<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/NCT03301688</url>
  </required_header>
  <id_info>
    <org_study_id>Junshi-JS001-012</org_study_id>
    <nct_id>NCT03301688</nct_id>
  </id_info>
  <brief_title>The Pharmacokinetics and Safety of Single-dose and Parallel Comparisons in Patients With NSCLC Treated With JS001</brief_title>
  <official_title>A Similar Phase I Study on the Pharmacokinetics and Safety of Single-dose and Parallel Comparisons in Patients With Advanced NSCLC Treated With Recombinant Humanized Anti-PD-1 Monoclonal Antibody (JS001) Before and After Process Change</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>
    <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 was designed to evaluate the similarity of single-dose and parallel comparisons of&#xD;
      recombinant humanized anti-PD-1 monoclonal antibody injections before and after process&#xD;
      changes. It is designed to be a single-center, open and parallel controlled phase I study.&#xD;
      Patients with advanced NSCLC will be enrolled.&#xD;
&#xD;
      After determining that the patient is qualified, the patient will be assigned to a batch of&#xD;
      drug use in the order in which they are selected. The dosage of drug was set at 3 mg / kg.&#xD;
      Planned to recruit subjects each 12 patients (24 cases) to participate in this study, taking&#xD;
      into account a 20% dropout rate, so that the total of 15 patients (30 patients) subjects in&#xD;
      each group in this study.&#xD;
&#xD;
      This study was divided into study phase (single-dose period) and follow-up stage&#xD;
      (multiple-dose period).Each subject first conducted a single dose safety and pharmacokinetics&#xD;
      (PK) study.If the subject did not develop adverse events that had significant clinical&#xD;
      significance as suggested by the investigators within 28 days of the single dose and&#xD;
      continued reorganization of the humanized anti-PD-1 monoclonal antibody injection to benefit&#xD;
      the patient , and with the agreement of subjects, the subject will enter the follow-up phase&#xD;
      (multiple-dose period). The same dose of recombinant humanized anti-PD-1 monoclonal antibody&#xD;
      injection was administered once every 2 weeks and 4 consecutive cycles of treatment for one&#xD;
      cycle of continuous period.Until the patient has developed tumor progression or an&#xD;
      untolerated toxic side effect, the patient voluntarily exits the study or believes that the&#xD;
      situation is not suitable for continuing treatment. There are follow-up of 90 days after&#xD;
      treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 18, 2017</start_date>
  <completion_date type="Actual">December 15, 2019</completion_date>
  <primary_completion_date type="Actual">September 15, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>6 months</time_frame>
    <description>Objective Response Rate (ORR) by irRC and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>6 months</time_frame>
    <description>Duration of response (DOR) by irRC and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate (DCR)</measure>
    <time_frame>6 months</time_frame>
    <description>Disease control rate (DCR) by irRC and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>6 months</time_frame>
    <description>Progression Free Survival (PFS) by irRC and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>6 months</time_frame>
    <description>Overall Survival (OS) by irRC and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>6 months</time_frame>
    <description>Time to response (TTR) by irRC and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb)</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Average Plasma Concentration (Cav) of steady state after multiple dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>degree of fluctuation (DF) of steady state after multiple dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb</measure>
    <time_frame>6 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>A group (JS001 20161002)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects of A group will use 3 mg/kg doses every 2 weeks.Drug batch number is 20161002.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>B group (JS001 20161108)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The subjects of B group will use 3 mg/kg doses every 2 weeks.Drug batch number is 20161108.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Toripalimab</intervention_name>
    <description>To compare the different drug batch number with different process</description>
    <arm_group_label>A group (JS001 20161002)</arm_group_label>
    <arm_group_label>B group (JS001 20161108)</arm_group_label>
    <other_name>JS001, TAB001</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Male and Female aged 18 to 70 years are eligible;&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1&#xD;
&#xD;
          -  Histologic diagnosis of NSCLS. Have failed at least 1 prior routine regimen for&#xD;
             metastatic disease, or failed to tolerate the toxicity, or lack of any routine&#xD;
             regimens.&#xD;
&#xD;
          -  Providing with tumor specimen (for testing the expression of PD -L1 and the&#xD;
             infiltrating lymphocytes);&#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;=6 months;&#xD;
&#xD;
          -  Brain or meningeal metastases must be disposed with surgery or radiation, and be&#xD;
             stable clinically for at least 8 weeks (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)&#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. -&#xD;
             Willing to adhere to the study visit schedule and the prohibitions and restrictions&#xD;
             specified in this protocol.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Hypersensitivity to recombinant humanized anti-PD-1 monoclonal Ab or its components.&#xD;
&#xD;
          -  Prior treatment with mAb within past 3 months (locally administration excluded)&#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;
          -  Abnormal Blood coagulation&#xD;
&#xD;
          -  Positive tests for HIV, HCV, HBsAg or HBcAb with positive test for HBV DNA (&gt;500IU/ml)&#xD;
&#xD;
          -  History with pulmonary 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;
          -  Prior treatment with bone marrow stimulating factors，such as CSF (colony stimulating&#xD;
             factor), EPO (erythropoietin), within past 1 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>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jie Wang, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Hospital Chinese Academy of Medical Science</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cancer Hospital Chinese Academy of Medical Science</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 29, 2017</study_first_submitted>
  <study_first_submitted_qc>September 29, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 4, 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>PD-1 antibody</keyword>
  <keyword>phase 1 trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_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/NCT03301688
org study id: Junshi-JS001-012
nct id: NCT03301688
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study was designed to evaluate the similarity of single-dose and parallel comparisons of
      recombinant humanized anti-PD-1 monoclonal antibody injections before and after process
      changes. It is designed to be a single-center, open and parallel controlled phase I study.
