<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/NCT03251313</url>
  </required_header>
  <id_info>
    <org_study_id>Fudan-P1-201701</org_study_id>
    <nct_id>NCT03251313</nct_id>
  </id_info>
  <brief_title>PD-1(Programmed Death-1) Antibody +GP as First Line Treatment for Triple Negative Breast Cancer(TNBC) Patients</brief_title>
  <official_title>Recombinant Humanized PD-1 Monoclonal Antibody (JS001) Combined With Gemcitabine and Cisplatin (GP) as First Line Treatment for Triple Negative Breast Cancer patients-a Phase 1 Clinical Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Fudan University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Fudan University</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase I dose escalation trial to assess dose-limiting toxicity (DLT) and MTD of&#xD;
      JS001+GP in advanced/metastatic TNBC patients, and to determine the recommended Phase II dose&#xD;
      and the best combination regimen.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      There will be 3 stages in this trial. Stage 1 is the dose escalation stage. JS001 will be&#xD;
      tested in combination with GP in 3 dose levels.&#xD;
&#xD;
      Level 1: 120mg Level 2: 240mg Level 3: 480mg Patients will receive JS001+GP for 6 cycles and&#xD;
      JS001 maintenance therapy for up to approximately 2 years.&#xD;
&#xD;
      JS001 will be given on d1 every 3 weeks with GP and every 2 weeks in maintenance therapy.&#xD;
&#xD;
      The first group of participants will receive the lowest dose level of JS001 at 120mg. Each&#xD;
      new group will receive a higher dose of JS001 than the group before it until 480mg.&#xD;
&#xD;
      Stage 2 is the dose expansion stage. Dose expansion will be carried out to expand to 12&#xD;
      patients in the highest dose level at which the patient can tolerate well. This dose will&#xD;
      also be recommended as phase 2 dose(RP2D).&#xD;
&#xD;
      Stage 3 is the sequential treatment stage. Patients receive 6 cycles of GP without JS001 and&#xD;
      then receive JS001 maintenance therapy for up to approximately 2 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">May 15, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 30, 2022</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>Maximum Tolerated Dose (MTD) of JS001 when combined with GP</measure>
    <time_frame>3 weeks</time_frame>
    <description>If 1/6 patients has grade 3 or higher toxicity then escalation proceeds, if 2/6 has grade 3 or greater toxicity then this is declared MTD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peak Plasma Concentration (Cmax)</measure>
    <time_frame>85 days</time_frame>
    <description>Cmax of JS001</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the plasma concentration versus time curve (AUC)</measure>
    <time_frame>85 days</time_frame>
    <description>AUC of JS001</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>other pharmacokinetics(PK) characteristics of JS001+GP</measure>
    <time_frame>85 days</time_frame>
    <description>half life of JS001</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>85 days</time_frame>
    <description>Incidence of Adverse Events that need to be treated immediately</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of Severe Adverse Events</measure>
    <time_frame>85 days</time_frame>
    <description>Incidence of Adverse Events that cause hospitalization, inability, death, etc</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>objective response rate of JS001+GP</measure>
    <time_frame>1 year</time_frame>
    <description>objective response rate(%) is the sum of CR(complete remission) rate and PR(partial remission) rate</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>disease control rate of JS001+GP</measure>
    <time_frame>1 year</time_frame>
    <description>disease control rate(%) is the sum of CR rate and PR rate and SD(stable disease) rate for more than 6 weeks</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>duration of regression of JS001+GP</measure>
    <time_frame>1 year</time_frame>
    <description>duration of regression(months) is the time interval from randomization to disease progression</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>time to regression of JS001+GP</measure>
    <time_frame>1 year</time_frame>
    <description>time to regression(months) is the time interval from randomization to disease regressin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>progression free survival of JS001+GP</measure>
    <time_frame>1 year</time_frame>
    <description>progression free survival(months) is the time interval from randomization to disease progression or death from any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall survival of JS001+GP</measure>
