<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/NCT04416035</url>
  </required_header>
  <id_info>
    <org_study_id>TRS00303001</org_study_id>
    <nct_id>NCT04416035</nct_id>
  </id_info>
  <brief_title>A Study to Compare the Similarity in Efficacy and Safety Between TRS003 and China-approved Bevacizumab® in NSCLC</brief_title>
  <acronym>NSCLC</acronym>
  <official_title>A Phase 3, Multicenter, Randomized and Double-Blind Study to Assess the Similarity in Efficacy and Safety Between TRS003 and China-approved Bevacizumab in Subjects With Advanced Nonsquamous NSCLC</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Zhejiang Teruisi Pharmaceutical Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Zhejiang Teruisi Pharmaceutical Inc.</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double-blind Phase 3 clinical trial evaluating the efficacy and safety of TRS003&#xD;
      and paclitaxel-carboplatin versus China-approved bevacizumab and paclitaxel-carboplatin in&#xD;
      patients with unresectable, locally advanced, or metastatic non-squamous non-small cell lung&#xD;
      cancer (NSCLC). Approximately 608 patients will be enrolled in this study from America,&#xD;
      Europe, and Asia. Patients who sign the informed consent and meet the inclusion criteria,&#xD;
      will be randomized (1:1) to receive either TRS003 in combination with paclitaxel and&#xD;
      carboplatin or China-approved bevacizumab in combination with paclitaxel and carboplatin for&#xD;
      4 to 6 cycles.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a randomized, double-blind, multinational, multicenter, active-control, parallel&#xD;
      two-group Phase 3 clinical trial evaluating the efficacy and safety of TRS003 plus&#xD;
      paclitaxel-carboplatin versus China-approved bevacizumab plus paclitaxel-carboplatin in&#xD;
      patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC.&#xD;
      Approximately 608 subjects will be enrolled into this study from America, Europe and Asia.&#xD;
      Patients who sign the informed consent and meet the inclusion criteria will be randomized&#xD;
      (1:1) to receive either TRS003 or China-approved bevacizumab in combination with&#xD;
      paclitaxel-carboplatin for 4 to 6 cycles. Patients will be stratified by region (Asia, Europe&#xD;
      and America), gender, and cigarette smoking habit (previous smoker, smoker and non-smoker).&#xD;
&#xD;
      Patients will receive either TRS003 (Arm A), or China-approved bevacizumab (Arm B) first&#xD;
      followed by the administration of paclitaxel and carboplatin. TRS003 or China-approved&#xD;
      bevacizumab will be administered at 15 mg/kg by intravenous (IV) infusion on Day 1 of each&#xD;
      cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m^2 by IV&#xD;
      infusion (over 3 hours) Q3W on Day 1 of each cycle and carboplatin will be administered at an&#xD;
      area under the plasma concentration-time curve (AUC) 6 mg/mL/ min (the maximum dose capped at&#xD;
      900 mg) by IV infusion (over 15 - 30 minutes) Q3W on Day 1 of each cycle. Each cycle is 3&#xD;
      weeks. Treatments will continue until disease progression, death, intolerable toxicity,&#xD;
      withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy.&#xD;
      Maintenance therapy may be given at the discretion of the patient's primary oncologist.&#xD;
&#xD;
      Efficacy will be evaluated by the investigator per RECIST v1.1 (Eisenhauer et al., 2009).&#xD;
      Efficacy evaluation will be performed at baseline and every 6 weeks ± 7 days during the 4-6&#xD;
      cycle combination treatment periods. After completion of combination treatments, efficacy&#xD;
      evaluations will be performed every 9 weeks ± 7 days (if patients received maintenance&#xD;
      therapy). The analysis of Investigator-determined objective response rate (ORR) (RECIST v1.1)&#xD;
      will be based on information obtained prior to Week 19. Investigator-determined duration of&#xD;
      response (DOR) and progression-free survival (PFS) will also be evaluated according to RECIST&#xD;
      v1.1. Data on overall survival (OS) will be collected. Central radiology review will not be&#xD;
      required. However, for the purpose of quality control, the Sponsor may elect to have some or&#xD;
      all tumor assessments to be reviewed by an independent imaging vendor.&#xD;
&#xD;
      Safety will be evaluated throughout the study. Adverse events will be recorded from the time&#xD;
      of informed consent. Safety will be assessed based on periodically physical examination&#xD;
      findings, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status,&#xD;
      laboratory variables (hematology, coagulation tests, serum chemistries, urinalysis and&#xD;
      pregnancy tests), and electrocardiogram (ECG) findings. Adverse events and laboratories will&#xD;
      be graded according to National Cancer Institute (NCI) CTCAE v5.0.&#xD;
&#xD;
      Immunogenicity will be assessed in all patients who received at least one dose of TRS003 or&#xD;
      China-approved bevacizumab. Samples will be assessed for the development of antidrug&#xD;
