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/NCT05975645</url>
    </required_header>
    <id_info>
      <org_study_id>TQB2618-AK105-Ib-04</org_study_id>
      <nct_id>NCT05975645</nct_id>
    </id_info>
    <brief_title>A Clinical Study of TQB2618 Injection Combined With Penpulimab Injection and Anlotinib Hydrochloride Capsules for First-line Treatment of Advanced Hepatocellular Carcinoma (HCC).</brief_title>
    <official_title>A Phase Ib Clinical Study to Evaluate the Efficacy and Safety of TQB2618 Injection Combined With Penpulimab Injection and Anlotinib Hydrochloride Capsules as First-line Treatment for Advanced Hepatocellular Carcinoma.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Chia Tai Tianqing Pharmaceutical Group Co., Ltd.</source>
    <oversight_info>
      <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 an open, single-arm, multi-center clinical study designed to evaluate the efficacy&#xD;
        and safety of TQB2618 injection combined with penpulimab injection and Anlotinib&#xD;
        Hydrochloride Capsules in patients with advanced HCC.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">April 2025</completion_date>
    <primary_completion_date type="Anticipated">December 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>Overall response rate (ORR)</measure>
      <time_frame>Up to 2 years.</time_frame>
      <description>Percentage of subjects achieving complete response (CR) and partial response (PR).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Up to two and a half years.</time_frame>
      <description>OS is defined as the time from the first time the subject received treatment to death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Progress Free Survival (PFS)</measure>
      <time_frame>Up to 2 years.</time_frame>
      <description>The time from the first administration of the drug to disease progression or death (whichever occurs first).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease Control Rate (DCR)</measure>
      <time_frame>Up to 2 years.</time_frame>
      <description>Percentage of subjects achieving CR and PR and stable disease (SD) is greater than or equal to 4-6 weeks.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of Response (DOR)</measure>
      <time_frame>Up to 2 years.</time_frame>
      <description>The time from the first assessment of the tumor's CR or PR to the disease's first progression or death from various causes.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Anti-Drug antibody (ADA)</measure>
      <time_frame>Before administration on the first day of the 1st, 2nd, 4th, and 8th cycles, 30 days and 90 days after the last administration. Each cycle is 21 days.</time_frame>
      <description>The incidence of ADA after the administration of TQB2618.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of neutralizing antibodies (Nab)</measure>
      <time_frame>Before administration on the first day of the 1st, 2nd, 4th, and 8th cycles, 30 days and 90 days after the last administration. Each cycle is 21 days.</time_frame>
      <description>The incidence of Nab after the administration of TQB2618.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of adverse events (AEs)</measure>
      <time_frame>Baseline up to 2 years.</time_frame>
      <description>All adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Severity of adverse events (AEs)</measure>
      <time_frame>Baseline up to 2 years.</time_frame>
      <description>All adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Incidence of Serious adverse events (SAEs)</measure>
      <time_frame>Baseline up to 2 years.</time_frame>
      <description>It refers to adverse medical events such as death, life-threatening, permanent, or serious disability or loss of function, hospitalization or prolonged hospitalization, and congenital abnormalities or birth defects after the subject receives the experimental drug.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">40</enrollment>
    <condition>Advanced Hepatocellular Carcinoma</condition>
    <arm_group>
      <arm_group_label>TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Intravenous infusion of TQB2618 Injection 1200mg and Penpulimab Injection 200mg on 1st day, combining with Anlotinib capsules 10mg given orally in fasting conditions once daily in each 21-day cycle. (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Penpulimab injection</intervention_name>
      <description>Penpulimab is an inhibitor of programmed cell death 1 (PD-1).</description>
      <arm_group_label>TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TQB2618 injection</intervention_name>
      <description>TQB2618 injection is an inhibitor of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3).</description>
      <arm_group_label>TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Anlotinib Hydrochloride Capsules</intervention_name>
      <description>Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.</description>
      <arm_group_label>TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18-75 years old; Eastern Cooperative Oncology Group (ECOG) performance status score of&#xD;
               0 or 1; Life expectancy ≥ 3 months.&#xD;
  &#xD;
            -  Patients with HCC diagnosed by histopathological or cytological examination or in line&#xD;
               with clinical diagnostic criteria.&#xD;
  &#xD;
            -  No systematic treatment for advanced HCC has been received before.&#xD;
  &#xD;