    <time_frame>1 year</time_frame>
    <description>overall survival(months) is the time interval between randomization and death from any reason</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>best combination regimen</measure>
    <time_frame>1 year</time_frame>
    <description>Is JS001 combined with GP or GP followed by JS001 better in safety (incidence of grade 3-4 toxicity) and efficacy(Response Rate and PFS)</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Triple Negative Breast Cancer</condition>
  <arm_group>
    <arm_group_label>JS001 120mg+GP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Level 1: JS001 120mg +GP q3w,*6 cycles, then JS001 120mg q3w for maintenance therapy for up to approximately 2 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>JS001 240mg+GP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Level 2: JS001 240mg +GP q3w,*6 cycles, then JS001 240mg q3w for maintenance therapy for up to approximately 2 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>JS001 480mg +GP</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Level 3: JS001 480mg+GP q3w,*6 cycles, then JS001 480mg q3w for maintenance therapy for up to approximately 2 years.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GP followed by JS001</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>sequential treatment: Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years. JS001 will be given at RP2D.</description>
  </arm_group>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>JS001 120mg+GP</intervention_name>
    <description>In this arm, JS001 120mg will be given at d1; Gem 1000mg/m2 d2,9; DDP(cisplatin) 75mg/m2 d2</description>
    <arm_group_label>JS001 120mg+GP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>JS001 240mg+GP</intervention_name>
    <description>In this arm, JS001 240mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2</description>
    <arm_group_label>JS001 240mg+GP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>JS001 480mg+GP</intervention_name>
    <description>In this arm, JS001 480mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2</description>
    <arm_group_label>JS001 480mg +GP</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Combination Product</intervention_type>
    <intervention_name>GP followed by JS001</intervention_name>
    <description>In this arm,Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years. JS001 will be given at RP2D.</description>
    <arm_group_label>GP followed by JS001</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically confirmed relapsed or metastatic triple negative breast cancer&#xD;
&#xD;
          -  Subjects must have normal organ and marrow function as defined below:&#xD;
&#xD;
          -  White blood cell ≥ 3,000/μL, Absolute neutrophil count ≥ 1,500/μL, Hemoglobin ≥ 9.0&#xD;
             g/dl, Platelet count ≥ 100,000/μL&#xD;
&#xD;
          -  Total bilirubin ≤1.25 X institutional upper limit of normal , aspartate&#xD;
             aminotransferase(AST) ≤ 2.5 X institutional upper limit of normal, alanine&#xD;
             transaminase(ALT) ≤ 2.5 X institutional upper limit of normal (For patients with liver&#xD;
             metastasis, Total bilirubin ≤1.5 X institutional upper limit of normal , AST ≤5 X&#xD;
             institutional upper limit of normal, ALT ≤5 X institutional upper limit of normal)&#xD;
&#xD;
          -  Serum creatinine within normal institutional limits&#xD;
&#xD;
          -  thyroid-stimulating hormone ,FT3(free triiodothyronine),FT4(Free thyroid hormone)&#xD;
             within 0.9 X institutional lower limit of normal to 1.1 X institutional upper limit of&#xD;
             normal (Except for patients who had thyroid ectomy)&#xD;
&#xD;
          -  Basically normal EKG and left ventricular ejection fraction(LVEF)&gt;50%&#xD;
&#xD;
          -  Life expectancy of 6 months or more&#xD;
&#xD;
          -  Performance Status 0-1&#xD;
&#xD;
          -  Subjects must have at least one measurable disease per RECIST v1.1&#xD;
&#xD;
          -  Weight more than 45 Kilogram&#xD;
&#xD;
          -  Subjects must have not received chemotherapy in metastatic setting, subjects relapsed&#xD;
             6 months after the completion of adjuvant therapy are eligible&#xD;
&#xD;
          -  Subjects must be willing to supply fresh or archive tumor tissue for research purposes&#xD;
&#xD;
          -  Subjects must have stopped receiving any anti-cancer treatment (including&#xD;
             chemotherapy, curative radiotherapy, and surgery or targeting therapy) for at least 4&#xD;
             weeks.&#xD;
&#xD;
          -  Subjects must have stopped receiving systemic immunosuppressive agents for at least 2&#xD;
             weeks.&#xD;
&#xD;