      antibodies to either TRS003, or China-approved bevacizumab. Neutralizing antibodies (NAb)&#xD;
      will assessed in samples that are antidrug antibody (ADA) positive. Trough pharmacokinetics&#xD;
      (PK) samples will be collected and will be analyzed for interpretation of immunogenicity data&#xD;
      and exploratory analysis when needed.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 17, 2020</start_date>
  <completion_date type="Anticipated">November 10, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 21, 2021</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>ORR,Objective Response Rate</measure>
    <time_frame>19 weeks</time_frame>
    <description>Investigator-determined confirmed ORR by Week 19 per RECIST v1.1 will be determined in the intention-to-treat (ITT) population in each arm.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>PFS, Progression-free survival</measure>
    <time_frame>19 weeks</time_frame>
    <description>PFS is defined as the time from randomization to Investigator-determined progressive disease (PD) or death due to any cause in the absence of documented PD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>OS, Overall survival</measure>
    <time_frame>19 weeks</time_frame>
    <description>OS is defined as the time from randomization to death due to any cause and will be analyzed by Kaplan-Meier method.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>DOR, Duration of response</measure>
    <time_frame>19 weeks</time_frame>
    <description>DOR is defined as the time from the date of the first documentation of Investigator-determined response in patients with confirmed objective tumor response (complete response or partial response) to the first documentation of Investigator determined disease progression (PD) or to death due to any cause in the absence of documented PD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Treatment-Related Adverse Events (AEs)</measure>
    <time_frame>23 weeks</time_frame>
    <description>AEs will be assigned to preferred term using MedDRA and graded according to CTCAE v5.0.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with Immunogenicity</measure>
    <time_frame>23 weeks</time_frame>
    <description>ADA will be assessed in all patients. NAb will be assessed in samples that are ADA positive</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-inf, Area Under the Serum Concentration Versus Time Curve (Time 0 to Infinity)</measure>
    <time_frame>23 weeks</time_frame>
    <description>PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>AUC0-t, Area Under the Serum Concentration Versus Time Curve (Time 0 to t)</measure>
    <time_frame>23 weeks</time_frame>
    <description>PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax, Maximum Drug Concentration</measure>
    <time_frame>23 weeks</time_frame>
    <description>PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">608</enrollment>
  <condition>Advanced Non-squamous Non-small-cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>TRS003</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m^2 by IV infusion Q3W on Day 1 of each cycle，carboplatin will be administered at an AUC 6 mg/mL/ min by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>China-approved Bevacizumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m^2 by IV infusion Q3W on Day 1 of each cycle and carboplatin will be administered at an AUC 6 mg/mL/min (the maximum dose capped at 900 mg) by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>TRS003</intervention_name>
    <description>TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Each cycle is 3 weeks.</description>
    <arm_group_label>TRS003</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>China-approved Bevacizumab</intervention_name>
    <description>China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W).Each cycle is 3 weeks.</description>
    <arm_group_label>China-approved Bevacizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Carboplatin will be administered at an AUC 6 mg/mL/ min (the maximum dose capped at 900 mg) by IV infusion (over 15 - 30 minutes) Q3W on Day 1 of each cycle.</description>
    <arm_group_label>China-approved Bevacizumab</arm_group_label>
    <arm_group_label>TRS003</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Paclitaxel will be administered at a dose of 200 mg/m^2 by IV infusion (over 3 hours) Q3W on Day 1 of each cycle</description>
    <arm_group_label>China-approved Bevacizumab</arm_group_label>
    <arm_group_label>TRS003</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria :&#xD;
&#xD;
          1. Male or female ≥ 18 years.&#xD;
&#xD;
          2. Signed and dated informed consent form.&#xD;
&#xD;
          3. Willing and able to comply with all study procedures.&#xD;
&#xD;
          4. Histologically or cytologically confirmed unresectable, locally advanced, recurrent,&#xD;
             or metastatic nonsquamous NSCLC; if the tumor shows multiple histologies, the main&#xD;
             cellular phenotype will be used. Must provide archived tumor tissue obtained within 3&#xD;
