<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/NCT04405674</url>
  </required_header>
  <id_info>
    <org_study_id>BGB-A317-2001-IIT</org_study_id>
    <nct_id>NCT04405674</nct_id>
  </id_info>
  <brief_title>Tislelizumab Combined With Chemotherapy With or Without Bevacizumab in TKI-Resistant EGFR-Mutated Non-squamous NSCLC</brief_title>
  <official_title>A Phase II Two Cohorts Prospective Study to Evaluate the Efficacy and Safety of Tislelizumab Combined With Chemotherapy With or Without Bevacizumab in Non-squamous NSCLC With EGFR Sensitizing Mutation Who Failed EGFR TKI Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Chest Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Chest Hospital</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A phase II, open-label, multicenter, two cohorts, prospective clinical study to investigate&#xD;
      the efficacy and safety of tislelizumab (anti-pd1 antibody) combined with chemotherapy with&#xD;
      or without bevacizumab in non-squamous non-small cell lung cancer patients with EGFR&#xD;
      sensitizing mutation who failed EGFR TKI (Epidermal Growth Factor Receptor Tyrosine Kinase&#xD;
      Inhibitor) therapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Although EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated&#xD;
      NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an&#xD;
      anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with&#xD;
      advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the&#xD;
      efficacy and safety of tislelizumab plus carboplatin and Nab-paclitaxel（cohort 1）or&#xD;
      tislelizumab plus Nab-paclitaxel and bevacizumab （cohort 2） in EGFR-mut nsq-NSCLC pts failed&#xD;
      to EGFR TKI therapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Anticipated">March 2025</completion_date>
  <primary_completion_date type="Anticipated">April 2022</primary_completion_date>
  <phase>Phase 2</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>1-Year Progression-Free Survival Rate (1-Year PFS Rate)</measure>
    <time_frame>up to 24 months after enrollment or study close</time_frame>
    <description>Progression-free survival (per RECIST 1.1) is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first. Subjects who do not have disease progression will be censored at their last valid tumor assessment. PFS rate at 1 year as estimated by Kaplan-Meier method.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>up to 24 months after enrollment or study close</time_frame>
    <description>Progression-free survival (PFS per RECIST 1.1) is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective Respond Rate (ORR)</measure>
    <time_frame>up to 24 months after enrollment or study close</time_frame>
    <description>ORR (per RECIST 1.1) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>up to 24 months after enrollment or study close</time_frame>
    <description>DCR (per RECIST 1.1) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR), or stable disease (SD).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>up to 24 months after enrollment or study close</time_frame>
    <description>OS is defined as the time from the starting date of study drug to the date of death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DoR)</measure>
    <time_frame>up to 24 months after enrollment or study close</time_frame>
    <description>DoR (per RECIST 1.1) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Non Small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Tislelizumab plus chemotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tislelizumab plus Carboplatin/Nab-paclitaxel as induction treatment and followed by Tislelizumab plus pemetrexed as maintenance treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Tislelizumab plus chemotherapy plus Bevacizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tislelizumab plus Nab-paclitaxel and Bevacizumab as induction treatment and followed by Tislelizumab plus Bevacizumab as maintenance treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tislelizumab</intervention_name>
    <description>Tislelizumab 200mg administered intravenously (IV) on Day 1 of each 21-day cycle</description>
    <arm_group_label>Tislelizumab plus chemotherapy</arm_group_label>
    <arm_group_label>Tislelizumab plus chemotherapy plus Bevacizumab</arm_group_label>
    <other_name>BGB-A317</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin AUC 5 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles</description>
