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/NCT06029816</url>
    </required_header>
    <id_info>
      <org_study_id>CVL009-2001</org_study_id>
      <secondary_id>Chinadrugtrials</secondary_id>
      <nct_id>NCT06029816</nct_id>
    </id_info>
    <brief_title>Neratinib Tablets in the Treatment of Advanced NSCLC With Rare EGFR Mutations</brief_title>
    <acronym>CVL009-2001</acronym>
    <official_title>A Single-arm, Open-label, Multicenter Phase II Clinical Study of Neratinib Tablets in the Treatment of Advanced NSCLC With Rare EGFR Mutations</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Convalife (Shanghai) Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Convalife (Shanghai) Co., Ltd.</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Single-arm, open-label, multicenter phase II clinical study&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Fourteen patients each had three mutation sites and 42 patients were co-enrolled，To evaluate&#xD;
        the objective response rate (ORR) of neratinib Tablets in advanced NSCLC with rare EGFR&#xD;
        mutations (including G719X, E709X in exon 18, S768I in exon 20 and L861Q in exon 21).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 20, 2023</start_date>
    <completion_date type="Anticipated">December 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">December 30, 2024</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>Fourteen patients each had three mutation sites and 42 patients were co-enrolled</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>IRC-assessed objective response rate (ORR)</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>IRC-assessed objective response rate (ORR)</description>
    </primary_outcome>
    <other_outcome>
      <measure>ORR by investigator</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>ORR by investigator</description>
    </other_outcome>
    <other_outcome>
      <measure>Overall Survival (OS)</measure>
      <time_frame>Through study completion, an average of 1 year</time_frame>
      <description>Overall Survival (OS)</description>
    </other_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">42</enrollment>
    <condition>NSCLC</condition>
    <arm_group>
      <arm_group_label>Arm1-Exon 18</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Exon 18 G719X, E709X, etc，Up to 14 patients will be enrolled in this group and will be treated with neratinib tablets in 28-day cycles，</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm2-Exon 20</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>S768I in exon 20，Up to 14 patients will be enrolled in this group and will be treated with neratinib tablets in 28-day cycles，</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Arm3-Exon 21</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>L861Q of exon 21，Up to 14 patients will be enrolled in this group and will be treated with neratinib tablets in 28-day cycles，</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Neratinib tablets</intervention_name>
      <description>Neratinib tablets</description>
      <arm_group_label>Arm1-Exon 18</arm_group_label>
      <arm_group_label>Arm2-Exon 20</arm_group_label>
      <arm_group_label>Arm3-Exon 21</arm_group_label>
      <other_name>Epilepsy</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age ≥ 18 years;&#xD;
  &#xD;
            2. Histologically or cytologically confirmed non-small cell lung cancer, stage IIIB or IV&#xD;
               according to IASLC 2009;&#xD;
  &#xD;
            3. Tissue or blood samples are confirmed by the central laboratory or research center as&#xD;
               rare EGFR mutations, including exon 18 G719X, E709X, etc., S768I in exon 20 and at&#xD;
               least one of the L861Q mutations in exon 21;&#xD;
  &#xD;
            4. Ineffective or intolerant to standard treatment regimens, and disease progression&#xD;
               after treatment;&#xD;
  &#xD;
            5. The number of previous chemotherapy regimens does not exceed 2 (a. replacement of&#xD;
               platinum drugs for drug toxicity reasons is counted as a regimen; b. postoperative&#xD;
               adjuvant chemotherapy, from the end of treatment to recurrence &gt; 6 months is not&#xD;
               counted as a previous chemotherapy regimen);&#xD;
  &#xD;
            6. ECOG standard score 0-1;&#xD;
  &#xD;
            7. Predicted survival ≥ 12 weeks;&#xD;
  &#xD;
            8. Presence of measurable lesions according to RECIST 1.1: At least one lesion that is&#xD;
               not irradiated, ≥ 10 mm in long diameter (lymph node lesions need to be ≥ 15 mm in&#xD;
               short diameter), and can be accurately measured at baseline and can be repeatedly&#xD;
               measured under CT or MRI; If the subject only has post-radiotherapy lesion, and this&#xD;
               lesion has been confirmed as imaging progression and can be measured, it can be&#xD;