      Patients with advanced NSCLC will be enrolled.

      After determining that the patient is qualified, the patient will be assigned to a batch of
      drug use in the order in which they are selected. The dosage of drug was set at 3 mg / kg.
      Planned to recruit subjects each 12 patients (24 cases) to participate in this study, taking
      into account a 20% dropout rate, so that the total of 15 patients (30 patients) subjects in
      each group in this study.

      This study was divided into study phase (single-dose period) and follow-up stage
      (multiple-dose period).Each subject first conducted a single dose safety and pharmacokinetics
      (PK) study.If the subject did not develop adverse events that had significant clinical
      significance as suggested by the investigators within 28 days of the single dose and
      continued reorganization of the humanized anti-PD-1 monoclonal antibody injection to benefit
      the patient , and with the agreement of subjects, the subject will enter the follow-up phase
      (multiple-dose period). The same dose of recombinant humanized anti-PD-1 monoclonal antibody
      injection was administered once every 2 weeks and 4 consecutive cycles of treatment for one
      cycle of continuous period.Until the patient has developed tumor progression or an
      untolerated toxic side effect, the patient voluntarily exits the study or believes that the
      situation is not suitable for continuing treatment. There are follow-up of 90 days after
      treatment.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Area Under the Curve (AUC) after single dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: Objective response rate (ORR)
time frame: 6 months
description: Objective Response Rate (ORR) by irRC and RECIST 1.1
measure: Duration of response (DOR)
time frame: 6 months
description: Duration of response (DOR) by irRC and RECIST 1.1
measure: Disease control rate (DCR)
time frame: 6 months
description: Disease control rate (DCR) by irRC and RECIST 1.1
measure: Progression Free Survival (PFS)
time frame: 6 months
description: Progression Free Survival (PFS) by irRC and RECIST 1.1
measure: Overall Survival (OS)
time frame: 6 months
description: Overall Survival (OS) by irRC and RECIST 1.1
measure: Time to response (TTR)
time frame: 6 months
description: Time to response (TTR) by irRC and RECIST 1.1
measure: Maximum Plasma Concentration (Cmax) after single dose injection of Anti-PD-1 Monoclonal Antibody (mAb)
time frame: 6 months
measure: Peak Time (Tmax) after single dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: t1/2 after single dose injection of Recombinant Humanized Anti-PD-1 mAb
time frame: 6 months
measure: Plasma clearance (CL) after single dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: Apparent volume of distribution (V) after single dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: Minimum Plasma Concentration (Cmin) of steady state after multiple dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: Average Plasma Concentration (Cav) of steady state after multiple dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: degree of fluctuation (DF) of steady state after multiple dose injection of Anti-PD-1 mAb
time frame: 6 months
measure: Apparent volume of distribution of steady state (Vss) after multiple dose injection of Anti-PD-1 mAb
time frame: 6 months
arm group label: A group (JS001 20161002)
arm group type: Experimental
description: The subjects of A group will use 3 mg/kg doses every 2 weeks.Drug batch number is 20161002.
arm group label: B group (JS001 20161108)
arm group type: Experimental
description: The subjects of B group will use 3 mg/kg doses every 2 weeks.Drug batch number is 20161108.
intervention type: Biological
intervention name: Toripalimab
description: To compare the different drug batch number with different process
arm group label: A group (JS001 20161002)
arm group label: B group (JS001 20161108)
other name: JS001, TAB001
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jie Wang, MD, PhD
role: Principal Investigator
affiliation: Cancer Hospital Chinese Academy of Medical Science
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: Undecided