<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/NCT04459611</url>
  </required_header>
  <id_info>
    <org_study_id>2020-KYY-518052-0092</org_study_id>
    <nct_id>NCT04459611</nct_id>
  </id_info>
  <brief_title>Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）</brief_title>
  <acronym>neoSCORE</acronym>
  <official_title>Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）：A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Second Affiliated Hospital, School of Medicine, Zhejiang University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Second Affiliated Hospital, School of Medicine, Zhejiang University</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 2, prospective, randomized, open-Label, single-center international study&#xD;
      that assesses the efficacy and safety of neoadjuvant therapy with different cycles of&#xD;
      sintilimab combined with chemotherapy for resectable NSCLC. This trial will also explore the&#xD;
      biomarkers of neoadjuvant immunochemotherapy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 2, prospective, randomized, open-Label, single-center international study&#xD;
      that assesses the efficacy and safety of neoadjuvant therapy with different cycles of&#xD;
      sintilimab combined with chemotherapy for resectable NSCLC. In this trial, eligible subjects&#xD;
      will be randomly assigned to arm A and arm B (1:1). Subjects in arm A will receive 2 cycles&#xD;
      of neoadjuvant chemotherapy with sintilimab + chemotherapy and arm B will receive 3 cycles of&#xD;
      neoadjuvant chemotherapy with sintilimab + chemotherapy, followed by surgery within the 4th&#xD;
      week after the last dose of sintilimab. After operation, subjects in arm A will receive 2&#xD;
      cycles of adjuvant chemotherapy and arm B will receive 1 cycle of adjuvant chemotherapy,&#xD;
      followed by the maintenance treatment of sintilimab for up to 1 year according to the&#xD;
      requirements of patients. The primary purpose is MPR rate of neoadjuvant chemotherapy of&#xD;
      resectable NSCLC with different cycles of sintilimab combined with platinum-based&#xD;
      chemotherapy, which is defined as the percentage of participants having ≤10% viable tumor&#xD;
      cells in the pathological examination of resected specimens.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">July 1, 2023</completion_date>
  <primary_completion_date type="Actual">November 1, 2021</primary_completion_date>
  <phase>Phase 2</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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Major pathological response rate (MPR)</measure>
    <time_frame>At time of surgery</time_frame>
    <description>MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Pathology complete response rate(pCR)</measure>
    <time_frame>At time of surgery</time_frame>
    <description>pCR rate is defined as the percentage of participants lacking of evidence of viable tumor cells in the pathological examination of resected specimens.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>prior to surgery</time_frame>
    <description>ORR is defined as the percentage of participants having a complete response or a partial response, measured by RECIST 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2 years disease-free survival rate (DFS)</measure>
    <time_frame>2 years postoperatively</time_frame>
    <description>2 years DFS rate is defined as the percentage of participants having no recurrence, distant metastasis or death within 2 years after operation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>2 years overall survival rate (OS)</measure>
    <time_frame>2 years postoperatively</time_frame>
    <description>2 years OS rate is defined as the percentage of participants having no death of any cause within 2 years after operation.The Kaplan-Meier estimator will be used to estimate median OS and its 95%CI and the survival curve.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>sintilimab</intervention_name>
    <description>200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.</description>
    <arm_group_label>sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <arm_group_label>sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <other_name>IBI308</other_name>
    <other_name>PD-1 antibody</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pemetrexed</intervention_name>
    <description>500 mg/m^2 by IV infusion Q3W, given on cycle day 1.</description>
    <arm_group_label>sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <arm_group_label>sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>AUC 5 mg/mL/min by IV infusion Q3W, given on cycle day 1.</description>
    <arm_group_label>sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <arm_group_label>sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>albumin-bound paclitaxel</intervention_name>
    <description>260 mg/m^2 by IV infusion Q3W, given on cycle day 1.</description>
    <arm_group_label>sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)</arm_group_label>
    <arm_group_label>sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Sign the informed consent form before starting any trial related procedure.&#xD;
&#xD;
          -  18-75 years old, male or female.&#xD;
&#xD;
          -  Non-small cell lung cancer confirmed by cytology or histology.&#xD;
&#xD;
          -  There must be at least one evaluable focus judged according to recist1.1 standard.&#xD;
&#xD;
          -  Evaluation by the researchers to confirm resectable stage cⅠb-Ⅲa NSCLC patients&#xD;
             without any treatment before.&#xD;
&#xD;
