<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/NCT03789604</url>
  </required_header>
  <id_info>
    <org_study_id>CS1001-302</org_study_id>
    <nct_id>NCT03789604</nct_id>
  </id_info>
  <brief_title>A Study of CS1001 in Subjects With Stage IV Non-Small Cell Lung Cancer</brief_title>
  <official_title>A Multi-Center, Randomized, Double-Blind, Phase III Study of Platinum-Containing Chemotherapy With or Without CS1001 in Stage IV Non-Small Cell Lung Cancer Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CStone Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>CStone Pharmaceuticals</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 multi-center, randomized, double-blind, phase III study to evaluate the efficacy&#xD;
      and safety of CS1001 in combination with platinum-containing chemotherapy versus placebo in&#xD;
      combination with chemotherapy in first-line treatment-naive subjects with stage IV non-small&#xD;
      cell lung cancer (NSCLC).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 13, 2018</start_date>
  <completion_date type="Anticipated">June 30, 2025</completion_date>
  <primary_completion_date type="Actual">May 15, 2023</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free survival (PFS) in all subjects evaluated by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1</measure>
    <time_frame>up to approximately 5 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>up to approximately 7 years</time_frame>
    <description>OS defined as the time from randomization to all-cause death.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS assessed by BICR</measure>
    <time_frame>up to approximately 5 years</time_frame>
    <description>PFS defined as the time from randomization to the first occurrence of disease progression or all-cause death (whichever occurs first), as determined by the BICR according to RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS in subgroup of participants with PD-L1 Expression≥1%, as determined by the investigator</measure>
    <time_frame>up to approximately 5 years</time_frame>
    <description>PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with PD-L1 expression ≥1% defined by the SP263 immunohistochemistry (IHC) assay.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR) assessed by the investigator according to RECIST v1.1</measure>
    <time_frame>up to approximately 5 years</time_frame>
    <description>ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions &gt;=4 weeks apart, as determined by the investigator according to RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR) assessed by the investigator according to RECIST v1.1</measure>
    <time_frame>up to approximately 5 years</time_frame>
    <description>DOR defined as the time between the date of the earliest qualifying response and the date of progressive disease or all-cause death, whichever occurs first, as determined by the investigator according to RECIST v1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Safety and tolerability of CS1001 or placebo in combination with platinum-based chemotherapy</measure>
    <time_frame>up to approximately 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics (PK) and immunogenecity of CS1001</measure>
    <time_frame>up to approximately 5 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Efficacy of CS1001 monotherapy in subjects cross over to receive CS1001 who experienced progressive disease after assigned to the placebo group in the double-blind phase (CS1001 or placebo in combination with chemotherapy)</measure>
    <time_frame>up to approximately 5 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">479</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>CS1001 monoclonal antibody</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>CS1001 placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CS1001 monoclonal antibody</intervention_name>
    <description>Participant will receive CS1001 monoclonal antibody 1200 mg by intravenous infusion every 3 weeks, for up to 24 months; Drug Carboplatin on Day 1 of each 21-day cycle; Drug Pemetrexed on Day 1 of each 21-day cycle; Drug Paclitaxel on Day 1 of each 21-day cycle</description>
    <arm_group_label>CS1001 monoclonal antibody</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CS1001 placebo</intervention_name>
    <description>Participant will receive CS1001 placebo 1200 mg by intravenous infusion every 3 weeks, for up to 24 months; Drug Carboplatin on Day 1 of each 21-day cycle; Drug Pemetrexed on Day 1 of each 21-day cycle; Drug Paclitaxel on Day 1 of each 21-day cycle</description>
    <arm_group_label>CS1001 placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing to participate in this trial; fully understand and informed of this trial, and&#xD;
             able to provide written informed consent form (ICF).&#xD;
&#xD;
          2. 18-75 years of age (18 and 75 included) on the day of signing ICF.&#xD;
&#xD;
          3. Histologically or cytologically confirmed stage IV non-small cell lung cancer (staged&#xD;
             according to the 8th International Association for the Study of Lung Cancer (IASLC)&#xD;
             classification.&#xD;
&#xD;
          4. Subjects haven't received systemic treatment for advanced/metastatic NSCLC.&#xD;
&#xD;
          5. Measurable target lesion evaluated by investigators according to RECIST v1.1.&#xD;
&#xD;
          6. ECOG PS of 0-1.&#xD;
&#xD;
          7. Life expectancy ≥ 12 weeks.&#xD;
&#xD;
          8. Subject with prior anti-cancer treatment can only be enrolled when all toxicities&#xD;
             except for hearing loss, alopecia and fatigue, of prior anti-cancer treatment has&#xD;