            -  China liver cancer staging (CNLC)stage III or Barcelona Clinic Liver Cancer (BCLC)&#xD;
               stage C, or CNLC stage II (BCLC B) subjects who are not suitable for local treatment&#xD;
               and surgical treatment, or who are judged by researchers to be unable to benefit from&#xD;
               local treatment and surgical treatment.&#xD;
  &#xD;
            -  Child-Pugh liver function classification: A or B (≤7 points).&#xD;
  &#xD;
            -  Hepatitis B surface antigen (HBsAg) positive patients must meet hepatitis B virus&#xD;
               deoxyribonucleic acid (HBV DNA) quantification &lt; 10000 IU / ml (or 50000 copy/ml), and&#xD;
               anti-HBV therapy should be given for at least 1 week before the first administration;&#xD;
               investigator needs to determine that hepatitis C virus (HCV) infection is in a stable&#xD;
               state.&#xD;
  &#xD;
            -  Patients after local treatment should be administered at least 4 weeks after the end&#xD;
               of local treatment and have fully recovered from treatment toxicity and/or&#xD;
               complications.&#xD;
  &#xD;
            -  Radiotherapy for bone metastases accompanied by clinical symptoms must be completed at&#xD;
               least 2 weeks before the first administration.&#xD;
  &#xD;
            -  Has at least one measurable lesion.&#xD;
  &#xD;
            -  The Main organ function is normal.&#xD;
  &#xD;
            -  Men and women of childbearing age should agree to use contraceptive measures (such as&#xD;
               intrauterine devices, contraceptives, or condoms) during the study period and within 6&#xD;
               months after the end of the study. Serum human chorionic gonadotropin (HCG) test is&#xD;
               not negative within 7 days before the first administration and must be non-lactating&#xD;
               patients.&#xD;
  &#xD;
            -  Voluntary and signed informed consent, good compliance.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Combined disease and medical history :&#xD;
  &#xD;
                 1. Other malignant tumors had appeared or were suffering from at the same time&#xD;
                    within 3 years before the first administration.&#xD;
  &#xD;
                 2. Unrelieved toxic reactions higher than grade 1 due to any previous treatment.&#xD;
  &#xD;
                 3. Major surgical treatment, obvious traumatic injury, or long-term unhealed wounds&#xD;
                    or fractures were received within 28 days before the first administration.&#xD;
  &#xD;
                 4. Patients who had any bleeding or bleeding events ≥grade 3 within 4 weeks before&#xD;
                    the first administration, or had arterial/venous thrombosis events within 6&#xD;
                    months before the first administration.&#xD;
  &#xD;
                 5. There was a history of gastrointestinal bleeding within 6 months before the first&#xD;
                    administration; other conditions that may cause gastrointestinal bleeding or&#xD;
                    perforation.&#xD;
  &#xD;
                 6. Patients with portal hypertension have a high risk of bleeding, or gastroscopy&#xD;
                    confirmed red sign or severe esophageal and gastric varices.&#xD;
  &#xD;
                 7. Active pulmonary tuberculosis, history of idiopathic pulmonary fibrosis,&#xD;
                    organizing pneumonia, drug-induced pneumonia, radiation pneumonitis requiring&#xD;
                    treatment, or active pneumonia with clinical symptoms.&#xD;
  &#xD;
                 8. Have a history of mental drug abuse that cannot be withdrawn, or have a mental&#xD;
                    disorder.&#xD;
  &#xD;
                 9. Patients who had previously received or planned to receive allogeneic bone marrow&#xD;
                    transplantation or solid organ transplantation within 6 months.&#xD;
  &#xD;
                10. Have a history of hepatic encephalopathy.&#xD;
  &#xD;
                11. Currently using or recently used aspirin (&gt;325mg/day) or dipyridamole,&#xD;
                    ticlopidine, clopidogrel, and cilostazol treatment.&#xD;
  &#xD;
                12. Have any heavy and/or uncontrolled disease.&#xD;
  &#xD;
            -  Tumor-related, previous, and current treatment:&#xD;
  &#xD;
                 1. Histopathology or cytology confirmed as fibrolamellar hepatocellular carcinoma,&#xD;
                    sarcomatoid hepatocellular carcinoma, hepatobiliary cell carcinoma, mixed liver&#xD;
                    cancer, etc&#xD;
  &#xD;
                 2. According to imaging examination, there was portal vein tumor thrombus involving&#xD;
                    the trunk; or inferior vena cava tumor thrombus or heart involvement.&#xD;
  &#xD;
                 3. Subjects have been treated with immune checkpoint inhibitors such as programmed&#xD;
                    cell death protein 1 (PD-1), Programmed cell death 1 ligand 1(PD-L1), T cell&#xD;
                    immunoglobulin and mucin domain containing protein 3 (TIM-3), etc.&#xD;
  &#xD;
                 4. Previously received any type of cellular immunotherapy.&#xD;
  &#xD;
                 5. Has uncontrolled pleural effusion, pericardial effusion, or ascites requiring&#xD;
                    repeated drainage.&#xD;
  &#xD;
                 6. Suffering from spinal cord compression, cancerous meningitis, with symptoms of&#xD;
                    brain metastasis or symptoms control time less than 4 weeks.&#xD;