          -  ECOG PS 0-1.&#xD;
&#xD;
          -  Life expectancy &gt; 6 months.&#xD;
&#xD;
          -  Adequate organ function and it should meet the following criteria:&#xD;
&#xD;
               1. No use of Granulocyte colony stimulating factor within 14 days, absolute&#xD;
                  neutrophils count(ANC)≥1.5x109/L, platelets count(PLT)&gt;9g/dL,&#xD;
                  hemoglobin(HB)≥100×109/L;&#xD;
&#xD;
               2. Total bilirubin(TBIL)≤1.5ULN, ALT、AST≤ 2.5 ULN, serum creatinine(sCr)≤1.5ULN;&#xD;
&#xD;
               3. good blood coagulation: INR≤1.5 or PT≤1.5 ULN;&#xD;
&#xD;
               4. normal thyroid function: TSH within normal institutional limits;&#xD;
&#xD;
          -  Women of childbearing age must undergo a serological pregnancy test within 3 days&#xD;
             before the first dose(cycle 1 day 1) with negative results. If the result of urine&#xD;
             pregnancy test cannot be confirmed as negative, blood pregnancy test is required.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Malignancies within 5 years prior to the first dose(excluding radical skin basal cell&#xD;
             carcinoma, skin squamous cell carcinoma and / or radical resection of carcinoma in&#xD;
             situ).&#xD;
&#xD;
          -  Currently participating in the intervention clinical treatment, or receiving other&#xD;
             drugs or research instruments within 4 weeks before the first dose.&#xD;
&#xD;
          -  Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or&#xD;
             drugs for another stimulation or synergistic inhibition of T cell receptor (e.g.&#xD;
             CTLA-4, OX-40, CD137).&#xD;
&#xD;
          -  Active autoimmune diseases requiring systemic treatment (e.g. using disease improving&#xD;
             drugs, corticosteroids or immunosuppressants) occurred within 2 years before the first&#xD;
             dose. Alternative therapies (e.g. thyroxine, insulin or corticosteroids in&#xD;
             physiological doses for adrenal or pituitary insufficiency) are not considered&#xD;
             systemic treatment.&#xD;
&#xD;
          -  Systemic glucocorticoid therapy (excluding local glucocorticoids by nasal spray,&#xD;
             inhalation or other routes) or any other form of immunosuppressive therapy is in&#xD;
             progress within 7 days before the first dose.&#xD;
&#xD;
        Note: it is allowed to use physiological dose of glucocorticoid (Prednisone≤10 mg/d or&#xD;
        equivalent drug).&#xD;
&#xD;
          -  Received allogeneic organ transplantation (except corneal transplantation) or&#xD;
             allogeneic hematopoietic stem cell transplantation.&#xD;
&#xD;
          -  Allergic to study drug(sintilimab, pemetrexed, carboplatin, albumin-bound paclitaxel)&#xD;
             components excipients.&#xD;
&#xD;
          -  Not fully recovered from toxicity and/or complications caused by any intervention&#xD;
             before treatment (≤level 1 or reach baseline, excluding fatigue or hair loss).&#xD;
&#xD;
          -  Has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibody&#xD;
             positive).&#xD;
&#xD;
          -  Untreated active Hepatitis B (defined as HBsAg positive and HBV-DNA copies&gt;ULN).&#xD;
&#xD;
          -  Active Hepatitis C (HCV antibody positive and HCV-RNA level higher than the detection&#xD;
             limit).&#xD;
&#xD;
          -  Inoculate the live vaccine within 30 days before the first dose (cycle 1 day 1).&#xD;
&#xD;
        Note: it is allowed to receive the injection inactivated virus vaccine for seasonal&#xD;
        influenza within 30 days before the first dose; however, it is not allowed to accept the&#xD;
        live attenuated influenza vaccine for intranasal medication.&#xD;
&#xD;
          -  Pregnant or lactating women.&#xD;
&#xD;
          -  There are any serious or uncontrollable systemic diseases, such as:&#xD;
&#xD;
               1. Resting ECG has significant abnormalities in rhythm, conduction or morphology,&#xD;
                  and the symptoms are serious and difficult to control,such as complete left&#xD;
                  bundle branch block, heart block above degree Ⅱ, ventricular arrhythmia or atrial&#xD;
                  fibrillation;&#xD;
&#xD;
               2. Unstable angina, congestive heart failure, chronic heart failure with NYHA grade&#xD;
                  ≥ 2;&#xD;
&#xD;
               3. Within 6 months before inclusion, there were any arterial thrombosis, embolism or&#xD;
                  ischemia, such as myocardial infarction, unstable angina, cerebrovascular&#xD;
                  accident, transient ischemic attack etc;&#xD;
&#xD;
               4. History of noninfectious pneumonia requiring glucocorticoid treatment within 1&#xD;
                  year before the first dose,or having currently clinical active interstitial lung&#xD;
                  diseases;&#xD;
&#xD;
               5. Active pulmonary tuberculosis;&#xD;
&#xD;
               6. Active or uncontrolled infections requiring systemic treatment;&#xD;
&#xD;
               7. Liver diseases such as cirrhosis, decompensated liver disease, acute or chronic&#xD;
                  active hepatitis;&#xD;
&#xD;
               8. poorly controlled diabetes (Fasting blood glucose (FBG)&gt;10mmol/L);&#xD;
&#xD;
               9. Urine routine test indicates that urine protein≥++, and confirmed that 24 hours&#xD;
                  proteinuria&gt;1.0 g;&#xD;
&#xD;
              10. Patients with mental disorders who are unable to cooperate with the treatment;&#xD;
&#xD;
          -  There are medical history, disease, treatment or laboratory abnormal results that may&#xD;