          -  Subjects must have the ability to understand and the willingness to sign a written&#xD;
             informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with radiographically stable treated brain metastases are eligible but must&#xD;
             not have been on steroid therapy for at least 4 weeks&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to Gemcitabine, cisplatin or JS001&#xD;
&#xD;
          -  Patients who have adjuvant chemotherapy and relapsed within 6 months.&#xD;
&#xD;
          -  Pregnant or breastfeeding women are excluded from this study&#xD;
&#xD;
          -  Patients with HIV infection, patients with positive HbsAg or HCV(hepatitis C&#xD;
             virus)-RNA&#xD;
&#xD;
          -  Patients with chronic autoimmune disease&#xD;
&#xD;
          -  Patients with prior therapy with antibodies that modulate T-cell function (e.g.,&#xD;
             anti-PD-1, anti-PD-L1, anti-CTLA-4(Cytotoxic T-lymphocyte-associated protein 4))&#xD;
&#xD;
          -  Patients with evidence of active, non-infectious pneumonia&#xD;
&#xD;
          -  Patients with a history of tuberculosis&#xD;
&#xD;
          -  Patients active infection requiring intravenous systemic therapy&#xD;
&#xD;
          -  Severe cardiovascular disease&#xD;
&#xD;
          -  Severe gastrointestinal dysfunction (bleeding, infection, obstruction or ≥ grade 1&#xD;
             diarrhea)&#xD;
&#xD;
          -  Patients with severe coagulation dysfunction or bleeding tendency, patients who are&#xD;
             receiving thrombolysis or anticoagulation therapy&#xD;
&#xD;
          -  Subjects with uncontrolled intercurrent illness including, but not limited to ongoing&#xD;
             or active infection, symptomatic congestive heart failure, unstable angina pectoris,&#xD;
             cardiac arrhythmia, severe hyper blood pressure, severe diabetes or severe thyroid&#xD;
             disease that would limit compliance with study requirements&#xD;
&#xD;
          -  Patients with known psychiatric disorders that would interfere with cooperation with&#xD;
             requirements of the trial&#xD;
&#xD;
          -  Patients who have received a vaccine within 4 weeks prior to the first dose of JS001&#xD;
&#xD;
          -  Patients with a known additional malignancy that is progressing or requires active&#xD;
             treatment (within the last 5 years). Exceptions: basal cell carcinoma of the skin,&#xD;
             squamous cell carcinoma of the skin or in situ cancers that has undergone potentially&#xD;
             curative therapy&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xichun Hu, MD&amp; PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Fudan University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Fudan University Shanghai Cancer Center</name>
      <address>
        <city>Shanghai</city>
        <zip>200032</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>June 7, 2017</study_first_submitted>
  <study_first_submitted_qc>August 12, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 16, 2017</study_first_posted>
  <last_update_submitted>April 19, 2022</last_update_submitted>
  <last_update_submitted_qc>April 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Fudan University</investigator_affiliation>
    <investigator_full_name>Xichun Hu</investigator_full_name>
    <investigator_title>Director of the Department of Medical Oncology</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast Neoplasms</mesh_term>
    <mesh_term>Triple Negative Breast Neoplasms</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/NCT03251313
org study id: Fudan-P1-201701
nct id: NCT03251313
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a Phase I dose escalation trial to assess dose-limiting toxicity (DLT) and MTD of
      JS001+GP in advanced/metastatic TNBC patients, and to determine the recommended Phase II dose
      and the best combination regimen.
There will be 3 stages in this trial. Stage 1 is the dose escalation stage. JS001 will be
      tested in combination with GP in 3 dose levels.

      Level 1: 120mg Level 2: 240mg Level 3: 480mg Patients will receive JS001+GP for 6 cycles and
      JS001 maintenance therapy for up to approximately 2 years.

      JS001 will be given on d1 every 3 weeks with GP and every 2 weeks in maintenance therapy.

      The first group of participants will receive the lowest dose level of JS001 at 120mg. Each
      new group will receive a higher dose of JS001 than the group before it until 480mg.

      Stage 2 is the dose expansion stage. Dose expansion will be carried out to expand to 12
      patients in the highest dose level at which the patient can tolerate well. This dose will
      also be recommended as phase 2 dose(RP2D).