    <arm_group_label>Tislelizumab plus chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Pemetrexed 500mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle</description>
    <arm_group_label>Tislelizumab plus chemotherapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Bevacizumab</intervention_name>
    <description>Bevacizumab 7.5mg/kg administered intravenously (IV) on Day 1 of each 21-day cycle</description>
    <arm_group_label>Tislelizumab plus chemotherapy plus Bevacizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nab paclitaxel</intervention_name>
    <description>Nab-paclitaxel 260mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles</description>
    <arm_group_label>Tislelizumab plus chemotherapy</arm_group_label>
    <arm_group_label>Tislelizumab plus chemotherapy plus Bevacizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed, locally advanced (Stage IIIB/C) not&#xD;
             amenable to curative surgery or radiotherapy, or metastatic (Stage IV) non-squamous&#xD;
             NSCLC according to American Joint Committee on Cancer, 8th Edition.&#xD;
&#xD;
          2. Documentation of tumor EGFR sensitizing mutation before EGFR TKI treatment, including&#xD;
             19del, L858R, G719X, S786I and L861Q.&#xD;
&#xD;
          3. Disease progression after treatment with an EGFR TKI therapy: 1) Patients previously&#xD;
             treated with 1st or 2nd generation EGFR TKI (e.g.&#xD;
             erlotinib/afatinib/gefitinib/icotinib) are required to provide specimens after PD to&#xD;
             confirmed absence of EGFR T790M mutation; 2) Patients with confirmed acquired T790M&#xD;
             mutation after 1st or 2nd generation EGFR TKI (e.g.&#xD;
             erlotinib/afatinib/gefitinib/icotinib) are required to have 3rd generation EGFR TKI&#xD;
             (e.g. osimertinib) treatment failure prior to enrollment; 3) Patients previously&#xD;
             failed from 3rd generation EGFR TKI (e.g. osimertinib) treatment as 1st line therapy&#xD;
             are eligible regardless of their EGFR T790M mutation status.&#xD;
&#xD;
          4. ECOG (Eastern Cooperative Oncology Group) performance status ≤ 1.&#xD;
&#xD;
          5. Life expectancy ≥ 3 months.&#xD;
&#xD;
          6. Adequate organ function&#xD;
&#xD;
          7. Able to provide written informed consent by the patient or by the patient's legally&#xD;
             acceptable representative and can understand and agree to comply with the requirements&#xD;
             of the study.&#xD;
&#xD;
          8. 18 to 75 years old on the day of signing the ICF (Informed Consent Form).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Received prior therapies targeting PD-1, PD-L1, CTLA-4 or other immune checkpoints.&#xD;
&#xD;
          2. Received prior platinum-based chemotherapy for advanced disease.&#xD;
&#xD;
          3. Patients who have received prior systemic anti-vascular therapy (e.g., bevacizumab and&#xD;
             small molecule VEGFR inhibitors) for advanced disease (Cohort 2)&#xD;
&#xD;
          4. Received EGFR TKI treatment within 2 weeks&#xD;
&#xD;
          5. Treatment with any approved systemic anti-cancer therapy or systemic&#xD;
             immune-stimulatory agents (including but not limited to interferons, interleukin IL-2,&#xD;
             and tumor necrosis factor) within 28 days prior to initiation of study treatment.&#xD;
&#xD;
          6. Clinically uncontrolled pleural effusion or ascites that requires pleurocentesis or&#xD;
             abdominal tapping for drainage within 2 weeks prior to initiation of study treatment.&#xD;
&#xD;
          7. Active leptomeningeal disease or uncontrolled brain metastasis.&#xD;
&#xD;
          8. History of allergic reactions to any study drugs.&#xD;
&#xD;
          9. CrCl &lt; 45 mL/min&#xD;
&#xD;
         10. Patients with active viral hepatitis that requires treatment.&#xD;
&#xD;
         11. Active autoimmune diseases that requires treatment and may affect study treatment&#xD;
             estimated by investigator.&#xD;
&#xD;
         12. Any condition that required systemic treatment with either corticosteroids or any&#xD;
             other immunosuppressive medication that may affect study treatment estimated by&#xD;
             investigator.&#xD;
&#xD;
         13. Severe chronic or active infections requiring systemic antibacterial, antifungal or&#xD;
             antiviral therapy.&#xD;
&#xD;
