS)</measure>
      <time_frame>1 year</time_frame>
      <description>To determine the anti-tumor effectivity of IBR854 cell injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS)</measure>
      <time_frame>1 year</time_frame>
      <description>To determine the anti-tumor effectivity of IBR854 cell injection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The number of IBR854 cells</measure>
      <time_frame>1 year</time_frame>
      <description>Blood samples will be collected at specified time points to detect the number of IBR854 cells in peripheral blood</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Anti-CAR antibodies</measure>
      <time_frame>1 year</time_frame>
      <description>Blood samples will be collected at specified time points to detect anti-CAR(anti-5T4 mAb) antibodies</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">18</enrollment>
    <condition>Solid Tumors</condition>
    <arm_group>
      <arm_group_label>IBR854 Cell Injection</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The minimum initial dose is 3.0×10^9 cells and then escalate to 5.0×10^9 cells and 7.0×10^9 cells. Every 21 days is one cycle, and intravenous infusion is performed on day 1 and day 8 of each cycle.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>IBR854 Cell Injection</intervention_name>
      <description>The minimum initial dose is 3.0×10^9 cells and then escalate to 5.0×10^9 cells and 7.0×10^9 cells. Every 21 days is one cycle, and intravenous infusion is performed on day 1 and day 8 of each cycle.</description>
      <arm_group_label>IBR854 Cell Injection</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Subjects volunteer to participate in this clinical study, are fully aware of the study&#xD;
               and have signed the Informed Consent Form (ICF). Subjects are willing to follow and&#xD;
               able to complete all trial procedures.&#xD;
  &#xD;
            2. Age: adult at the age of 18-75 (both inclusive), female or male.&#xD;
  &#xD;
            3. Subjects with histologically or cytologically confirmed, unresectable, locally&#xD;
               advanced or metastatic solid tumors (which can be diagnosed with the use of tumor&#xD;
               markers in combination with imaging for specific advanced tumors, such as liver&#xD;
               cancer) who have no current standard of care.&#xD;
  &#xD;
            4. Eastern Cooperative Oncology Group (ECOG) score ≤2 and expected survival time &gt;3&#xD;
               months.&#xD;
  &#xD;
            5. According to the Response Evaluation Criteria in Solid Tumors (RECIST) V1.1 criteria,&#xD;
               the subjects have at least one target lesion (non-lymph node lesion with major&#xD;
               diameter ≥ 1.0cm or lymph node lesion with minor diameter ≥ 1.5 cm). A lesion that is&#xD;
               within the field of previous radiotherapy could not be considered a target unless&#xD;
               there is radiographic evidence of progression.&#xD;
  &#xD;
            6. Organ function during screening should meet the following criteria:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥1.5×10^9/L; Platelet (PLT) ≥75×10^9/L;&#xD;
                    Hemoglobin (Hb)≥80g/L (no blood transfusion or hematopoietic stimulator treatment&#xD;
                    within 7 days).&#xD;
  &#xD;
                 -  Alanine aminotransferase (ALT)≤3×ULN (Patients with liver metastasis: ≤5×ULN);&#xD;
                    Aspartate aminotransferase (AST)≤3×ULN (Patients with liver metastasis: ≤5×ULN);&#xD;
  &#xD;
                 -  Creatinine (Cr) ≤2× ULN; Creatinine clearance (Ccr) (to be calculated only when&#xD;
                    Cr &gt; 2× ULN) &gt; 50ml/min (Cockcroft-Gault formula);&#xD;
  &#xD;
                 -  Activated partial thrombin time (APTT) ≤1.5×ULN, International normalized ratio&#xD;
                    (INR) ≤1.5×ULN (Patients with anticoagulants: ≤ 2.5×ULN).&#xD;
  &#xD;
            7. Subjects of reproductive age and their partners should agree to have no family&#xD;
               planning and to use effective contraceptive methods for 6 months from signing the ICF&#xD;
               until the last dose of the study drug is administered.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Have received systemic antitumor therapy within 4 weeks or five half-lives of the drug&#xD;
               (whichever is longer) before the first dose of the study drug: Systemic chemotherapy&#xD;
               (2 weeks for oral fluorouracil, 6 weeks for mitomycin C and nitrosoureas), endocrine&#xD;
               therapy, targeted therapy (2 weeks or 5 half-life for small molecule targeted therapy,&#xD;
               whichever is longer), immunotherapy, radical radiotherapy, tumor embolization, Chinese&#xD;
               herbal medicine for anti-tumor indications, etc. Or received palliative radiotherapy&#xD;
               within 2 weeks before the first dose.&#xD;
  &#xD;
            2. Toxic effects from previous antitumor therapy have not returned to grade 1 or less&#xD;
               (other than alopecia or fatigue).&#xD;
  &#xD;
            3. Any prior adoptive cellular immunotherapy.&#xD;
  &#xD;
            4. Active brain metastases (one of the following criteria: clinical symptoms; A new&#xD;