  &#xD;
            -  Study-related treatment:&#xD;
  &#xD;
                 1. There was a history of attenuated live vaccine inoculation within 28 days before&#xD;
                    the first administration, or attenuated live vaccine inoculation was planned&#xD;
                    during the study period.&#xD;
  &#xD;
                 2. Severe hypersensitivity reaction occurred after using macromolecular drugs.&#xD;
  &#xD;
                 3. Those with multiple factors affecting the oral administration of drugs.&#xD;
  &#xD;
                 4. Active autoimmune diseases requiring systemic treatment occurred within 2 years&#xD;
                    before the first administration.&#xD;
  &#xD;
                 5. immunodeficiency, or Undergoing systemic glucocorticoid therapy or any other form&#xD;
                    of immunosuppressive therapy.&#xD;
  &#xD;
            -  Those who participated in and used other anti-tumor clinical trial drugs within 4&#xD;
               weeks before the first administration.&#xD;
  &#xD;
            -  According to the judgment of the investigators, some situations seriously endanger the&#xD;
               safety of the subjects or affect the subjects to complete the study.&#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_contact>
      <last_name>Qiang Xia, Doctor</last_name>
      <phone>+86 13661889035</phone>
      <email>Xiaqiang@medmail.com.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Hao Feng, Doctor</last_name>
      <phone>+86 15000901110</phone>
      <email>Fenghao@renji.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Gansu Wuwei Cancer Hospital</name>
        <address>
          <city>Wuwei</city>
          <state>Gansu</state>
          <zip>733099</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Wenhua Zhang, Bachelor</last_name>
        <phone>+86 18993531188</phone>
        <email>925944468@qq.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>The Third Affiliated Hospital of Sun Yat-sen University</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510600</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Hua Li, Doctor</last_name>
        <phone>+86 13060975202</phone>
        <email>lihua100@yeah.net</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Affiliated hospital of zunyi medical university</name>
        <address>
          <city>Zunyi</city>
          <state>Guizhou</state>
          <zip>563099</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Rongshu Shi, Doctor</last_name>
        <phone>+86 13985263013</phone>
        <email>shirongshujieru@163.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Affiliated Cancer Hospital of Harbin Medical University</name>
        <address>
          <city>Harbin</city>
          <state>Heilongjiang</state>
          <zip>150000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Tongsen Zheng, Doctor</last_name>
        <phone>+86 15134569619</phone>
        <email>zhengtongsen@126.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>The First People's Hospital of Shangqiu City</name>
        <address>
          <city>Shangqiu</city>
          <state>Henan</state>
          <zip>476100</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Gongbin Chen, Bachelor</last_name>
        <phone>+86 13937062760</phone>
        <email>Chengongbin@sina.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Hunan Cancer Hospital</name>
        <address>
          <city>Changsha</city>
          <state>Hunan</state>
          <zip>410031</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Jia Luo, Doctor</last_name>
        <phone>+86 13874994359</phone>
        <email>luojia@hnca.org.cn</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>The six people's Hospital of Shenyang</name>
        <address>
          <city>Shenyang</city>
          <state>Liaoning</state>
          <zip>110000</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Wei Wu, Master</last_name>
        <phone>+86 18502460420</phone>
        <email>wuwei19700420@sina.com</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>Third Affiliated Hospital of Naval Medical University</name>
        <address>
          <city>Shanghai</city>
          <state>Shanghai</state>
          <zip>200433</zip>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Kui Wang, Doctor</last_name>
        <phone>+86 13636330827</phone>
        <email>wangkuiykl@163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>May 2023</verification_date>
    <study_first_submitted>July 27, 2023</study_first_submitted>
    <study_first_submitted_qc>July 27, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 4, 2023</study_first_posted>
    <last_update_submitted>July 27, 2023</last_update_submitted>
    <last_update_submitted_qc>July 27, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 4, 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>Carcinoma</mesh_term>
      <mesh_term>Carcinoma, Hepatocellular</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/NCT05975645
  org study id: TQB2618-AK105-Ib-04
  nct id: NCT05975645
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is an open, single-arm, multi-center clinical study designed to evaluate the efficacy
        and safety of TQB2618 injection combined with penpulimab injection and Anlotinib
        Hydrochloride Capsules in patients with advanced HCC.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Overall response rate (ORR)
  time frame: Up to 2 years.
