xml: <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/NCT05962021</url>
    </required_header>
    <id_info>
      <org_study_id>JS001-ISS-CO413</org_study_id>
      <nct_id>NCT05962021</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Toripalimab for Non-squamous NSCLC With EGFR Mutation</brief_title>
    <official_title>Neoadjuvant Toripalimab Plus Chemotherapy for Resectable Stage II-IIIB Non-squamous Non-small Cell Lung Cancer With EGFR Mutation: a Multicentre, Multi-cohort, Exploratory Study.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Peking University People's Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Shanghai Junshi Bioscience Co., Ltd.</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Peking University People's 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>
    </oversight_info>
    <brief_summary>
      <textblock>
        This study was designed to investigate the efficacy and safety of neoadjuvant Toripalimab&#xD;
        (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous NSCLC&#xD;
        harboring EGFR mutation, and to explore the potential predictive and prognostic biomarkers,&#xD;
        aiming to provide more abundant evidences for the preoperative treatment decision of&#xD;
        non-squamous NSCLC patients.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Previous studies have confirmed the efficacy of neoadjuvant immunotherapy in NSCLC patients&#xD;
        without driver gene mutation, while its efficacy in driver gene mutated patients is still&#xD;
        controversial. This study was designed to investigate the efficacy and safety of neoadjuvant&#xD;
        Toripalimab (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous&#xD;
        NSCLC harboring EGFR mutation, and to explore the potential predictive and prognostic&#xD;
        biomarkers, aiming to provide more abundant evidences for the preoperative treatment decision&#xD;
        of non-squamous NSCLC patients.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 1, 2023</start_date>
    <completion_date type="Anticipated">June 30, 2026</completion_date>
    <primary_completion_date type="Anticipated">June 30, 2026</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>
      <intervention_model_description>Patients were divided into the 19del and L858R groups according to their EGFR mutation status.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Pathologic Complete Response (pCR) Rate</measure>
      <time_frame>Within 1 week after surgery</time_frame>
      <description>Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Major Pathologic Response (MPR) Rate</measure>
      <time_frame>Within 1 week after surgery</time_frame>
      <description>Major pathologic response (MPR) rate is defined as the percentage of participants with less than or equal to 10% of residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different EGFR mutations status</measure>
      <time_frame>Within 1 week after surgery</time_frame>
      <description>Assessing pCR rates in the 19del and L858R groups separately.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different EGFR mutations status</measure>
      <time_frame>Within 1 week after surgery</time_frame>
      <description>Assessing MRP rates in the 19del and L858R groups separately.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different PD-L1 expression levels</measure>
      <time_frame>Within 1 week after surgery</time_frame>
      <description>Assessing pCR rates in the PD-L1 TPS≥1% and PD-L1 TPS&lt;1% groups separately.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different PD-L1 expression levels</measure>
      <time_frame>Within 1 week after surgery</time_frame>
      <description>Assessing MRP rates in the PD-L1 TPS≥1% and PD-L1 TPS&lt;1% groups separately.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Event-free Survival (EFS)</measure>
      <time_frame>Up to 24 months after participation</time_frame>
      <description>EFS is defined as the time from participation to any of the following events: progression of disease, recurrence disease, or death due to any cause. Progression/recurrence will be assessed either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>The Safety and Tolerability</measure>
      <time_frame>Up to 24 months after participation</time_frame>
      <description>To assess the safety and tolerability of neoadjuvant immuno-chemotherapy in patients with resectable stage II-IIIB non-squamous non-small cell lung cancer harboring EGFR mutations, including as follows: number, frequency and proportion of patients with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) and on-study deaths.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">126</enrollment>
    <condition>Non Squamous Non Small Cell Lung Cancer</condition>
    <condition>EGFR Positive Non-small Cell Lung Cancer</condition>
    <arm_group>
      <arm_group_label>19DEL cohort</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients who participated in the trial with EGFR 19DEL mutation will be included in this arm.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>L858R cohort</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients who participated in the trial with EGFR L858R mutation will be included in this arm</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Toripalimab plus Chemotherapy</intervention_name>
      <description>Therapy was administered on a 21-day regimen for 3 cycles, with Toripalimab (240mg, d1), carboplatin (AUC=5, d1) + pemetrexed (500 mg/m2, d1) for patients with lung adenocarcinoma and carboplatin (AUC=5, d1) + albumin-bound paclitaxel (260 mg/m2, d1) for patients with other subtypes.</description>
      <arm_group_label>19DEL cohort</arm_group_label>
      <arm_group_label>L858R cohort</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Provision of signed informed consent by the patient or legally acceptable&#xD;
               representative;&#xD;
  &#xD;
            2. Previously untreated, histologically confirmed resectable stage II-IIIA, IIIB(N2)&#xD;