               diagnosis; Progression after previous local treatment).&#xD;
  &#xD;
            5. Have undergone major organ surgery within 4 weeks prior to their first use of the&#xD;
               study drug, or required elective surgery during the study period.&#xD;
  &#xD;
            6. Long-term (≥ 3 days) treatment with a glucocorticoid (prednisone &gt; 10 mg per day or&#xD;
               equivalent) or another immunosuppressive agent is anticipated to be required during&#xD;
               the study. Inhaled or topical steroid hormones are allowed in subjects without active&#xD;
               autoimmune disease&#xD;
  &#xD;
            7. Have received a live or attenuated vaccine within 4 weeks before the first dose or&#xD;
               plan to receive a live or attenuated vaccine during the study period.&#xD;
  &#xD;
            8. Have severe infections that cannot be controlled.&#xD;
  &#xD;
            9. Active hepatitis B, hepatitis C virus infection or HIV infection.&#xD;
  &#xD;
           10. Have undergone an allogeneic bone marrow transplant or other organ transplant.&#xD;
  &#xD;
           11. Have active autoimmune diseases or have had autoimmune diseases that are likely to&#xD;
               recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel&#xD;
               disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.). Except in the&#xD;
               following cases: type 1 diabetes that was well controlled with hormone replacement&#xD;
               therapy, hypothyroidism, skin conditions that did not require systemic therapy (e.g.,&#xD;
               vitiligo), and other conditions that were well controlled and that the investigator&#xD;
               determined were less likely to recur (e.g., childhood asthma in remission).&#xD;
  &#xD;
           12. Have a history of serious cardiovascular and cerebrovascular diseases, including but&#xD;
               not limited to:&#xD;
  &#xD;
                 -  There are serious cardiac rhythm or conduction abnormalities, such as ventricular&#xD;
                    arrhythmia, and Ⅱ-Ⅲ degree atrioventricular block, which need clinical&#xD;
                    intervention;&#xD;
  &#xD;
                 -  Prolonged QT interval corrected with Fridericia's method (QTcF) (&gt;450 ms in men;&#xD;
                    &gt;470 ms for women)&#xD;
  &#xD;
                 -  Acute coronary syndrome, congestive heart failure, aortic dissection, stroke, or&#xD;
                    other grade 3 or above cardiovascular and cerebrovascular events occurring within&#xD;
                    6 months before the first administration;&#xD;
  &#xD;
                 -  Patients with heart failure or left ventricular ejection fraction (LVEF) &lt; 50% in&#xD;
                    the New York Heart Association (NYHA) classification ≥II;&#xD;
  &#xD;
                 -  Hypertension beyond clinical control.&#xD;
  &#xD;
           13. Clinically significant chronic obstructive pulmonary disease or other moderate to&#xD;
               severe chronic respiratory disease developed within 6 months.&#xD;
  &#xD;
           14. Have other malignant tumors in the past 3 years, excluding skin basal cell carcinoma,&#xD;
               ductal carcinoma in situ and cervical carcinoma in situ with a radical surgery.&#xD;
  &#xD;
           15. Pregnant or lactating women.&#xD;
  &#xD;
           16. Have mental disorders or a history of alcohol, drug or drug abuse within one year.&#xD;
  &#xD;
           17. Have participated in other clinical trials and received any unmarketed investigational&#xD;
               drug or treatment within 4 weeks prior to first use of the study drug.&#xD;
  &#xD;
           18. Allergic to the main components of the study drug.&#xD;
  &#xD;
           19. The investigator considered that the subjects had a history of other serious systemic&#xD;
               diseases or other reasons that made them unsuitable for the study.&#xD;
  &#xD;
           20. Unsuitable for participation in this study considered by the investigators.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Ning Li, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Ning Li, MD, PhD</last_name>
      <phone>+86-010-87788787</phone>
      <email>cancergcp@163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Shuhang Wang, MD, PhD</last_name>
      <phone>+86-010-87788787</phone>
      <email>cancergcp@163.com</email>
    </overall_contact_backup>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 14, 2023</last_update_submitted>
    <last_update_submitted_qc>August 14, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 21, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</investigator_affiliation>
      <investigator_full_name>Ning Li</investigator_full_name>
      <investigator_title>MD, PhD</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>
  
  
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/NCT06001684
  org study id: IBR854-101
  nct id: NCT06001684
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study is an open-label, phase I study to evaluate the safety, tolerability,
        pharmacokinetics (PK), and preliminary efficacy of IBR854 cell injection in patients with
        unresectable, locally advanced, or metastatic solid tumors.