      Stage 3 is the sequential treatment stage. Patients receive 6 cycles of GP without JS001 and
      then receive JS001 maintenance therapy for up to approximately 2 years.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum Tolerated Dose (MTD) of JS001 when combined with GP
time frame: 3 weeks
description: If 1/6 patients has grade 3 or higher toxicity then escalation proceeds, if 2/6 has grade 3 or greater toxicity then this is declared MTD.
measure: Peak Plasma Concentration (Cmax)
time frame: 85 days
description: Cmax of JS001
measure: Area under the plasma concentration versus time curve (AUC)
time frame: 85 days
description: AUC of JS001
measure: other pharmacokinetics(PK) characteristics of JS001+GP
time frame: 85 days
description: half life of JS001
measure: Incidence of Treatment-Emergent Adverse Events
time frame: 85 days
description: Incidence of Adverse Events that need to be treated immediately
measure: Incidence of Severe Adverse Events
time frame: 85 days
description: Incidence of Adverse Events that cause hospitalization, inability, death, etc
measure: objective response rate of JS001+GP
time frame: 1 year
description: objective response rate(%) is the sum of CR(complete remission) rate and PR(partial remission) rate
measure: disease control rate of JS001+GP
time frame: 1 year
description: disease control rate(%) is the sum of CR rate and PR rate and SD(stable disease) rate for more than 6 weeks
measure: duration of regression of JS001+GP
time frame: 1 year
description: duration of regression(months) is the time interval from randomization to disease progression
measure: time to regression of JS001+GP
time frame: 1 year
description: time to regression(months) is the time interval from randomization to disease regressin
measure: progression free survival of JS001+GP
time frame: 1 year
description: progression free survival(months) is the time interval from randomization to disease progression or death from any reason
measure: overall survival of JS001+GP
time frame: 1 year
description: overall survival(months) is the time interval between randomization and death from any reason
measure: best combination regimen
time frame: 1 year
description: Is JS001 combined with GP or GP followed by JS001 better in safety (incidence of grade 3-4 toxicity) and efficacy(Response Rate and PFS)
arm group label: JS001 120mg+GP
arm group type: Experimental
description: Level 1: JS001 120mg +GP q3w,*6 cycles, then JS001 120mg q3w for maintenance therapy for up to approximately 2 years.
arm group label: JS001 240mg+GP
arm group type: Experimental
description: Level 2: JS001 240mg +GP q3w,*6 cycles, then JS001 240mg q3w for maintenance therapy for up to approximately 2 years.
arm group label: JS001 480mg +GP
arm group type: Experimental
description: Level 3: JS001 480mg+GP q3w,*6 cycles, then JS001 480mg q3w for maintenance therapy for up to approximately 2 years.
arm group label: GP followed by JS001
arm group type: Experimental
description: sequential treatment: Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years. JS001 will be given at RP2D.
intervention type: Combination Product
intervention name: JS001 120mg+GP
description: In this arm, JS001 120mg will be given at d1; Gem 1000mg/m2 d2,9; DDP(cisplatin) 75mg/m2 d2
arm group label: JS001 120mg+GP
intervention type: Combination Product
intervention name: JS001 240mg+GP
description: In this arm, JS001 240mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2
arm group label: JS001 240mg+GP
intervention type: Combination Product
intervention name: JS001 480mg+GP
description: In this arm, JS001 480mg will be given at d1; Gem 1000mg/m2 d2,9; DDP 75mg/m2 d2
arm group label: JS001 480mg +GP
intervention type: Combination Product
intervention name: GP followed by JS001
description: In this arm,Patients receive 6 cycles of GP without JS001 and then receive JS001 maintenance therapy for up to approximately 2 years. JS001 will be given at RP2D.
arm group label: GP followed by JS001
criteria: 
gender: Female
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Xichun Hu, MD& PhD
role: Principal Investigator
affiliation: Fudan University
facility: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Fudan University
investigator full name: Xichun Hu
investigator title: Director of the Department of Medical Oncology
mesh term: Breast Neoplasms
mesh term: Triple Negative Breast Neoplasms
sharing ipd: Undecided