         14. History of hemoptysis, i.e., coughing up at least one-half teaspoon of fresh blood,&#xD;
             within 3 months prior to enrollment. (Cohort 2)&#xD;
&#xD;
         15. Imaging shows tumor invasion of a large vessel (e.g., pulmonary artery or superior&#xD;
             vena cava) that the investigator determines is at risk for bleeding. (Cohort 2)&#xD;
&#xD;
         16. Had minor surgical procedures, such as tube placement, within 48 hours prior to first&#xD;
             bevacizumab treatment. (Cohort 2)&#xD;
&#xD;
         17. Recently treated with a full dose oral or parenteral anticoagulant or thrombolytic&#xD;
             agent. Prophylactic using anticoagulants is allowed. (Cohort 2)&#xD;
&#xD;
         18. History or test results indicating an inherited bleeding tendency or coagulation&#xD;
             disorder that may increase the risk of bleeding (cohort 2)&#xD;
&#xD;
         19. uncontrolled hypertension (systolic blood pressure &gt;150 mmHg and/or diastolic blood&#xD;
             pressure &gt;100 mmHg) (cohort 2)&#xD;
&#xD;
         20. Clinically meaningful (e.g., active) cardiovascular disease that, in the judgment of&#xD;
             the investigator, is intolerant to bevacizumab therapy (cohort 2)&#xD;
&#xD;
         21. Non-cured wound, peptic ulcer in active phase, or fracture (cohort 2)&#xD;
&#xD;
         22. History of abdominal fistula, gastrointestinal perforation, intra-abdominal abscess or&#xD;
             thrombotic disease within 6 months judged by the investigator to be intolerant to&#xD;
             bevacizumab treatment (Cohort 2)&#xD;
&#xD;
         23. With a history of interstitial lung disease, non-infectious pneumonitis, or&#xD;
             uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis,&#xD;
             acute lung diseases, etc.&#xD;
&#xD;
         24. Have known human immunodeficiency virus (HIV) infection.&#xD;
&#xD;
         25. Any major surgical procedure requiring general anesthesia ≤ 28 days before initiation&#xD;
             of study treatment.&#xD;
&#xD;
         26. Underlying medical conditions (including laboratory abnormalities) or alcohol or drug&#xD;
             abuse or dependence that would be unfavorable for the administration of study drug or&#xD;
             affect the explanation of drug toxicity or AEs (Adverse Events) or result in&#xD;
             insufficient or might impair compliance with study conduct.&#xD;
&#xD;
         27. Concurrent participation in another clinical study.&#xD;
&#xD;
         28. Pregnant or lactating women, or male and female patients who plan to have children&#xD;
             during the study period. -&#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 Chest Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200000</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Baohui Han</last_name>
      <phone>8618930858216</phone>
      <email>18930858216@163.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 25, 2020</study_first_submitted>
  <study_first_submitted_qc>May 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>November 19, 2021</last_update_submitted>
  <last_update_submitted_qc>November 19, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 22, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Chest Hospital</investigator_affiliation>
    <investigator_full_name>Baohui Han</investigator_full_name>
    <investigator_title>Professor, Director of Pulmonary Medicine at Shanghai Chest Hospital</investigator_title>
  </responsible_party>
  <keyword>Tislelizumab</keyword>
  <keyword>PD-1</keyword>
  <keyword>Chemotherapy</keyword>
  <keyword>EGFR mutation</keyword>
  <keyword>Non small cell lung cancer</keyword>
  <keyword>Bevacizumab</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>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Paclitaxel</mesh_term>
    <mesh_term>Bevacizumab</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Tislelizumab</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/NCT04405674
org study id: BGB-A317-2001-IIT
nct id: NCT04405674
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: Yes
A phase II, open-label, multicenter, two cohorts, prospective clinical study to investigate
      the efficacy and safety of tislelizumab (anti-pd1 antibody) combined with chemotherapy with
      or without bevacizumab in non-squamous non-small cell lung cancer patients with EGFR
      sensitizing mutation who failed EGFR TKI (Epidermal Growth Factor Receptor Tyrosine Kinase
      Inhibitor) therapy.