               (AJCC staging 8th edition) non-squamous non-small cell lung cancer;&#xD;
  &#xD;
            3. Adequate tissue samples for PD-L1 immunohistochemical testing and gene mutations test&#xD;
               by RT-pCR or NGS, or consent for blood RT-PCR or NGS if tissue samples are&#xD;
               insufficient;&#xD;
  &#xD;
            4. Harboring EGFR mutation (19del or L858R);&#xD;
  &#xD;
            5. Aged 18-70 years, regardless of gender;&#xD;
  &#xD;
            6. Eastern Cooperative Group (ECOG) Performance Status 0-1;&#xD;
  &#xD;
            7. Acceptable cardiac function with a left ventricular ejection fraction &gt;50%;&#xD;
  &#xD;
            8. Acceptable respiratory function (FEV1&gt;1.5L, DLCO&gt;50%) and ability to tolerate radical&#xD;
               lung cancer surgery;&#xD;
  &#xD;
            9. Acceptable bone marrow haematopoiesis with leucocytes ≥ 4 x 10^9/L, neutrophils ≥ 1.5&#xD;
               x 10^9/L, haemoglobin ≥ 10g/dL and platelets ≥ 100 x 10^9/L;&#xD;
  &#xD;
           10. Acceptable renal function with a glomerular filtration rate ≥ 60 mL/min;&#xD;
  &#xD;
           11. Acceptable liver function with total bilirubin ≤ 1.5 x ULN, AST ≤ 3 x ULN, and ALT ≤ 3&#xD;
               x ULN;&#xD;
  &#xD;
           12. Presence of measurable lesions as defined by RECIST 1.1 criteria;&#xD;
  &#xD;
           13. Women of childbearing potential must have a negative serum or urine pregnancy test&#xD;
               (minimum sensitivity 25 IU/L or equivalent units of HCG) within 3 days prior to the&#xD;
               start of study treatment, and agree to use effective contraception for the duration of&#xD;
               study drug use and for 120 days after the last dose. Women of childbearing potential&#xD;
               were defined as sexually mature females who 1) had not undergone hysterectomy or&#xD;
               bilateral oophorectomy and 2) had not experienced spontaneous menopause for 12&#xD;
               consecutive months (amenorrhea after cancer treatment did not preclude fertility)&#xD;
               (menstruation had occurred at any time during the previous 12 consecutive months).&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Pathological histologically confirmed small cell lung cancer, squamous epithelial cell&#xD;
               carcinoma and other pathological subtypes cannot be enrolled;&#xD;
  &#xD;
            2. Patients with advanced or metastatic lung cancer, or unresectable lung cancer, or who&#xD;
               have received previous systemic anti-tumour therapy such as immunotherapy,&#xD;
               chemotherapy or targeted therapy cannot be enrolled;&#xD;
  &#xD;
            3. Patients with a history of active autoimmune disease or autoimmune disease that is&#xD;
               likely to recur cannot be enrolled;&#xD;
  &#xD;
            4. Patients with active hepatitis B and C requiring relevant antiviral therapy need to&#xD;
               have HBV-DNA &lt;500 IU/ml and have been on anti-HBV treatment for at least 14 days prior&#xD;
               to study entry and continue treatment during the treatment period; HCV RNA-positive&#xD;
               patients should be excluded;&#xD;
  &#xD;
            5. Patients who are allergic to chemotherapeutic agents such as carboplatin, paclitaxel,&#xD;
               albumin paclitaxel, pemetrexed;&#xD;
  &#xD;
            6. Patients with a history of allergy to monoclonal antibody drugs;&#xD;
  &#xD;
            7. Patients who have previously received an allogeneic stem cell transplant or organ&#xD;
               transplant；&#xD;
  &#xD;
            8. Patients with mental illness or any other illness that makes it impossible to comply&#xD;
               with treatment；&#xD;
  &#xD;
            9. Patients who are unable or unwilling to sign the informed consent form；&#xD;
  &#xD;
           10. Patients with comorbidities or other conditions that, in the opinion of the&#xD;
               investigator, may affect compliance with the protocol or make them unsuitable for&#xD;
               participation in this study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>17 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Fan Yanf, M.D.</last_name>
      <role>Study Chair</role>
      <affiliation>Peking University People's Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Fan Yang, M.D.</last_name>
      <phone>+86-010-88326657</phone>
      <email>yangfan@pkuph.edu.cn</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Xiang Yan, M.D.</last_name>
      <phone>+86-13581786750</phone>
      <email>yxiang301@sina.com</email>
    </overall_contact_backup>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>July 18, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 27, 2023</study_first_posted>
    <last_update_submitted>July 28, 2023</last_update_submitted>
    <last_update_submitted_qc>July 28, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 1, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Peking University People's Hospital</investigator_affiliation>
      <investigator_full_name>Yang Fan, MD</investigator_full_name>
      <investigator_title>Professor of Thoracic Surgery</investigator_title>
    </responsible_party>
    <keyword>Non squamous non small cell lung cancer</keyword>
    <keyword>EGFR Mutation</keyword>
    <keyword>Neoadjuvant immuno-chemotherapy</keyword>
    <keyword>Predictive and prognostic biomarker</keyword>
    <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>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05962021
  org study id: JS001-ISS-CO413
  nct id: NCT05962021
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This study was designed to investigate the efficacy and safety of neoadjuvant Toripalimab
        (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous NSCLC
        harboring EGFR mutation, and to explore the potential predictive and prognostic biomarkers,
        aiming to provide more abundant evidences for the preoperative treatment decision of
        non-squamous NSCLC patients.
