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/NCT06001580</url>
    </required_header>
    <id_info>
      <org_study_id>BR101-I</org_study_id>
      <nct_id>NCT06001580</nct_id>
    </id_info>
    <brief_title>A Phase I Study of BR101 Injection Alone in Subjects With Advanced Solid Tumors</brief_title>
    <official_title>A Phase Ia Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of BR101 Injection, as a Single Agent in Subjects With Advanced Solid Tumors</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Zhe Jiang Hisun Bioray Bio-pharmaceu tical Co.Ltd</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Zhe Jiang Hisun Bioray Bio-pharmaceu tical 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 a phase Ia study of single drug BR101 for Advanced solid tumor. The main&#xD;
        purpose of this study is to Evaluate the safety and tolerability of BR101monotherapy (single&#xD;
        dose and multiple doses) in Subjects with Advanced Solid Tumors and determine the MTD if&#xD;
        possible, and determine the RP2D.&#xD;
  &#xD;
        The secondary purpose of this study is to explore the Pharmacokinetics, Immunogenicity,&#xD;
        Antitumor Activity of BR101 monotherapy (single dose and multiple doses) in Subjects with&#xD;
        Advanced Solid Tumors&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">August 11, 2021</start_date>
    <completion_date type="Anticipated">June 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">December 31, 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>Safety, Tolerability,RP2D</measure>
      <time_frame>up to 91 days after the last administration</time_frame>
      <description>The incidence and severity of various adverse events of DLT, evaluated per NCI CTCAE 5.0 standard, abnormal physical examination, vital signs, laboratory examination, 12-guided ECG, etc.; maximum tolerated dose (MTD)(if possible).&#xD;
  Recommended Phase II clinical trial dose</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Cmax</measure>
      <time_frame>From screening to 31 days after the last administration</time_frame>
      <description>Cmax</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Tmax</measure>
      <time_frame>From screening to 31 days after the last administration</time_frame>
      <description>Tmax</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUC0-last</measure>
      <time_frame>From screening to 31 days after the last administration</time_frame>
      <description>AUC0-last</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>AUC0-tau</measure>
      <time_frame>From screening to 31 days after the last administration</time_frame>
      <description>AUC0-tau</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Cmin</measure>
      <time_frame>From screening to 31 days after the last administration</time_frame>
      <description>Cmin</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Immunogenicity assessment</measure>
      <time_frame>From screening to 31 days after the last administration</time_frame>
      <description>Anti-drug antibody (ADA) level produced by subjects</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>up to end of day 71</time_frame>
      <description>DCR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DoR</measure>
      <time_frame>up to end of day 71</time_frame>
      <description>DoR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>TTR</measure>
      <time_frame>up to end of day 71</time_frame>
      <description>TTR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>CR</measure>
      <time_frame>up to end of day 71</time_frame>
      <description>CR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PFS</measure>
      <time_frame>up to end of day 71</time_frame>
      <description>PFS</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate(ORR)</measure>
      <time_frame>up to end of day 71</time_frame>
      <description>ORR</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pharmacodynamic assessment</measure>
      <time_frame>UP to end of day 102</time_frame>
      <description>After administration, to evaluate Total/free CD73 level in peripheral blood, CD73 enzymatic activity in peripheral blood, CD73 level and CD73 occupancy of peripheral blood T lymphocytes, CD73 level and CD73 occupancy of tumor tissue, CD73 enzymatic activity in tumor tissue, CD8+ tumor infiltrating lymphocyte level in tumor tissue.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">36</enrollment>
    <condition>Advanced Solid Tumor</condition>
    <arm_group>
      <arm_group_label>BR101</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BR101</intervention_name>
      <description>BR101 injection was administered once for 28 days observation period and then weekly until the subject experienced unacceptable toxicity, disease progression, poor compliance, pregnancy, informed withdrawal, death, study interruption, and withdrawal from the study</description>
