<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/NCT04477772</url>
  </required_header>
  <id_info>
    <org_study_id>JS004-002-I</org_study_id>
    <nct_id>NCT04477772</nct_id>
  </id_info>
  <brief_title>A Phase I Clinical Study of JS004 in Subjects With Recurrent/Refractory Malignant Lymphoma of China</brief_title>
  <official_title>A Phase I Clinical Study of Recombinant Humanized Anti-BTLA Monoclonal Antibody (JS004) in Patients With Recurrent/Refractory Malignant Lymphoma</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>No</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>
      A First-in-human, dose-escalation, dose-expansion phase I clinical study of JS004 in subjects&#xD;
      with recurrent/refractory malignant lymphoma in China, to evaluate the safety, tolerbility,&#xD;
      PK, immunogenicity,antitumor activity and biomarkers of JS004, to define MTD and RP2D of&#xD;
      JS004. A cycle is 21 days(3 weeks) which includes JS004 being administered IV Q3W and JS004&#xD;
      combine with JS001 being administered IV Q3W. All patients will be treated until disease&#xD;
      progression per Lugano response critieria 2014 for Lymphoma or intolerable toxicity per CTCAE&#xD;
      5.0, withdrawal of consent, or end of the study, whichever occurs first. Disease progression&#xD;
      must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of&#xD;
      progression.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 17, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2024</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants and severiaty with treatment-related Adverse events as assessed by CTCAE V5.0</measure>
    <time_frame>2 Years</time_frame>
    <description>Safety and Tolerability</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) per Lugano response critieria 2014 for Lymphoma</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) per Lugano response critieria 2014 for Lymphoma</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) per Lugano response critieria 2014 for Lymphoma</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progrssion-free survival (PFS) per Lugano response critieria 2014 for Lymphoma</measure>
    <time_frame>2 Years</time_frame>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">170</enrollment>
  <condition>Recurrent/Refractory Malignant Lymphoma</condition>
  <arm_group>
    <arm_group_label>1mg/kg JS004, Q3W until to 2 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation, enrolled 3-6 subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>3mg/kg JS004, Q3W until to 2 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 9 subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>10mg/kg JS004, Q3W until to 2 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation, enrolled 3-6 subjects</description>
  </arm_group>
  <arm_group>
    <arm_group_label>200mg, Q3W until to 2 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose expansion, enrolled 9 subjects and indication expansion if RP2D is 200mg</description>
  </arm_group>
  <arm_group>
    <arm_group_label>240mg JS004+100mg JS001, Q3W until to 2 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>240mg JS004+200mg JS001, Q3W until to 2 years</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion</intervention_name>
    <description>Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.</description>
    <arm_group_label>10mg/kg JS004, Q3W until to 2 years</arm_group_label>
    <arm_group_label>1mg/kg JS004, Q3W until to 2 years</arm_group_label>
    <arm_group_label>200mg, Q3W until to 2 years</arm_group_label>
    <arm_group_label>240mg JS004+100mg JS001, Q3W until to 2 years</arm_group_label>
    <arm_group_label>240mg JS004+200mg JS001, Q3W until to 2 years</arm_group_label>
    <arm_group_label>3mg/kg JS004, Q3W until to 2 years</arm_group_label>
    <other_name>TAB004</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Drug：JS001, Intravenous infusion</intervention_name>
    <description>Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.</description>
    <arm_group_label>240mg JS004+100mg JS001, Q3W until to 2 years</arm_group_label>
    <arm_group_label>240mg JS004+200mg JS001, Q3W until to 2 years</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        1.Able to understand and sign informed consent voluntarily&#xD;