             years for epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK)&#xD;
             testing. If archival tissue meeting this requirement is not available, patients will&#xD;
             undergo biopsy to be eligible for study entry.&#xD;
&#xD;
          5. No previous systemic therapy targeting the primary tumor or sites of metastases.&#xD;
             Adjuvant therapy should be completed at least 6 months prior to study entry. Patients&#xD;
             may have received radiation therapy if this was completed at least 1 month prior to&#xD;
             entry and if other sites of measurable disease (per RECIST v11) are present.&#xD;
&#xD;
          6. At least one measurable lesion per RECIST v1.1.&#xD;
&#xD;
          7. ECOG performance status score 0 or 1.&#xD;
&#xD;
          8. Life expectancy ≥ 6months.&#xD;
&#xD;
          9. Adequate hepatic function as evidence by meeting all the following requirements:&#xD;
&#xD;
               1. Total bilirubin ≤ 1.5 × upper limit of normal (ULN).&#xD;
&#xD;
               2. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 3×ULN or ALT ≤&#xD;
                  5 × ULN if liver metastases are present.&#xD;
&#xD;
         10. Adequate renal function as evidence by meeting all the following requirements:&#xD;
&#xD;
               1. Serum creatinine ≤ 1.5 × ULN and calculated creatinine clearance (CrCL) &gt; 50&#xD;
                  mL/min (Cockroft-Gault Equation) or estimated glomerular filtration rate (GFR) &gt;&#xD;
                  50 mL/min.&#xD;
&#xD;
               2. Urine dipstick for proteinuria &lt; 2+. If urine dipstick is greater than or equal&#xD;
                  to 2+, proteinuria must be less than 2 g in 24 hours or the urine&#xD;
                  protein/creatinine ratio &lt; 2.&#xD;
&#xD;
         11. Hematological function defined as:&#xD;
&#xD;
               1. Platelet count ≥ 100,000/μl without transfusion within 2 weeks prior to the study&#xD;
                  screening.&#xD;
&#xD;
               2. Prothrombin time, international normalized ratio or activated partial&#xD;
                  thromboplastin time &lt; 1.5 × ULN.&#xD;
&#xD;
               3. Absolute neutrophil count ≥ 1,500/μl without any medical interventional treatment&#xD;
                  within two weeks prior to the study screening (ie, granulocyte-colony stimulating&#xD;
                  factors and/or herbal remedies).&#xD;
&#xD;
               4. Hemoglobin (Hb) ≥ 9 g/dl without the need for transfusion within 2 weeks prior to&#xD;
                  the study screening.&#xD;
&#xD;
        Exclusion Criteria ：&#xD;
&#xD;
          1. Known sensitizing EGFR mutations or ALK rearrangements.&#xD;
&#xD;
          2. Squamous lung cancer, mixed small cell and non-small cell lung cancer or squamous&#xD;
             cell-dominant adeno-squamous lung cancer.&#xD;
&#xD;
          3. Tumor cavitation, invading into large blood vessels or close to large vessels (such as&#xD;
             pulmonary artery or Superior vena cava.&#xD;
&#xD;
          4. Significant thrombotic or hemorrhagic events within 6 months prior to the study&#xD;
             screening e.g., hemoptysis &gt; 2.5 mL of red blood, gastrointestinal bleeding,&#xD;
             hematemesis, central nervous system hemorrhage, severe epistaxis or vaginal bleeding,&#xD;
             etc.&#xD;
&#xD;
          5. Severe cardiovascular disease, including cerebrovascular accident (CVA), transient&#xD;
             ischemic attack (TIA), myocardial infarction and significant vascular disease&#xD;
             (including but not limited to aneurysm requiring surgical repair or recent artery&#xD;
             thrombosis); unstable angina pectoris, New York Heart Association (NYHA) class III or&#xD;
             IV heart failure and uncontrollable arrhythmia within 6 months prior to entry.&#xD;
&#xD;
          6. History of active gastroduodenal ulcer, abdominal fistula as well as&#xD;
             non-gastrointestinal fistula, gastrointestinal perforation or intra-abdominal abscess&#xD;
             within 6 months prior to the study screening.&#xD;
&#xD;
          7. Central nervous system (CNS) metastases; Subjects with asymptomatic CNS metastases who&#xD;
             are neurologically stable ≥ 4 weeks following CNS-directed therapy with no evidence of&#xD;
             CNS disease progression ≥ 4 weeks, and on a stable or decreasing dose of&#xD;
             corticosteroids may be eligible and should be discussed with the Medical Monitor.&#xD;
&#xD;
          8. Concurrent malignancy within 5 years other than adequately treated primary cervical&#xD;
             cancer, skin-squamous or basal cell carcinomas, prostatic cancer following radical&#xD;
             resection that does not require therapy, prostate cancer treated with active&#xD;
             surveillance, ductal carcinoma in situ of the breast, or &lt; T1 urothelial carcinoma.&#xD;
&#xD;
          9. Uncontrolled hypertension (systolic blood pressure &gt;150 mmHg and diastolic blood&#xD;
             pressure &gt;100 mmHg at the study screening), or a history of hypertension crisis or&#xD;