Although EGFR tyrosine kinase inhibitors (TKI) have improved the survival of EGFR mutated
      NSCLC pts, drug resistance inevitably develops in almost all pts. Tislelizumab (tis), an
      anti-PD-1 mAb, has shown improved efficacy when combined with chemotherapy in pts with
      advanced EGFR-wt NSCLC with a tolerable safety profile. This study aims to evaluate the
      efficacy and safety of tislelizumab plus carboplatin and Nab-paclitaxel（cohort 1）or
      tislelizumab plus Nab-paclitaxel and bevacizumab （cohort 2） in EGFR-mut nsq-NSCLC pts failed
      to EGFR TKI therapies.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: 1-Year Progression-Free Survival Rate (1-Year PFS Rate)
time frame: up to 24 months after enrollment or study close
description: Progression-free survival (per RECIST 1.1) is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first. Subjects who do not have disease progression will be censored at their last valid tumor assessment. PFS rate at 1 year as estimated by Kaplan-Meier method.
measure: Progression-Free Survival (PFS)
time frame: up to 24 months after enrollment or study close
description: Progression-free survival (PFS per RECIST 1.1) is defined as the time from the starting date of study drug to the date of first documentation of disease progression or death, whichever occurs first.
measure: Objective Respond Rate (ORR)
time frame: up to 24 months after enrollment or study close
description: ORR (per RECIST 1.1) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR).
measure: Disease Control Rate (DCR)
time frame: up to 24 months after enrollment or study close
description: DCR (per RECIST 1.1) is defined as the proportion (%) of patients with at least one visit response of complete response (CR) or partial response (PR), or stable disease (SD).
measure: Overall Survival (OS)
time frame: up to 24 months after enrollment or study close
description: OS is defined as the time from the starting date of study drug to the date of death due to any cause.
measure: Duration of Response (DoR)
time frame: up to 24 months after enrollment or study close
description: DoR (per RECIST 1.1) is defined as the time from the date for first documented response of complete response (CR) or partial response (PR) to the date of first documented of disease progression or death, whichever occurs first.
arm group label: Tislelizumab plus chemotherapy
arm group type: Experimental
description: Tislelizumab plus Carboplatin/Nab-paclitaxel as induction treatment and followed by Tislelizumab plus pemetrexed as maintenance treatment.
arm group label: Tislelizumab plus chemotherapy plus Bevacizumab
arm group type: Experimental
description: Tislelizumab plus Nab-paclitaxel and Bevacizumab as induction treatment and followed by Tislelizumab plus Bevacizumab as maintenance treatment.
intervention type: Drug
intervention name: Tislelizumab
description: Tislelizumab 200mg administered intravenously (IV) on Day 1 of each 21-day cycle
arm group label: Tislelizumab plus chemotherapy
arm group label: Tislelizumab plus chemotherapy plus Bevacizumab
other name: BGB-A317
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin AUC 5 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles
arm group label: Tislelizumab plus chemotherapy
intervention type: Drug
intervention name: Pemetrexed
description: Pemetrexed 500mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle
arm group label: Tislelizumab plus chemotherapy
intervention type: Drug
intervention name: Bevacizumab
description: Bevacizumab 7.5mg/kg administered intravenously (IV) on Day 1 of each 21-day cycle
arm group label: Tislelizumab plus chemotherapy plus Bevacizumab
intervention type: Drug
intervention name: Nab paclitaxel
description: Nab-paclitaxel 260mg/m2 administered intravenously (IV) on Day 1 of each 21-day cycle, 4 cycles
arm group label: Tislelizumab plus chemotherapy
arm group label: Tislelizumab plus chemotherapy plus Bevacizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Chest Hospital
investigator full name: Baohui Han
investigator title: Professor, Director of Pulmonary Medicine at Shanghai Chest Hospital
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Bevacizumab
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Tislelizumab