<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/NCT03013101</url>
  </required_header>
  <id_info>
    <org_study_id>Junshi-JS001-BJZL-II</org_study_id>
    <nct_id>NCT03013101</nct_id>
  </id_info>
  <brief_title>Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Patients With Locally Advanced or Metastatic Melanoma</brief_title>
  <official_title>A Phase II, Open, Multi-center and Single Arm Study Investigating Safety and Efficacy of Recombinant Humanized Anti-PD-1 mAb for Injection in Patients With Locally Advanced or Metastatic Melanoma and Standard Treatment Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Junshi Bioscience Co., Ltd.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Junshi Bioscience Co., Ltd.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a multi-center, open-label, phase 2 study evaluating the humanized anti-PD-1 antibody&#xD;
      JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who have&#xD;
      failed in routine systemic treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multiple-center, open-label, phase 2 study evaluating the humanized anti-PD-1&#xD;
      antibody JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who&#xD;
      have failed in previous routine systemic treatment. Patients are injected with JS001 with&#xD;
      3mg/kg every 2 weeks until disease progresses or unacceptable toxicity occurs. Response&#xD;
      assessment is conducted by every 8 weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">December 28, 2016</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Actual">September 16, 2018</primary_completion_date>
  <phase>Phase 2</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>Objective response rate (ORR) by RECIST 1.1 and irRECIST Objective response rate (ORR) by RECIST 1.1 and irRECIST</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) by RECIST1.1 and irRECIST</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival (PFS) by RECIST1.1 and irRECIST</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of anti-PD-1 monoclonal antibody</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with treatment-related adverse events as assessed by CTCAE v4.0</measure>
    <time_frame>1.5 years</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Correlation analysis of PD-L1 expression of tumor by Immunohistochemistry and ORR</measure>
    <time_frame>3 years</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">128</enrollment>
  <condition>Advanced Melanoma</condition>
  <condition>Metastatic Melanoma</condition>
  <arm_group>
    <arm_group_label>humanized anti-PD-1monoclonal antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>humanized anti-PD-1 monoclonal antibody toripalimab</intervention_name>
    <description>humanized anti-PD-1 monoclonal antibody (JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.</description>
    <arm_group_label>humanized anti-PD-1monoclonal antibody</arm_group_label>
    <other_name>JS001, TAB001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and Female aged 18 and older are eligible;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1;&#xD;
&#xD;
          -  Histologic diagnosis of locally advanced or metastatic melanoma, while ocular melanoma&#xD;
             is excluded, and the overall rate of mucousal melanoma is no more than 25%.&#xD;
&#xD;
          -  Have failed at least 1 prior routine regimen for advanced disease.&#xD;
&#xD;
          -  Providing with tumor specimen (for testing the expression of PD -L1 and the&#xD;
             infiltrating lymphocytes);&#xD;
&#xD;
          -  documentary evidence of BRAF mutation status;&#xD;
&#xD;
          -  At least 1 measurable lesion (only 1 measurable lymph node lesion is excluded)&#xD;
             (routine CT scan &gt;=20mm, spiral CT scan &gt;=10mm, no prior radiation to measurable&#xD;
             lesions) Predicted survival &gt;=3 months;&#xD;
&#xD;
          -  Brain or meningeal metastases must be disposed with surgery or radiation, and be&#xD;
             stable clinically for at least 3 months (prior systemic steroids was allowed, but&#xD;
             concurrent administration of systemic steroids with the study drug is excluded).&#xD;
&#xD;
          -  Screening laboratory values must meet the following criteria（within past 14 days）:&#xD;
&#xD;
        hemoglobin ≥ 9.0 g/dL; neutrophils ≥ 1500 cells/ µL; platelets ≥ 100 x 10^3/ µL; total&#xD;
        bilirubin ≤ 1.5 x upper limit of normal (ULN); aspartic transaminase (AST) and alanine&#xD;
        transaminase (ALT) ≤ 2.5 x ULN without, and ≤ 5 x ULN with hepatic metastasis; serum&#xD;
        creatinine ≤1╳ULN，creatinine clearance &gt;50ml/min (Cockcroft-Gault equation) PT/INR,&#xD;
        aPTT≤1.5 x ULN;&#xD;
&#xD;
          -  Without systemic steroids within past 4 weeks&#xD;
&#xD;
          -  Males or female of childbearing potential must: agree to use using a reliable form of&#xD;
             contraception (eg, oral contraceptives, intrauterine device, control sex desire,&#xD;