             interfere with the test results, prevent the subjects from participating in the whole&#xD;
             process of the study, or the researchers think that participating in the study is not&#xD;
             in the best interests of the subjects or there are other potential risks that the&#xD;
             subjects are not suitable for the study.&#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>Second Affiliated Hospital, School of Medicine, Zhejiang University</name>
      <address>
        <city>Hangzhou</city>
        <state>Zhejiang</state>
        <zip>310009</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 2, 2020</study_first_submitted>
  <study_first_submitted_qc>July 2, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>July 11, 2022</last_update_submitted>
  <last_update_submitted_qc>July 11, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">July 12, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>sintilimab</keyword>
  <keyword>resectable NSCLC</keyword>
  <keyword>neoadjuvant immunochemotherapy</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>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Albumin-Bound Paclitaxel</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/NCT04459611
org study id: 2020-KYY-518052-0092
nct id: NCT04459611
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a Phase 2, prospective, randomized, open-Label, single-center international study
      that assesses the efficacy and safety of neoadjuvant therapy with different cycles of
      sintilimab combined with chemotherapy for resectable NSCLC. This trial will also explore the
      biomarkers of neoadjuvant immunochemotherapy.
This is a Phase 2, prospective, randomized, open-Label, single-center international study
      that assesses the efficacy and safety of neoadjuvant therapy with different cycles of
      sintilimab combined with chemotherapy for resectable NSCLC. In this trial, eligible subjects
      will be randomly assigned to arm A and arm B (1:1). Subjects in arm A will receive 2 cycles
      of neoadjuvant chemotherapy with sintilimab + chemotherapy and arm B will receive 3 cycles of
      neoadjuvant chemotherapy with sintilimab + chemotherapy, followed by surgery within the 4th
      week after the last dose of sintilimab. After operation, subjects in arm A will receive 2
      cycles of adjuvant chemotherapy and arm B will receive 1 cycle of adjuvant chemotherapy,
      followed by the maintenance treatment of sintilimab for up to 1 year according to the
      requirements of patients. The primary purpose is MPR rate of neoadjuvant chemotherapy of
      resectable NSCLC with different cycles of sintilimab combined with platinum-based
      chemotherapy, which is defined as the percentage of participants having ≤10% viable tumor
      cells in the pathological examination of resected specimens.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Major pathological response rate (MPR)
time frame: At time of surgery
description: MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.
measure: Pathology complete response rate(pCR)
time frame: At time of surgery
description: pCR rate is defined as the percentage of participants lacking of evidence of viable tumor cells in the pathological examination of resected specimens.
measure: Objective response rate (ORR)
time frame: prior to surgery
description: ORR is defined as the percentage of participants having a complete response or a partial response, measured by RECIST 1.1.
measure: 2 years disease-free survival rate (DFS)
time frame: 2 years postoperatively
description: 2 years DFS rate is defined as the percentage of participants having no recurrence, distant metastasis or death within 2 years after operation.
measure: 2 years overall survival rate (OS)
time frame: 2 years postoperatively
description: 2 years OS rate is defined as the percentage of participants having no death of any cause within 2 years after operation.The Kaplan-Meier estimator will be used to estimate median OS and its 95%CI and the survival curve.
arm group label: sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
arm group type: Experimental
description: Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
arm group label: sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
arm group type: Experimental
description: Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
intervention type: Biological
intervention name: sintilimab
description: 200 mg by IV infusion every 3 weeks (Q3W), given on cycle day 1.
arm group label: sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
arm group label: sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
other name: IBI308
other name: PD-1 antibody
intervention type: Drug
intervention name: pemetrexed
description: 500 mg/m^2 by IV infusion Q3W, given on cycle day 1.
arm group label: sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
arm group label: sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
intervention type: Drug
intervention name: Carboplatin
description: AUC 5 mg/mL/min by IV infusion Q3W, given on cycle day 1.
arm group label: sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
arm group label: sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
intervention type: Drug
intervention name: albumin-bound paclitaxel
description: 260 mg/m^2 by IV infusion Q3W, given on cycle day 1.
arm group label: sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
arm group label: sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
country: China
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Albumin-Bound Paclitaxel