&#xD;
        2.18-70 years old&#xD;
&#xD;
        3.Pathologically confirmed malignant lymphoma&#xD;
&#xD;
        4.ECOG PS: 0-1&#xD;
&#xD;
        5.Expected survival ≥12 weeks&#xD;
&#xD;
        6.At least one measurable lesion per Lugano response critieria 2014 for Lymphoma&#xD;
&#xD;
        7.Adequate organ and marrow function, as defined below:&#xD;
&#xD;
        ANC≥1.5×109/L;&#xD;
&#xD;
        PLT≥100×109/L and ≥75×109/L for subjects with bone marrow involvement;&#xD;
&#xD;
        Hb≥90 g/L;&#xD;
&#xD;
        TBIL≤1.5 ULN, ≤2 ULN in those with hep109atic metastasis, except subjects with documented&#xD;
        Gilbert's syndrome who must have a baseline conjugated bilirubin ≤3.0 mg/dL;&#xD;
&#xD;
        AST and ALT≤2.5 ULN, ≤5 ULN in those with hepatic metastasis;&#xD;
&#xD;
        Cr≤1.5 UL, or creatinine clearance≥50mL/min for subject;&#xD;
&#xD;
        INR ≤2 ULN and aPTT≤1.5×ULN for those with no prior anticoagulant therapy.&#xD;
&#xD;
        8.According to Fridericia's principle, QTC results need to match : Male≤450 ms，Female≤470&#xD;
        ms&#xD;
&#xD;
        9.Females of childbearing potential need to use effective contraception&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with known allergy to macromolecular protein preparations or JS004 components&#xD;
&#xD;
          2. Prior exposure to anti-BTLA or anti-HVEM antibodies&#xD;
&#xD;
          3. Enrolled in other clinical studies within 4 weeks prior to the first dose of study&#xD;
             treatment&#xD;
&#xD;
          4. Major surgery within 4 weeks prior to the first dose of study treatmentor still&#xD;
             recovering from prior surgery&#xD;
&#xD;
          5. Patients who discontinued previous immunotherapy due to immune-related adverse&#xD;
             reactions&#xD;
&#xD;
          6. Immunosuppressive agents have been used within 4 weeks prior to the first dose of&#xD;
             study treatment&#xD;
&#xD;
          7. Prior allogeneic bone marrow transplantation or solid organ transplantation&#xD;
&#xD;
          8. Live attenuated vaccine be administered 30 days before the first dose of study&#xD;
             treatment&#xD;
&#xD;
          9. Two or more malignancies developed within 5 years prior to first dose of study&#xD;
             treatment&#xD;
&#xD;
         10. The patients have symptomatic, untreated, or requiring ongoing treatment central&#xD;
             nervous system (CNS) metastases&#xD;
&#xD;
         11. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to&#xD;
             baseline or to NCI-CTCAE v5.0 Grade 0 or 1, or to levels dictated in the&#xD;
             inclusion/exclusion criteria with the exception of alopecia.Subjects with irreversible&#xD;
             toxicity that is not reasonably expected to be exacerbated by TAB004 may be included&#xD;
             (e.g., hearing loss) after consultation with the medical monitor.&#xD;
&#xD;
         12. Autoimmune disease within the previous 2 years&#xD;
&#xD;
         13. A history of rapid allergic reaction, eczema, or asthma beyond the control of topical&#xD;
             corticosteroids&#xD;
&#xD;
         14. A history of primary immunodeficiency&#xD;
&#xD;
         15. Concomitant disease that is not under control, including but not limited to:&#xD;
             persistent or active infection, unexplained fever &gt; 38.5°C, or heart disease, active&#xD;
             peptic ulcer disease or gastritis&#xD;
&#xD;
         16. A history of active inflammatory bowel disease&#xD;
&#xD;
         17. HIV(+)&#xD;
&#xD;
         18. Patients with evidence of hepatitis B virus (HBV) or hepatitis C virus (HCV) infection&#xD;
&#xD;
         19. Pregnant or lactating woman&#xD;
&#xD;
         20. Patients with vitiligo, alopecia, and hormonal replacement therapy have controlled&#xD;
             endocrine defects&#xD;
&#xD;
         21. Any other medical factors that may affect subjects' rights, safety, compliance,&#xD;
             ability to sign informed consent, and interpretation of study results.&#xD;
&#xD;
         22. Have a history of psychotropic drug abuse and unable to withdraw or have mental&#xD;