             double barrier method of condom and spermicidal) during the treatment period and for&#xD;
             at least 12 months after the last dose of study drug.&#xD;
&#xD;
          -  Must have read, understood, and provided written informed consent voluntarily. Willing&#xD;
             to adhere to the study visit schedule and the prohibitions and restrictions specified&#xD;
             in this protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody;&#xD;
&#xD;
          -  Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Ab or its components.&#xD;
&#xD;
          -  Prior treatment with mAb within past 4 weeks.&#xD;
&#xD;
          -  Prior antitumor therapy (including corticosteroids and immunotherapy) or participation&#xD;
             in other clinical trials within past 4 weeks, or have not recovered from toxicities&#xD;
             since the last treatment;&#xD;
&#xD;
          -  Pregnant or nursing;&#xD;
&#xD;
          -  Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (&gt;500IU/ml)&#xD;
&#xD;
          -  History with tuberculosis;&#xD;
&#xD;
          -  Patients with any active autoimmune disease or a documented history of autoimmune&#xD;
             disease, or history of syndrome that required systemic steroids or immunosuppressive&#xD;
             medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis,&#xD;
             hyperthyroidism or hypothyroidism.&#xD;
&#xD;
          -  Severe, uncontrolled medical condition that would affect patients' compliance or&#xD;
             obscure the interpretation of toxicity determination or adverse events, including&#xD;
             active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure &gt;&#xD;
             class II NYHA, heart block &gt;II grade, myocardial infarction, unstable arrhythmia or&#xD;
             unstable angina within past 6 months, cerebral infarction within past 3 months) or&#xD;
             pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or&#xD;
             symptomatic bronchospasm).&#xD;
&#xD;
          -  Evidence with active CNS disease.&#xD;
&#xD;
          -  meningeal carcinomatosis;&#xD;
&#xD;
          -  Prior treatment with bone marrow stimulating factors，such as CSF (colony stimulating&#xD;
             factor), EPO (erythropoietin), within past 2 weeks&#xD;
&#xD;
          -  Prior live vaccine therapy within past 4 weeks.&#xD;
&#xD;
          -  Prior major surgery within past 4 weeks (diagnostic surgery excluded).&#xD;
&#xD;
          -  Psychiatric medicines abuse without withdrawal, or history of psychiatric illness.&#xD;
&#xD;
          -  Prior malignancy active within the previous 5 years except for locally curable cancers&#xD;
             that have been apparently cured, such as basal cell skin cancer or carcinoma in situ&#xD;
             of the cervix.&#xD;
&#xD;
          -  Underlying medical condition that, in the Investigator's opinion, would increase the&#xD;
             risks of study drug administration or obscure the interpretation of toxicity&#xD;
             determination or adverse events.&#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>Jun Guo, PhD, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100142</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sun Yat-sen University Cancer center</name>
      <address>
        <city>Guangzhou</city>
        <state>Guangdong</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wuhan Union Hospital</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The 81st Hospital of Chinese People's Liberation Army</name>
      <address>
        <city>Nanjing</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The First Hospital of Jilin University</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yunnan Cancer Hospital</name>
      <address>
        <city>Kunming</city>
        <state>Yunnan</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.</citation>
    <PMID>22658127</PMID>
  </reference>
  <reference>
    <citation>Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.</citation>
    <PMID>24590637</PMID>
  </reference>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>September 28, 2020</last_update_submitted>
  <last_update_submitted_qc>September 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 30, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>anti-PD-1 monoclonal antibody</keyword>
  <keyword>advanced</keyword>
  <keyword>metastatic</keyword>
  <keyword>melanoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Antibodies</mesh_term>
    <mesh_term>Antibodies, Monoclonal</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03013101
org study id: Junshi-JS001-BJZL-II
nct id: NCT03013101
lead sponsor: 
has dmc: Yes
This is a multi-center, open-label, phase 2 study evaluating the humanized anti-PD-1 antibody
      JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who have
      failed in routine systemic treatment.