               selected as target lesion (except for brain lesion), and brain lesion is not included&#xD;
               as measurable target lesion;&#xD;
  &#xD;
            9. Subjects with asymptomatic brain metastases or brain metastases can be included in&#xD;
               this study when the following conditions are met: brain metastases are treated and&#xD;
               stable, such as clinical examination and brain scan (MRI or CT scan) confirmed at&#xD;
               least 4 no evidence of lesion progression during the screening period, no neurological&#xD;
               symptoms and no need for corticosteroid therapy. If the subject has brain metastases&#xD;
               that have been treated surgically or with radiation, a time window of ≥ 4 weeks is&#xD;
               required before the first dose of nelatidine tablets to ensure that adverse events&#xD;
               associated with radiation or surgical treatment have decreased to ≤ Grade 1;&#xD;
  &#xD;
           10. Bone marrow reserve or organ function needs to meet the following laboratory value&#xD;
               criteria:&#xD;
  &#xD;
                 -  Absolute neutrophil count (ANC) ≥ 1.5 × 109/L&#xD;
  &#xD;
                 -  Platelet count (PLT) ≥ 90 × 109/L&#xD;
  &#xD;
                 -  Hemoglobin (Hb) ≥ 90 g/L&#xD;
  &#xD;
                 -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN;&#xD;
                    ≤ 5 × ULN in the presence of liver metastases&#xD;
  &#xD;
                 -  Serum total bilirubin (TBIL) ≤ 1.5 × ULN&#xD;
  &#xD;
                 -  Blood urea nitrogen/urea nitrogen (UREA/BUN) and creatinine (Cr) ≤ 1.5 × ULN&#xD;
  &#xD;
                 -  Coagulation international normalized ratio (INR) ≤ 1.5 ULN and APTT ≤ 1.5 ULN;&#xD;
  &#xD;
                 -  Urine protein &lt; 2 + (when baseline urine protein is 2 +, 24-hour urine protein&#xD;
                    quantification should be performed, and inclusion can only be made when ≤ 1 g) *&#xD;
                    ULN = upper limit of normal&#xD;
  &#xD;
           11. Women of childbearing potential should agree to take contraceptive measures (such as&#xD;
               intrauterine device, contraceptive or condom) during the study and within 6 months&#xD;
               after the end of the study; 7. Blood pregnancy test is negative before enrollment and&#xD;
               patients must be non-lactating; men should agree to take contraceptive measures during&#xD;
               the study and within 6 months after the end of the study;&#xD;
  &#xD;
           12. Patients voluntarily participate in this study, sign the informed consent form, and&#xD;
               have good compliance.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Received any of the following treatments: 1. previous treatment with any EGFR tyrosine&#xD;
               kinase inhibitor; 2. major surgery 4 times before the first dose of the study drug; c.&#xD;
               4 times before the first dose of the study drug, more than 30% of bone marrow&#xD;
               irradiation, or extensive radiotherapy; d. within 7 days before the first dose of the&#xD;
               study drug, the use of CYP3A4 strong inhibitors, inducers or drugs that are CYP3A4&#xD;
               sensitive substrates with a narrow therapeutic window;&#xD;
  &#xD;
            2. Patients with other malignant tumors and need standard treatment or major surgery&#xD;
               within 2 years after the first dose of study treatment;&#xD;
  &#xD;
            3. In the beginning of the study treatment, there are greater than CTCAE grade 1 failed&#xD;
               to alleviate the residual toxicity of previous treatment, except alopecia and previous&#xD;
               chemotherapy-induced grade 2 neurotoxicity;&#xD;
  &#xD;
            4. Spinal cord compression or brain metastasis, unless asymptomatic, stable condition,&#xD;
               and not requiring steroid therapy for at least 2 weeks before the first dose of study&#xD;
               treatment;&#xD;
  &#xD;
            5. Poor blood pressure control after drug treatment (systolic blood pressure &gt; 180 mmHg&#xD;
               and/or diastolic blood pressure &gt; 100 mmHg);&#xD;
  &#xD;
            6. Patients with severe or uncontrollable systemic diseases, including gastrointestinal&#xD;
               ulcers and bleeding and other diseases;&#xD;
  &#xD;
            7. There are many factors that affect the oral administration of drugs (such as inability&#xD;
               to swallow, chronic diarrhea, intestinal obstruction and other gastrointestinal&#xD;
               diseases or abnormalities);&#xD;
  &#xD;
            8. 12 ECG: QTcF: female &gt; 470 ms, male &gt; 450 ms;&#xD;
  &#xD;
            9. Echocardiography: score (LVEF) ≤ 50%;&#xD;
  &#xD;
           10. History of interstitial lung disease, drug-induced interstitial lung disease,&#xD;