  Previous studies have confirmed the efficacy of neoadjuvant immunotherapy in NSCLC patients
        without driver gene mutation, while its efficacy in driver gene mutated patients is still
        controversial. This study was designed to investigate the efficacy and safety of neoadjuvant
        Toripalimab (anti-PD1) plus chemotherapy for patients with resectable II-IIIB non-squamous
        NSCLC harboring EGFR mutation, and to explore the potential predictive and prognostic
        biomarkers, aiming to provide more abundant evidences for the preoperative treatment decision
        of non-squamous NSCLC patients.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Patients were divided into the 19del and L858R groups according to their EGFR mutation status.
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Pathologic Complete Response (pCR) Rate
  time frame: Within 1 week after surgery
  description: Pathologic complete response (pCR) rate is defined as the percentage of participants with no residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR).
  measure: Major Pathologic Response (MPR) Rate
  time frame: Within 1 week after surgery
  description: Major pathologic response (MPR) rate is defined as the percentage of participants with less than or equal to 10% of residual viable tumor in lung primary or lymph nodes as evaluated by blinded independent pathological review (BIPR). Viable tumors in situ carcinoma should not be included in MPR calculation.
  measure: Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different EGFR mutations status
  time frame: Within 1 week after surgery
  description: Assessing pCR rates in the 19del and L858R groups separately.
  measure: Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different EGFR mutations status
  time frame: Within 1 week after surgery
  description: Assessing MRP rates in the 19del and L858R groups separately.
  measure: Pathologic Complete Response (pCR) Rate in non-squamous NSCLC with different PD-L1 expression levels
  time frame: Within 1 week after surgery
  description: Assessing pCR rates in the PD-L1 TPS≥1% and PD-L1 TPS<1% groups separately.
  measure: Major Pathologic Response (MPR) Rate in non-squamous NSCLC with different PD-L1 expression levels
  time frame: Within 1 week after surgery
  description: Assessing MRP rates in the PD-L1 TPS≥1% and PD-L1 TPS<1% groups separately.
  measure: Event-free Survival (EFS)
  time frame: Up to 24 months after participation
  description: EFS is defined as the time from participation to any of the following events: progression of disease, recurrence disease, or death due to any cause. Progression/recurrence will be assessed either by biopsy assessed by local pathologist or by investigator-assessed imaging using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  measure: The Safety and Tolerability
  time frame: Up to 24 months after participation
  description: To assess the safety and tolerability of neoadjuvant immuno-chemotherapy in patients with resectable stage II-IIIB non-squamous non-small cell lung cancer harboring EGFR mutations, including as follows: number, frequency and proportion of patients with adverse events (AEs), serious adverse events (SAEs) and AEs of special interest (AESI) and on-study deaths.
  arm group label: 19DEL cohort
  arm group type: Experimental
  description: Patients who participated in the trial with EGFR 19DEL mutation will be included in this arm.
  arm group label: L858R cohort
  arm group type: Experimental
  description: Patients who participated in the trial with EGFR L858R mutation will be included in this arm
  intervention type: Drug
  intervention name: Toripalimab plus Chemotherapy
  description: Therapy was administered on a 21-day regimen for 3 cycles, with Toripalimab (240mg, d1), carboplatin (AUC=5, d1) + pemetrexed (500 mg/m2, d1) for patients with lung adenocarcinoma and carboplatin (AUC=5, d1) + albumin-bound paclitaxel (260 mg/m2, d1) for patients with other subtypes.
  arm group label: 19DEL cohort
  arm group label: L858R cohort
  criteria: 
  gender: All
  minimum age: 17 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Fan Yanf, M.D.
  role: Study Chair
  affiliation: Peking University People's Hospital
  last name: Fan Yang, M.D.
  phone: +86-010-88326657
  email: yangfan@pkuph.edu.cn
  last name: Xiang Yan, M.D.
  phone: +86-13581786750
  email: yxiang301@sina.com
  responsible party type: Principal Investigator
  investigator affiliation: Peking University People's Hospital
  investigator full name: Yang Fan, MD
  investigator title: Professor of Thoracic Surgery
  mesh term: Lung Neoplasms
  mesh term: Carcinoma, Non-Small-Cell Lung
  sharing ipd: Undecided