             hypertensive encephalophy.&#xD;
&#xD;
         10. Active hepatitis B or hepatitis C virus. Patients with evidence of infection with&#xD;
             hepatitis B who have an undetectable viral load are eligible for study entry. Patients&#xD;
             with evidence of infection with hepatitis C should have completed curative therapy.&#xD;
&#xD;
         11. Known to be positive for human immunodeficiency virus (HIV) and with an AIDS defining&#xD;
             opportunistic infection within 12 months of study entry or a CD4 T cell count &lt; 359&#xD;
             cells/μL.&#xD;
&#xD;
         12. Full dose anticoagulants, including oral or parenteral; Low dose anti-coagulation (not&#xD;
             intended to achieve a therapeutic INR) for port patency is permitted. No Factor Xa&#xD;
             inhibitors. No aspirin or other nonsteroidal anti-inflammatory drugs that can inhibit&#xD;
             platelet within ten days prior to screening. No history of hemorrhagic or thrombotic&#xD;
             disorders (e.g., hemophilia, protein C deficiency).&#xD;
&#xD;
         13. Thoracic radiotherapy within 4 weeks prior to screening or palliative radiotherapy for&#xD;
             metastasis outside thoracic region within 2 weeks prior to screening.&#xD;
&#xD;
         14. Any major surgical procedure within 28 days prior to screening or anticipated elective&#xD;
             surgery during the study. Any minor surgery such as deep vein catheterization within&#xD;
             48 hours prior to the first dose of the study drugs.&#xD;
&#xD;
         15. Evidence of pericardial or pleural effusion or ascites that requires intervention.&#xD;
&#xD;
         16. Treatment history of monoclonal antibodies or small molecule inhibitors against&#xD;
             vascular endothelial growth factor (VEGF) or its receptor (VEGFR), including&#xD;
             bevacizumab.&#xD;
&#xD;
         17. Clinically uncontrolled active infection requiring systemic therapy within 2 weeks&#xD;
             prior to entry.&#xD;
&#xD;
         18. Subject has known sensitivity to any of the products to be administered during the&#xD;
             study, including mammalian cell derived drug products.&#xD;
&#xD;
         19. Participation in any other clinical trial within 4 weeks prior to screening. Recipient&#xD;
             of any anticancer therapy (other than hormones used to treat breast cancer) within 4&#xD;
             weeks prior to screening.&#xD;
&#xD;
         20. Women of childbearing potential who are pregnant or is breast feeding or who do not&#xD;
             consent to use highly effective methods of birth control during treatment and for an&#xD;
             additional 120 days after the last administration of the protocol specified treatment.&#xD;
&#xD;
         21. Men with a partner of childbearing potential who does not consent to use highly&#xD;
             effective methods of birth control during treatment and for an additional 120 days&#xD;
             after the last administration of the protocol specified treatment.&#xD;
&#xD;
         22. Any condition that the Investigator or primary physician believes may not be&#xD;
             appropriate for participating the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Yuankai Shi, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Cancer Institute and Hospital, Chinese Academy of Medical Sciences</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yilin Li</last_name>
    <phone>(+86)5722126820</phone>
    <email>yilin.li@teruisipharm.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Anhui Provincial Center Hospital</name>
      <address>
        <city>Hefei</city>
        <state>Anhui</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Changlu Hu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Chinese Academy of Medical Sciences, Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100021</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yuankai Shi, MD</last_name>
      <phone>13701251865</phone>
    </contact>
  </location>
  <location>
    <facility>
      <name>Beijing Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yanming Li</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Xingtai Medical College</name>
      <address>
        <city>Xingtai</city>
        <state>Hebei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kaoshan Guo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Wuhan Fourth Hospital</name>
      <address>
        <city>Wuhan</city>
        <state>Hubei</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gang Feng</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Second Affiliated Hospital of Suzhou University</name>
      <address>
        <city>Suzhou</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhixiang Zhuang</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>FAW General Hospital of Jilin Province</name>
      <address>
        <city>Changchun</city>
        <state>Jilin</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Libo Liu</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Jinan Central Hospital</name>
      <address>