      <arm_group_label>BR101</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Patients who voluntarily sign the informed consent form with an understanding of the&#xD;
               nature, purpose and procedures of the trial, and can comply the protocol; 2. Males and&#xD;
               females with an age of or above 18 years; 3. Patients with advanced or metastatic&#xD;
               solid tumors diagnosed by pathological histology and / or cytology (cell wax only) who&#xD;
               are unable for radical surgical resection, or who have failed to standard treatment or&#xD;
               who have been intolerant to standard treatment (disease progression, or intolerant to&#xD;
               chemotherapy, targeted therapy, etc.), or who lack effective treatment; 4. At least&#xD;
               one measurable lesion according to RECIST V1.1; 5. ECOG score ≤ 1; 6. A recovery of&#xD;
               previous treatment releated toxic reactions (except for the residual hair loss effect)&#xD;
               to or under Grade 1 (according to CTCAE v 5.0) and a complete recovery of the&#xD;
               immune-related adverse effects if the patients received anti-tumor treatment before;&#xD;
               7. Sufficient organ and bone marrow function; 8. The expected survival above 12 weeks;&#xD;
               9. Blood HCG test of females with a reproductive potential should be negative; 10.&#xD;
               Fertile men and women must use a highly effective contraceptive methods, and continue&#xD;
               the birth control for six months after the last dose.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  . An current active autoimmune disease or history; 2. A history of primary&#xD;
               immunodeficiency; 3. An current interstitial lung disease or history (except local&#xD;
               interstitial lung disease induced by radiotherapy); 4. An active tuberculosis or&#xD;
               history; 5. Any active infection that requires systemic treatment through intravenous&#xD;
               infusion within 14 days before first dose; 6. Two or more primary tumors (excluding&#xD;
               cured cervical in situ carcinoma, basal cell carcinoma or squamous cell skin cancer,&#xD;
               and other tumors that have been treated and stable for more than 5 years); 7.&#xD;
               Symptomatic or untreated metastasis in brain or other central nervous system. However,&#xD;
               patients with CNS matastasis that has been completed removed and/or be stable or&#xD;
               relieved after radiotherapy can be enrolled; 8. Uncontrollable pleural fluid, ascites,&#xD;
               or pericardial effusion assesed by the investigator; 9. Patients with any of the&#xD;
               following heart diseases: any grade of heart failure assesed by NYHA, severe cardiac&#xD;
               arrhythmias requiring treatment, Unstable angina pectoris，myocardial infarction&#xD;
               occurred within 3 months before the first dose, QTc≥480 ms, hypertension that cannot&#xD;
               in good control, receiving PTCA or CABG within 6 months before the first dose; 10.&#xD;
               Patients received anti-tumor therapy or participated in other clinical studies and&#xD;
               used other test drugs 28 days before the first dose; Patients received the traditional&#xD;
               Chinese medicine within 7 days before the first dose; 11. A history of psychopathy;&#xD;
               12. A history of major surgery or radiotherapy within 28 days before the first dose or&#xD;
               expecting to operate a major surgery during the trial, a history of therapeutic&#xD;
               radioactive agents within 56 days prior to the first dose; 13. A history of allogeneic&#xD;
               organ transplantation or allogeneic hematopoietic stem cell transplantation; 14.&#xD;
               Patients who have a bleeding tendency or are receiving thrombolytic or anticoagulant&#xD;
               therapy; 15. Patients who had been vaccinated within 28 days before the first dose or&#xD;
               intend to be vaccinated during the trial; 16. Patients who had a history of blood&#xD;
               donation within 3 months before the first dose, or plan to donate blood during the&#xD;
               trial; 17. Patients who need to receive corticosteroids for more than 7 days&#xD;
               (methylprednisolone &gt; 10 mg/d or the equivalent dose) or other immunosuppressants&#xD;
               within 14 days before the first dose, except for inhaled corticosteroids; 18. Patients&#xD;
               with a positive presence in terms of antibody to human immunodeficiency virus should&#xD;
               be excluded; patients with a positive treponema pallidum specific antibody test&#xD;
               require a further testing of the treponema pallidum non-specific antibody, and if the&#xD;
               result is also positive, the subject shoule be excluded; patients with a positive&#xD;