  This study is a dose escalation study which adopts the 3+3 dose escalation design protocol.
        The dose is respectively 3.0×10^9 cells, 5.0×10^9 cells and 7.0×10^9 cells. The
        administration is performed on day 1 and day 8 of each cycle (21 days). 3-6 subjects will be
        enrolled at every dose level. The first and second subjects in the same group shall be
        enrolled at an interval of at least 7 days, for the purpose of ensuring their safety. Only
        when the dose-limiting toxicity (DLT) of all subjects in the previous dose group was observed
        can the enrollment of the next dose group get started.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Incidence of dose limiting toxicity (DLTs)
  time frame: From day1 to day 21
  description: To collect dose limiting toxicities (DLTs) occurring within 21 days after the first dose
  measure: The incidence and severity of adverse events (AEs)
  time frame: From day 1 to day 90 after the first dose
  description: To evaluate the safety of IBR854 cell injection
  measure: Objective response rate (ORR)
  time frame: 1 year
  description: To determine the anti-tumor effectivity of IBR854 cell injection
  measure: Disease control rate (DCR)
  time frame: 1 year
  description: To determine the anti-tumor effectivity of IBR854 cell injection
  measure: Duration of remission (DOR)
  time frame: 1 year
  description: To determine the anti-tumor effectivity of IBR854 cell injection
  measure: Progression-free survival (PFS)
  time frame: 1 year
  description: To determine the anti-tumor effectivity of IBR854 cell injection
  measure: Overall survival (OS)
  time frame: 1 year
  description: To determine the anti-tumor effectivity of IBR854 cell injection
  measure: The number of IBR854 cells
  time frame: 1 year
  description: Blood samples will be collected at specified time points to detect the number of IBR854 cells in peripheral blood
  measure: Anti-CAR antibodies
  time frame: 1 year
  description: Blood samples will be collected at specified time points to detect anti-CAR(anti-5T4 mAb) antibodies
  arm group label: IBR854 Cell Injection
  arm group type: Experimental
  description: The minimum initial dose is 3.0×10^9 cells and then escalate to 5.0×10^9 cells and 7.0×10^9 cells. Every 21 days is one cycle, and intravenous infusion is performed on day 1 and day 8 of each cycle.
  intervention type: Biological
  intervention name: IBR854 Cell Injection
  description: The minimum initial dose is 3.0×10^9 cells and then escalate to 5.0×10^9 cells and 7.0×10^9 cells. Every 21 days is one cycle, and intravenous infusion is performed on day 1 and day 8 of each cycle.
  arm group label: IBR854 Cell Injection
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Ning Li, MD, PhD
  role: Principal Investigator
  affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  last name: Ning Li, MD, PhD
  phone: +86-010-87788787
  email: cancergcp@163.com
  last name: Shuhang Wang, MD, PhD
  phone: +86-010-87788787
  email: cancergcp@163.com
  responsible party type: Principal Investigator
  investigator affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
  investigator full name: Ning Li
  investigator title: MD, PhD
  mesh term: Neoplasms
  sharing ipd: No