        <city>Jinan</city>
        <state>Shandong</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chunyan Xing</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shanghai East Hospital</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhongliang Guo</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shanghai Fifth People's Hospital, Fudan University</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhijun Jie</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>Nanchong Central Hospital</name>
      <address>
        <city>Nanchong</city>
        <state>Sichuan</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xin Hu</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>June 1, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 4, 2020</study_first_posted>
  <last_update_submitted>August 27, 2020</last_update_submitted>
  <last_update_submitted_qc>August 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 31, 2020</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>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>
  </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/NCT04416035
org study id: TRS00303001
nct id: NCT04416035
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a double-blind Phase 3 clinical trial evaluating the efficacy and safety of TRS003
      and paclitaxel-carboplatin versus China-approved bevacizumab and paclitaxel-carboplatin in
      patients with unresectable, locally advanced, or metastatic non-squamous non-small cell lung
      cancer (NSCLC). Approximately 608 patients will be enrolled in this study from America,
      Europe, and Asia. Patients who sign the informed consent and meet the inclusion criteria,
      will be randomized (1:1) to receive either TRS003 in combination with paclitaxel and
      carboplatin or China-approved bevacizumab in combination with paclitaxel and carboplatin for
      4 to 6 cycles.
This is a randomized, double-blind, multinational, multicenter, active-control, parallel
      two-group Phase 3 clinical trial evaluating the efficacy and safety of TRS003 plus
      paclitaxel-carboplatin versus China-approved bevacizumab plus paclitaxel-carboplatin in
      patients with unresectable, locally advanced, recurrent or metastatic non-squamous NSCLC.
      Approximately 608 subjects will be enrolled into this study from America, Europe and Asia.
      Patients who sign the informed consent and meet the inclusion criteria will be randomized
      (1:1) to receive either TRS003 or China-approved bevacizumab in combination with
      paclitaxel-carboplatin for 4 to 6 cycles. Patients will be stratified by region (Asia, Europe
      and America), gender, and cigarette smoking habit (previous smoker, smoker and non-smoker).

      Patients will receive either TRS003 (Arm A), or China-approved bevacizumab (Arm B) first
      followed by the administration of paclitaxel and carboplatin. TRS003 or China-approved
      bevacizumab will be administered at 15 mg/kg by intravenous (IV) infusion on Day 1 of each
      cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m^2 by IV
      infusion (over 3 hours) Q3W on Day 1 of each cycle and carboplatin will be administered at an
      area under the plasma concentration-time curve (AUC) 6 mg/mL/ min (the maximum dose capped at
      900 mg) by IV infusion (over 15 - 30 minutes) Q3W on Day 1 of each cycle. Each cycle is 3
      weeks. Treatments will continue until disease progression, death, intolerable toxicity,
      withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy.
      Maintenance therapy may be given at the discretion of the patient's primary oncologist.

      Efficacy will be evaluated by the investigator per RECIST v1.1 (Eisenhauer et al., 2009).
      Efficacy evaluation will be performed at baseline and every 6 weeks ± 7 days during the 4-6
      cycle combination treatment periods. After completion of combination treatments, efficacy
      evaluations will be performed every 9 weeks ± 7 days (if patients received maintenance
      therapy). The analysis of Investigator-determined objective response rate (ORR) (RECIST v1.1)
      will be based on information obtained prior to Week 19. Investigator-determined duration of
      response (DOR) and progression-free survival (PFS) will also be evaluated according to RECIST
      v1.1. Data on overall survival (OS) will be collected. Central radiology review will not be
      required. However, for the purpose of quality control, the Sponsor may elect to have some or
      all tumor assessments to be reviewed by an independent imaging vendor.

      Safety will be evaluated throughout the study. Adverse events will be recorded from the time
      of informed consent. Safety will be assessed based on periodically physical examination
      findings, vital signs, Eastern Cooperative Oncology Group (ECOG) performance status,
      laboratory variables (hematology, coagulation tests, serum chemistries, urinalysis and
      pregnancy tests), and electrocardiogram (ECG) findings. Adverse events and laboratories will
      be graded according to National Cancer Institute (NCI) CTCAE v5.0.