               hepatitis C virus antibody test require a further testing of the hepatitis C virus RNA&#xD;
               [HCV RNA], and if the result is also positive, the subject shoule be excluded;&#xD;
               patients with a positive hepatitis B virus antibody test require a further testing of&#xD;
               the hepatitis B virus DNA [HBV DNA], and if the result is also positive, the subject&#xD;
               shoule be excluded; 19. Patients with diseases affecting intravenous injection and&#xD;
               blood sample collection; 20. Pregnant or lactating women; 21. A plan to donate sperm&#xD;
               from the signing of ICF to 6 months after the last dose; 22. A situation or a&#xD;
               possibility that patients can't comply the protocal; 23. Other situations that are not&#xD;
               suitable to attend this trial assesed by the investigator.&#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_contact>
      <last_name>Jian Huang, PhD</last_name>
      <phone>(+86)0571-87783759</phone>
      <email>hjys@zju.edu.cn</email>
    </overall_contact>
    <location>
      <facility>
        <name>The Second Affiliated Hospital of Zhejiang University Medical College</name>
        <address>
          <city>Hangzhou</city>
          <state>Zhejiang</state>
          <zip>310052</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jian Huang, PhD</last_name>
        <phone>(+86)0571-87783759</phone>
        <email>hjys@zju.edu.cn</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 4, 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>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
    </condition_browse>
    <!-- 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/NCT06001580
  org study id: BR101-I
  nct id: NCT06001580
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study is a phase Ia study of single drug BR101 for Advanced solid tumor. The main
        purpose of this study is to Evaluate the safety and tolerability of BR101monotherapy (single
        dose and multiple doses) in Subjects with Advanced Solid Tumors and determine the MTD if
        possible, and determine the RP2D.
  
        The secondary purpose of this study is to explore the Pharmacokinetics, Immunogenicity,
        Antitumor Activity of BR101 monotherapy (single dose and multiple doses) in Subjects with
        Advanced Solid Tumors
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Safety, Tolerability,RP2D
  time frame: up to 91 days after the last administration
  description: The incidence and severity of various adverse events of DLT, evaluated per NCI CTCAE 5.0 standard, abnormal physical examination, vital signs, laboratory examination, 12-guided ECG, etc.; maximum tolerated dose (MTD)(if possible).
  Recommended Phase II clinical trial dose
  measure: Cmax
  time frame: From screening to 31 days after the last administration
  description: Cmax
  measure: Tmax
  time frame: From screening to 31 days after the last administration
  description: Tmax
  measure: AUC0-last
  time frame: From screening to 31 days after the last administration
  description: AUC0-last
  measure: AUC0-tau
  time frame: From screening to 31 days after the last administration
  description: AUC0-tau
  measure: Cmin
  time frame: From screening to 31 days after the last administration
  description: Cmin
  measure: Immunogenicity assessment
  time frame: From screening to 31 days after the last administration
  description: Anti-drug antibody (ADA) level produced by subjects
  measure: DCR
  time frame: up to end of day 71
  description: DCR
  measure: DoR
  time frame: up to end of day 71
  description: DoR
  measure: TTR
  time frame: up to end of day 71
  description: TTR
  measure: CR
  time frame: up to end of day 71
  description: CR
  measure: PFS
  time frame: up to end of day 71
  description: PFS
  measure: Objective response rate(ORR)
  time frame: up to end of day 71
  description: ORR
  measure: Pharmacodynamic assessment
  time frame: UP to end of day 102
  description: After administration, to evaluate Total/free CD73 level in peripheral blood, CD73 enzymatic activity in peripheral blood, CD73 level and CD73 occupancy of peripheral blood T lymphocytes, CD73 level and CD73 occupancy of tumor tissue, CD73 enzymatic activity in tumor tissue, CD8+ tumor infiltrating lymphocyte level in tumor tissue.
  arm group label: BR101
  arm group type: Experimental
  intervention type: Drug
  intervention name: BR101
  description: BR101 injection was administered once for 28 days observation period and then weekly until the subject experienced unacceptable toxicity, disease progression, poor compliance, pregnancy, informed withdrawal, death, study interruption, and withdrawal from the study
  arm group label: BR101
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Jian Huang, PhD
  phone: (+86)0571-87783759
  email: hjys@zju.edu.cn
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Neoplasms