             disorders.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Beijing Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>July 16, 2020</study_first_submitted>
  <study_first_submitted_qc>July 17, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 20, 2020</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 1, 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>Lymphoma</mesh_term>
    <mesh_term>Recurrence</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>
  <!-- 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/NCT04477772
org study id: JS004-002-I
nct id: NCT04477772
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A First-in-human, dose-escalation, dose-expansion phase I clinical study of JS004 in subjects
      with recurrent/refractory malignant lymphoma in China, to evaluate the safety, tolerbility,
      PK, immunogenicity,antitumor activity and biomarkers of JS004, to define MTD and RP2D of
      JS004. A cycle is 21 days(3 weeks) which includes JS004 being administered IV Q3W and JS004
      combine with JS001 being administered IV Q3W. All patients will be treated until disease
      progression per Lugano response critieria 2014 for Lymphoma or intolerable toxicity per CTCAE
      5.0, withdrawal of consent, or end of the study, whichever occurs first. Disease progression
      must be confirmed at least 4 weeks but no longer than 8 weeks after initial documentation of
      progression.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants and severiaty with treatment-related Adverse events as assessed by CTCAE V5.0
time frame: 2 Years
description: Safety and Tolerability
measure: Objective Response Rate (ORR) per Lugano response critieria 2014 for Lymphoma
time frame: 2 Years
measure: Duration of Response (DOR) per Lugano response critieria 2014 for Lymphoma
time frame: 2 Years
measure: Disease Control Rate (DCR) per Lugano response critieria 2014 for Lymphoma
time frame: 2 Years
measure: Progrssion-free survival (PFS) per Lugano response critieria 2014 for Lymphoma
time frame: 2 Years
arm group label: 1mg/kg JS004, Q3W until to 2 years
arm group type: Experimental
description: Dose escalation, enrolled 3-6 subjects
arm group label: 3mg/kg JS004, Q3W until to 2 years
arm group type: Experimental
description: Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 9 subjects
arm group label: 10mg/kg JS004, Q3W until to 2 years
arm group type: Experimental
description: Dose escalation, enrolled 3-6 subjects
arm group label: 200mg, Q3W until to 2 years
arm group type: Experimental
description: Dose expansion, enrolled 9 subjects and indication expansion if RP2D is 200mg
arm group label: 240mg JS004+100mg JS001, Q3W until to 2 years
arm group type: Experimental
description: Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm
arm group label: 240mg JS004+200mg JS001, Q3W until to 2 years
arm group type: Experimental
description: Dose escalation, enrolled 3-6 subjects; Dose expansion, enrolled 6-9 subjects and indication expansion if RP2D is confirmed this arm
intervention type: Biological
intervention name: JS004 , Recombinant humanized IgG4k monoclonal antibody specific to BTLA for injection Intravenous infusion
description: Part A: including dose escalation (1mg/kg JS004; 3mg/lg JS004; 10mg/kg JS004), dose expansion (3mg/kg JS004 and 200mg JS004) and indication expansion. Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.
arm group label: 10mg/kg JS004, Q3W until to 2 years
arm group label: 1mg/kg JS004, Q3W until to 2 years
arm group label: 200mg, Q3W until to 2 years
arm group label: 240mg JS004+100mg JS001, Q3W until to 2 years
arm group label: 240mg JS004+200mg JS001, Q3W until to 2 years
arm group label: 3mg/kg JS004, Q3W until to 2 years
other name: TAB004
intervention type: Biological
intervention name: Drug：JS001, Intravenous infusion
description: Part B: including dose escalation (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001), dose expansion (240mg JS004+100mg JS001; 240mg JS004+ 200mg JS001) and indication expansion.
arm group label: 240mg JS004+100mg JS001, Q3W until to 2 years
arm group label: 240mg JS004+200mg JS001, Q3W until to 2 years
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Lymphoma
mesh term: Recurrence
mesh term: Antibodies
mesh term: Antibodies, Monoclonal