      Immunogenicity will be assessed in all patients who received at least one dose of TRS003 or
      China-approved bevacizumab. Samples will be assessed for the development of antidrug
      antibodies to either TRS003, or China-approved bevacizumab. Neutralizing antibodies (NAb)
      will assessed in samples that are antidrug antibody (ADA) positive. Trough pharmacokinetics
      (PK) samples will be collected and will be analyzed for interpretation of immunogenicity data
      and exploratory analysis when needed.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: ORR,Objective Response Rate
time frame: 19 weeks
description: Investigator-determined confirmed ORR by Week 19 per RECIST v1.1 will be determined in the intention-to-treat (ITT) population in each arm.
measure: PFS, Progression-free survival
time frame: 19 weeks
description: PFS is defined as the time from randomization to Investigator-determined progressive disease (PD) or death due to any cause in the absence of documented PD.
measure: OS, Overall survival
time frame: 19 weeks
description: OS is defined as the time from randomization to death due to any cause and will be analyzed by Kaplan-Meier method.
measure: DOR, Duration of response
time frame: 19 weeks
description: DOR is defined as the time from the date of the first documentation of Investigator-determined response in patients with confirmed objective tumor response (complete response or partial response) to the first documentation of Investigator determined disease progression (PD) or to death due to any cause in the absence of documented PD.
measure: Number of Participants with Treatment-Related Adverse Events (AEs)
time frame: 23 weeks
description: AEs will be assigned to preferred term using MedDRA and graded according to CTCAE v5.0.
measure: Number of Participants with Immunogenicity
time frame: 23 weeks
description: ADA will be assessed in all patients. NAb will be assessed in samples that are ADA positive
measure: AUC0-inf, Area Under the Serum Concentration Versus Time Curve (Time 0 to Infinity)
time frame: 23 weeks
description: PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
measure: AUC0-t, Area Under the Serum Concentration Versus Time Curve (Time 0 to t)
time frame: 23 weeks
description: PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
measure: Cmax, Maximum Drug Concentration
time frame: 23 weeks
description: PK will only be analyzed for interpretation of immunogenicity data and exploratory analysis when needed.
arm group label: TRS003
arm group type: Experimental
description: TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m^2 by IV infusion Q3W on Day 1 of each cycle，carboplatin will be administered at an AUC 6 mg/mL/ min by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist.
arm group label: China-approved Bevacizumab
arm group type: Active Comparator
description: China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Paclitaxel will be administered at a dose of 200 mg/m^2 by IV infusion Q3W on Day 1 of each cycle and carboplatin will be administered at an AUC 6 mg/mL/min (the maximum dose capped at 900 mg) by IV infusion Q3W on Day 1 of each cycle. Each cycle is 3 weeks. Treatments will continue until disease progression, death, intolerable toxicity, withdrawal of consent, investigator decision, or completion of 4-6 cycles of therapy. Maintenance therapy may be given at the discretion of the patient's primary oncologist.
intervention type: Biological
intervention name: TRS003
description: TRS003 will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W). Each cycle is 3 weeks.
arm group label: TRS003
intervention type: Biological
intervention name: China-approved Bevacizumab
description: China-approved bevacizumab will be administered at 15 mg/kg by IV infusion on Day 1 of each cycle (every 3 weeks, Q3W).Each cycle is 3 weeks.
arm group label: China-approved Bevacizumab
intervention type: Drug
intervention name: Carboplatin
description: Carboplatin will be administered at an AUC 6 mg/mL/ min (the maximum dose capped at 900 mg) by IV infusion (over 15 - 30 minutes) Q3W on Day 1 of each cycle.
arm group label: China-approved Bevacizumab
arm group label: TRS003
intervention type: Drug
intervention name: Paclitaxel
description: Paclitaxel will be administered at a dose of 200 mg/m^2 by IV infusion (over 3 hours) Q3W on Day 1 of each cycle
arm group label: China-approved Bevacizumab
arm group label: TRS003
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yuankai Shi, MD
role: Principal Investigator
affiliation: Cancer Institute and Hospital, Chinese Academy of Medical Sciences
last name: Yilin Li
phone: (+86)5722126820
email: yilin.li@teruisipharm.com
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country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Bevacizumab
mesh term: Carboplatin