               radiation pneumonitis requiring steroid therapy or any evidence of clinically active&#xD;
               interstitial lung disease;&#xD;
  &#xD;
           11. History of immunodeficiency, including HIV test positive, active hepatitis B/C&#xD;
               (HBV-DNA &gt; 1000 IU/mL or &gt; 2500 copies/mL, HCV-RNA ≥ 10 ³ copies/mL) or suffering from&#xD;
               other acquired, congenital immunodeficiency diseases, or history of organ&#xD;
               transplantation;&#xD;
  &#xD;
           12. Women who are lactating or have a positive pregnancy test result before the first dose&#xD;
               of study treatment;&#xD;
  &#xD;
           13. 4 Participated in any other drug clinical study before the first dose;&#xD;
  &#xD;
           14. The investigator judges that there are any patients who endanger the patient's safety,&#xD;
               interfere with the study assessment, and have poor compliance;&#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>Wenfeng Fang</last_name>
      <role>Principal Investigator</role>
      <affiliation>Sun Yat-sen University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Qiong Wang</last_name>
      <phone>（021）6877 3638</phone>
      <email>qiong.wang@convalife.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Dong Wang</last_name>
      <phone>（021）6877 3638</phone>
      <email>dong.wang@convalife.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Sun Yat-sen University Cancer Center</name>
        <address>
          <city>Guangzhou</city>
          <state>Guangdong</state>
          <zip>510060</zip>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Ran Xu</last_name>
        <phone>020-87343565</phone>
        <email>xuran@sysucc.org.cn</email>
      </contact>
      <investigator>
        <last_name>Wenfeng Fang</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Ning Li</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Ying Cheng</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Baogang Liu</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Haiyong Wang</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>lin Wu</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Qiming Wang</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Runxiang Yang</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 31, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>NSCLC</keyword>
    <keyword>EGFR</keyword>
    <keyword>Neratinib tablets</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>
    <patient_data>
      <sharing_ipd>No</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/NCT06029816
  org study id: CVL009-2001
  secondary id: Chinadrugtrials
  nct id: NCT06029816
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Single-arm, open-label, multicenter phase II clinical study
  Fourteen patients each had three mutation sites and 42 patients were co-enrolled，To evaluate
        the objective response rate (ORR) of neratinib Tablets in advanced NSCLC with rare EGFR
        mutations (including G719X, E709X in exon 18, S768I in exon 20 and L861Q in exon 21).
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  intervention model description: Fourteen patients each had three mutation sites and 42 patients were co-enrolled
  primary purpose: Treatment
  masking: None (Open Label)
  measure: IRC-assessed objective response rate (ORR)
  time frame: Through study completion, an average of 1 year
  description: IRC-assessed objective response rate (ORR)
  measure: ORR by investigator
  time frame: Through study completion, an average of 1 year
  description: ORR by investigator
  measure: Overall Survival (OS)
  time frame: Through study completion, an average of 1 year
  description: Overall Survival (OS)
  arm group label: Arm1-Exon 18
  arm group type: Experimental
  description: Exon 18 G719X, E709X, etc，Up to 14 patients will be enrolled in this group and will be treated with neratinib tablets in 28-day cycles，
  arm group label: Arm2-Exon 20
  arm group type: Experimental
  description: S768I in exon 20，Up to 14 patients will be enrolled in this group and will be treated with neratinib tablets in 28-day cycles，
  arm group label: Arm3-Exon 21
  arm group type: Experimental
  description: L861Q of exon 21，Up to 14 patients will be enrolled in this group and will be treated with neratinib tablets in 28-day cycles，
  intervention type: Drug
  intervention name: Neratinib tablets
  description: Neratinib tablets
  arm group label: Arm1-Exon 18
  arm group label: Arm2-Exon 20
  arm group label: Arm3-Exon 21
  other name: Epilepsy
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Wenfeng Fang
  role: Principal Investigator
  affiliation: Sun Yat-sen University
  last name: Qiong Wang
  phone: （021）6877 3638
  email: qiong.wang@convalife.com
  last name: Dong Wang
  phone: （021）6877 3638
  email: dong.wang@convalife.com
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung
  sharing ipd: No