<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/NCT03757936</url>
  </required_header>
  <id_info>
    <org_study_id>HLX10HLX04-001</org_study_id>
    <nct_id>NCT03757936</nct_id>
  </id_info>
  <brief_title>A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Anti-PD-1 Antibody (HLX10) in Combination With Avastin Biosimilar (HLX04) in Patients With Advanced Solid Tumors</brief_title>
  <official_title>A Phase I Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection (HLX10) in Combination With Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection (HLX04) in Patients With Advanced Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Henlius Biotech</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Henlius Biotech</source>
  <oversight_info>
    <has_dmc>Yes</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 single-center, open-label, dose-escalation Phase I clinical trial to evaluate the&#xD;
      safety and the tolerability of HLX10-HLX04 combination therapy in patients with advanced&#xD;
      solid tumors after failure of standard of care.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 27, 2018</start_date>
  <completion_date type="Anticipated">December 27, 2020</completion_date>
  <primary_completion_date type="Anticipated">September 27, 2019</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>Maximum Tolerated Dose (MTD) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>28 days</time_frame>
    <description>The MTD is the dose with toxicity rate (estimated by isotonic regression) most approximate to the target one (30%).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose Limiting Toxicity (DLT) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>28 days</time_frame>
    <description>DLT is defined as the occurrence of the following adverse events (unless judged by the investigator to be definitely unrelated to HLX04 or HLX10) within Cycle 1 (i.e., from Cycle 1 Day 1 to Cycle 1 Day 28)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>Peak Plasma Concentration (Cmax) for single dose and multiple doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>Area under the plasma concentration versus time curve (AUC) for single dose and multiple doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>ORR determined by RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>DCR determined by RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>DOR determined by RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>PFS determined by RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS) of HLX04 plus HLX10 in patients with advanced solid tumors</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>OS determined by RECIST criteria</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity</measure>
    <time_frame>Day 1 of treatment up to 2 years</time_frame>
    <description>Anti-drug Antibody (ADA) Testing</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Solid Tumor</condition>
  <arm_group>
    <arm_group_label>HLX04+HLX10</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>HLX10, at three dose levels (1, 3, 10 mg/kg), to be intravenously injected once every two weeks; HLX04, at a fixed dose of 5 mg/kg, intravenously injected once every two weeks; Study drugs given in combination for up to 2 years or until the disease gets worse, whichever comes first.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HLX04</intervention_name>
    <description>Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection</description>
    <arm_group_label>HLX04+HLX10</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HLX10</intervention_name>
    <description>Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection</description>
    <arm_group_label>HLX04+HLX10</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥18 years, male or female&#xD;
&#xD;
          2. Patient with histologically or cytologically confirmed advanced malignant solid tumors&#xD;
             who have failed standard of care, or has no standard-of-care therapy or are not&#xD;
             suitable for standard of care at the present stage;&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1；&#xD;
&#xD;
          4. Life expectancy greater than 3 months;&#xD;
&#xD;
          5. Patient must have at least one measurable tumor lesion as defined by RECIST v1.1; the&#xD;
             lesion concerned must not be a bone metastasis if only one target lesion is present;&#xD;
&#xD;
          6. Has adequate organ functions;&#xD;
&#xD;
          7. If the subject is a patient with hepatocellular carcinoma, Child-Pugh classification&#xD;
             must be A.&#xD;
&#xD;
          8. A qualified patient (male or female) of childbearing potential must agree to use&#xD;
             reliable contraceptive methods (hormonal, or barrier method or abstinence) for the&#xD;
             course of the study and through at least 6 months after the last dose; a female&#xD;
             patient of childbearing potential must have negative blood pregnancy test within 7&#xD;
             days prior to enrollment;&#xD;
&#xD;
          9. The subject must give his/her informed consent to this study prior to the trial, and&#xD;
             voluntarily sign a written informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histopathological confirmed head and neck cancer or squamous-cell lung cancer, or&#xD;
             bleeding tendency in the tumor lesion judged by the investigator;&#xD;
&#xD;