             recovered to ≤ Grade 1 according to National Cancer Institute [NCI] Common Terminology&#xD;
             Criteria for Adverse Events (CTCAE) v4.03.&#xD;
&#xD;
          9. Subjects must have adequate organ function.&#xD;
&#xD;
         10. Women of childbearing potential (WOBPC, as defined in section 13.5) must have a&#xD;
             negative pregnancy test ≤7 days prior to the first dose of investigational product.&#xD;
             WOBCP or fertile men and their WOBCP partners must agree to use an effective method of&#xD;
             birth control from providing signed ICF and for 6 months after last dose of&#xD;
             investigational product.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed small cell lung cancer or containing small cell component.&#xD;
&#xD;
          2. Subjects with current active autoimmune disease or prior history of autoimmune&#xD;
             disease.&#xD;
&#xD;
          3. Malignancies other than NSCLC within 5 years prior to randomization.&#xD;
&#xD;
          4. Known history of human immunodefiency virus (HIV) infection and/or acquired immune&#xD;
             deficiency syndrome.&#xD;
&#xD;
          5. Subject with active hepatitis B or hepatitis C.&#xD;
&#xD;
          6. Subjects with known history of alcoholism or drugs abuse.&#xD;
&#xD;
          7. Has a known hypersensitivity to any component of study treatment, for example&#xD;
             pemetrexed, cisplatin, carboplatin or other platinum compounds.&#xD;
&#xD;
          8. Subjects with other conditions that in the investigator's opinion may influence&#xD;
             subject's compliance or make subjects not suitable for participating in this trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shanghai Pulmonary Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 28, 2018</study_first_posted>
  <last_update_submitted>July 31, 2023</last_update_submitted>
  <last_update_submitted_qc>July 31, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 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>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</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/NCT03789604
org study id: CS1001-302
nct id: NCT03789604
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This is a multi-center, randomized, double-blind, phase III study to evaluate the efficacy
      and safety of CS1001 in combination with platinum-containing chemotherapy versus placebo in
      combination with chemotherapy in first-line treatment-naive subjects with stage IV non-small
      cell lung cancer (NSCLC).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Progression-free survival (PFS) in all subjects evaluated by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
time frame: up to approximately 5 years
measure: Overall Survival (OS)
time frame: up to approximately 7 years
description: OS defined as the time from randomization to all-cause death.
measure: PFS assessed by BICR
time frame: up to approximately 5 years
description: PFS defined as the time from randomization to the first occurrence of disease progression or all-cause death (whichever occurs first), as determined by the BICR according to RECIST v1.1
measure: PFS in subgroup of participants with PD-L1 Expression≥1%, as determined by the investigator
time frame: up to approximately 5 years
description: PFS after randomization as determined by the investigator according to RECIST v1.1 in the subgroup of patients with PD-L1 expression ≥1% defined by the SP263 immunohistochemistry (IHC) assay.
measure: Objective Response Rate (ORR) assessed by the investigator according to RECIST v1.1
time frame: up to approximately 5 years
description: ORR, defined as the proportion of patients with a complete response (CR) or partial response (PR) on two consecutive occasions >=4 weeks apart, as determined by the investigator according to RECIST v1.1.
measure: Duration of response (DOR) assessed by the investigator according to RECIST v1.1
time frame: up to approximately 5 years
description: DOR defined as the time between the date of the earliest qualifying response and the date of progressive disease or all-cause death, whichever occurs first, as determined by the investigator according to RECIST v1.1.
measure: Safety and tolerability of CS1001 or placebo in combination with platinum-based chemotherapy
time frame: up to approximately 5 years
measure: Pharmacokinetics (PK) and immunogenecity of CS1001
time frame: up to approximately 5 years
measure: Efficacy of CS1001 monotherapy in subjects cross over to receive CS1001 who experienced progressive disease after assigned to the placebo group in the double-blind phase (CS1001 or placebo in combination with chemotherapy)
time frame: up to approximately 5 years
arm group label: CS1001 monoclonal antibody
arm group type: Experimental
arm group label: CS1001 placebo
arm group type: Placebo Comparator
intervention type: Biological
intervention name: CS1001 monoclonal antibody
description: Participant will receive CS1001 monoclonal antibody 1200 mg by intravenous infusion every 3 weeks, for up to 24 months; Drug Carboplatin on Day 1 of each 21-day cycle; Drug Pemetrexed on Day 1 of each 21-day cycle; Drug Paclitaxel on Day 1 of each 21-day cycle
arm group label: CS1001 monoclonal antibody
intervention type: Biological
intervention name: CS1001 placebo
description: Participant will receive CS1001 placebo 1200 mg by intravenous infusion every 3 weeks, for up to 24 months; Drug Carboplatin on Day 1 of each 21-day cycle; Drug Pemetrexed on Day 1 of each 21-day cycle; Drug Paclitaxel on Day 1 of each 21-day cycle
arm group label: CS1001 placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Antibodies
mesh term: Antibodies, Monoclonal