This is a multiple-center, open-label, phase 2 study evaluating the humanized anti-PD-1
      antibody JS001, as a monotherapy in patients with locally advanced or metastatic melanoma who
      have failed in previous routine systemic treatment. Patients are injected with JS001 with
      3mg/kg every 2 weeks until disease progresses or unacceptable toxicity occurs. Response
      assessment is conducted by every 8 weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Objective response rate (ORR) by RECIST 1.1 and irRECIST Objective response rate (ORR) by RECIST 1.1 and irRECIST
time frame: 3 years
measure: Duration of response (DOR) by RECIST1.1 and irRECIST
time frame: 3 years
measure: Progression free survival (PFS) by RECIST1.1 and irRECIST
time frame: 3 years
measure: Overall survival (OS)
time frame: 3 years
measure: Immunogenicity of anti-PD-1 monoclonal antibody
time frame: 1.5 years
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
time frame: 1.5 years
measure: Correlation analysis of PD-L1 expression of tumor by Immunohistochemistry and ORR
time frame: 3 years
arm group label: humanized anti-PD-1monoclonal antibody
arm group type: Experimental
description: humanized anti-PD-1 monoclonal antibody is to be injected intravenously 3mg/kg Q2w until disease progresses or unacceptable tolerability occurs
intervention type: Biological
intervention name: humanized anti-PD-1 monoclonal antibody toripalimab
description: humanized anti-PD-1 monoclonal antibody (JS001) is a programmed death-1 (PD-1) immune checkpoint inhibitor antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2, resulting in the activation of lymphocytes and elimination of malignancy theoretically.
arm group label: humanized anti-PD-1monoclonal antibody
other name: JS001, TAB001
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jun Guo, PhD, MD
role: Principal Investigator
affiliation: Peking University Cancer Hospital & Institute
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
citation: Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, Powderly JD, Carvajal RD, Sosman JA, Atkins MB, Leming PD, Spigel DR, Antonia SJ, Horn L, Drake CG, Pardoll DM, Chen L, Sharfman WH, Anders RA, Taube JM, McMiller TL, Xu H, Korman AJ, Jure-Kunkel M, Agrawal S, McDonald D, Kollia GD, Gupta A, Wigginton JM, Sznol M. Safety, activity, and immune correlates of anti-PD-1 antibody in cancer. N Engl J Med. 2012 Jun 28;366(26):2443-54. doi: 10.1056/NEJMoa1200690. Epub 2012 Jun 2.
PMID: 22658127
citation: Topalian SL, Sznol M, McDermott DF, Kluger HM, Carvajal RD, Sharfman WH, Brahmer JR, Lawrence DP, Atkins MB, Powderly JD, Leming PD, Lipson EJ, Puzanov I, Smith DC, Taube JM, Wigginton JM, Kollia GD, Gupta A, Pardoll DM, Sosman JA, Hodi FS. Survival, durable tumor remission, and long-term safety in patients with advanced melanoma receiving nivolumab. J Clin Oncol. 2014 Apr 1;32(10):1020-30. doi: 10.1200/JCO.2013.53.0105. Epub 2014 Mar 3.
PMID: 24590637
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Antibodies
mesh term: Antibodies, Monoclonal
sharing ipd: Undecided