          2. Has received antitumor therapy like radiotherapy, chemotherapy, targeted therapy,&#xD;
             endocrinal therapy or immunotherapy, or other clinical study drug therapy within 4&#xD;
             months prior to the initial drug administration;&#xD;
&#xD;
          3. Has received a surgical operation on major viscera or experienced apparent trauma&#xD;
             within 4 weeks from the initial drug administration, or experienced subcutaneous&#xD;
             venous access device implantation within 7 days;&#xD;
&#xD;
          4. The adverse reactions which occurred in the previous antitumor treatment were not&#xD;
             recovered to ≤ grade 1 based on CTCAE 4.03 assessment (except for hair loss);&#xD;
&#xD;
          5. Evidences of metastatic lesion in the patient's central nervous system;&#xD;
&#xD;
          6. Previously experienced ≥ grade 3 immune-related adverse event during immunotherapy;&#xD;
&#xD;
          7. Active, or history of autoimmune disease which may relapse (for example, systemic&#xD;
             lupus erythematosus, rheumatoid arthritis, vasculitis, etc.);&#xD;
&#xD;
          8. Currently having or have had interstitial lung disease;&#xD;
&#xD;
          9. Uncontrollable active infection(s);&#xD;
&#xD;
         10. History of immunodeficiency, including HIV antibody positive;&#xD;
&#xD;
         11. Known active hepatitis B; or hepatitis C virus infections;&#xD;
&#xD;
         12. Has bleeding tendency;&#xD;
&#xD;
         13. History of severe cardiovascular diseases;&#xD;
&#xD;
         14. Known gastrointestinal diseases as follows:&#xD;
&#xD;
             Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months&#xD;
             before signing the informed consent; History of poorly controlled or recurrent&#xD;
             inflammatory bowel disease; Active peptic ulcers, or &gt; moderate esophageal varices;&#xD;
&#xD;
         15. Known hypersensitivity to Bevacizumab, or other anti-PD-1, anti-PD-L1 monoclonal&#xD;
             antibody agents;&#xD;
&#xD;
         16. Pregnant or breastfeeding female.&#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>Joanne Wang</last_name>
    <phone>+86-021-33395800-6024</phone>
    <email>Joanne_wang@henlius.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jin Li, MD</last_name>
      <email>lijin@csco.org.cn</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>November 19, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <last_update_submitted>May 22, 2019</last_update_submitted>
  <last_update_submitted_qc>May 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 23, 2019</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>
  <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/NCT03757936
org study id: HLX10HLX04-001
nct id: NCT03757936
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a single-center, open-label, dose-escalation Phase I clinical trial to evaluate the
      safety and the tolerability of HLX10-HLX04 combination therapy in patients with advanced
      solid tumors after failure of standard of care.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: 28 days
description: The MTD is the dose with toxicity rate (estimated by isotonic regression) most approximate to the target one (30%).
measure: Dose Limiting Toxicity (DLT) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: 28 days
description: DLT is defined as the occurrence of the following adverse events (unless judged by the investigator to be definitely unrelated to HLX04 or HLX10) within Cycle 1 (i.e., from Cycle 1 Day 1 to Cycle 1 Day 28)
measure: PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: Peak Plasma Concentration (Cmax) for single dose and multiple doses
measure: PK parameters of the HLX04 plus HLX10 therapy in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: Area under the plasma concentration versus time curve (AUC) for single dose and multiple doses
measure: Objective Response Rate (ORR) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: ORR determined by RECIST criteria
measure: Disease Control Rate (DCR) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: DCR determined by RECIST criteria
measure: Duration of Response (DOR) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: DOR determined by RECIST criteria
measure: Progression-Free Survival (PFS) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: PFS determined by RECIST criteria
measure: Overall Survival (OS) of HLX04 plus HLX10 in patients with advanced solid tumors
time frame: Day 1 of treatment up to 2 years
description: OS determined by RECIST criteria
measure: Immunogenicity
time frame: Day 1 of treatment up to 2 years
description: Anti-drug Antibody (ADA) Testing
arm group label: HLX04+HLX10
arm group type: Experimental
description: HLX10, at three dose levels (1, 3, 10 mg/kg), to be intravenously injected once every two weeks; HLX04, at a fixed dose of 5 mg/kg, intravenously injected once every two weeks; Study drugs given in combination for up to 2 years or until the disease gets worse, whichever comes first.
intervention type: Drug
intervention name: HLX04
description: Recombinant Anti-VEGF Humanized Monoclonal Antibody Injection
arm group label: HLX04+HLX10
intervention type: Drug
intervention name: HLX10
description: Recombinant Anti-PD-1 Humanized Monoclonal Antibody Injection
arm group label: HLX04+HLX10
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Joanne Wang
phone: +86-021-33395800-6024
email: Joanne_wang@henlius.com
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No