  description: Percentage of subjects achieving complete response (CR) and partial response (PR).
  measure: Overall Survival (OS)
  time frame: Up to two and a half years.
  description: OS is defined as the time from the first time the subject received treatment to death due to any cause.
  measure: Progress Free Survival (PFS)
  time frame: Up to 2 years.
  description: The time from the first administration of the drug to disease progression or death (whichever occurs first).
  measure: Disease Control Rate (DCR)
  time frame: Up to 2 years.
  description: Percentage of subjects achieving CR and PR and stable disease (SD) is greater than or equal to 4-6 weeks.
  measure: Duration of Response (DOR)
  time frame: Up to 2 years.
  description: The time from the first assessment of the tumor's CR or PR to the disease's first progression or death from various causes.
  measure: Incidence of Anti-Drug antibody (ADA)
  time frame: Before administration on the first day of the 1st, 2nd, 4th, and 8th cycles, 30 days and 90 days after the last administration. Each cycle is 21 days.
  description: The incidence of ADA after the administration of TQB2618.
  measure: Incidence of neutralizing antibodies (Nab)
  time frame: Before administration on the first day of the 1st, 2nd, 4th, and 8th cycles, 30 days and 90 days after the last administration. Each cycle is 21 days.
  description: The incidence of Nab after the administration of TQB2618.
  measure: Incidence of adverse events (AEs)
  time frame: Baseline up to 2 years.
  description: All adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).
  measure: Severity of adverse events (AEs)
  time frame: Baseline up to 2 years.
  description: All adverse medical events that occur after the subject receives the investigational drug, evaluated according to the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE v5.0).
  measure: Incidence of Serious adverse events (SAEs)
  time frame: Baseline up to 2 years.
  description: It refers to adverse medical events such as death, life-threatening, permanent, or serious disability or loss of function, hospitalization or prolonged hospitalization, and congenital abnormalities or birth defects after the subject receives the experimental drug.
  arm group label: TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules
  arm group type: Experimental
  description: Intravenous infusion of TQB2618 Injection 1200mg and Penpulimab Injection 200mg on 1st day, combining with Anlotinib capsules 10mg given orally in fasting conditions once daily in each 21-day cycle. (14 days on treatment from Day 1-14, 7 days off treatment from Day 15-21)
  intervention type: Drug
  intervention name: Penpulimab injection
  description: Penpulimab is an inhibitor of programmed cell death 1 (PD-1).
  arm group label: TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules
  intervention type: Drug
  intervention name: TQB2618 injection
  description: TQB2618 injection is an inhibitor of T cell immunoglobulin and mucin domain-containing protein 3 (TIM-3).
  arm group label: TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules
  intervention type: Drug
  intervention name: Anlotinib Hydrochloride Capsules
  description: Anlotinib hydrochloride is a muti-target tyrosine kinase inhibitor.
  arm group label: TQB2618 injection +Penpulimab injection+ Anlotinib Hydrochloride Capsules
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Qiang Xia, Doctor
  phone: +86 13661889035
  email: Xiaqiang@medmail.com.cn
  last name: Hao Feng, Doctor
  phone: +86 15000901110
  email: Fenghao@renji.com
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Hepatocellular