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/NCT06001671</url>
    </required_header>
    <id_info>
      <org_study_id>BEBT-109</org_study_id>
      <nct_id>NCT06001671</nct_id>
    </id_info>
    <brief_title>Antitumor Activity and Safety of BEBT-109, a Novel EGFR Inhibitor, in Previously Treated NSCLC</brief_title>
    <official_title>Antitumor Activity and Safety of BEBT-109, a Novel EGFR Inhibitor, in Previously Treated NSCLC With EGFR Exon 20 Insertion Mutations: a Phase 1B, Dose Escalation and Expansion Trial</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Hunan Province Tumor Hospital</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Hunan Province Tumor Hospital</source>
    <oversight_info>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This clinical study was a first-in-human, phase 1B, single-center, single-arm, open-label,&#xD;
        dose escalation and expansion trial that aimed to determine the safety, tolerability and&#xD;
        efficacy of BEBT-109 in patients with locally advanced or metastatic NSCLC harboring EGFR&#xD;
        exon20ins mutations who had received at least one line of previous treatment.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Completed</overall_status>
    <start_date type="Actual">October 27, 2020</start_date>
    <completion_date type="Actual">August 8, 2023</completion_date>
    <primary_completion_date type="Actual">March 1, 2023</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Single (Outcomes Assessor)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>DLT</measure>
      <time_frame>2 years</time_frame>
      <description>Defined as one of adverse events defined by NCI CTCAE V5.0 from the first day to the 28th day of the treatment period.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>MTD</measure>
      <time_frame>2 years</time_frame>
      <description>If only 1 of 3 participants in a dose group has DLT, 3 additional subjects in this group will be tested at the same dose level; If no participants developed DLT, the next dose study was conducted; If 2 of the first 3 participants developed DLT or 2 of 6 participants developed DLT, the previous dose of the dose was the maximum tolerated dose (MTD).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>ORR</measure>
      <time_frame>2 years</time_frame>
      <description>Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR</measure>
      <time_frame>2 years</time_frame>
      <description>Defined as the proportion of subjects with complete remission (CR), partial remission (PR) and stable disease (SD) to the total subjects</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Actual">23</enrollment>
    <condition>NSCLC</condition>
    <arm_group>
      <arm_group_label>BEBT-109 120mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BEBT-109 orally at an initial dose of 120 mg once daily.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>BEBT-109 180mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BEBT-109 orally at an initial dose of 180 mg once daily.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>BEBT-109 240mg</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>BEBT-109 orally at an initial dose of 240mg (120mg bid) once daily.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>BEBT-109</intervention_name>
      <description>BEBT-109 is based on the &quot;3+3&quot; model, with a dose ascent starting from 120mg qd</description>
      <arm_group_label>BEBT-109 120mg</arm_group_label>
      <arm_group_label>BEBT-109 180mg</arm_group_label>
      <arm_group_label>BEBT-109 240mg</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Sign written informed consent before implementing any trial-related procedures;&#xD;
  &#xD;
            -  Age ≥18 years and no limit on the gender.&#xD;
  &#xD;
            -  Histologically or cytologically confirmed locally advanced or metastatic NSCLC with&#xD;
               EGFR exon20ins mutation according to assessments made in local laboratories.&#xD;
  &#xD;
            -  Previous treatment and type of mutation:&#xD;
  &#xD;
                 1. Disease progression in doses extension cases may have been treated with an&#xD;
                    EGFR-TKI (e.g., gefitinib, erlotinib, eclitinib, afatinib, or dapatinib) and&#xD;
                    prior written test reports confirming EGFR T790M mutation.&#xD;
  &#xD;
                 2. Disease progression after prior chemotherapy regimen and/or EGFR-TKI treatment in&#xD;
                    dose-extension cases, and prior written test reports confirming EGFR 20 exon&#xD;
                    insertion mutations.&#xD;
  &#xD;
                 3. Disease progression following prior chemotherapy regimen and/or EGFR-TKI&#xD;
                    treatment in dose-extension cases, and prior written test reports confirming&#xD;
                    other rare mutations in EGFR (EGFR G719A, L861Q, or S768I point mutations).&#xD;
  &#xD;
                 4. Patients who are intolerant to chemotherapy or EGFR-TKI and have no other&#xD;
                    effective treatment can also be admitted to the dose expansion group after&#xD;
                    judgment by the investigator.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.&#xD;
  &#xD;
            -  Patients with brain metastasis were only enrolled if the metastases were stable.&#xD;
  &#xD;
            -  Subjects had at least 1 measurable lesion that met the RECIST 1.1 criteria.&#xD;
  &#xD;
            -  If female subjects are of childbearing potential, adequate contraception (e.g.,&#xD;
               condoms, etc.) should be used, no breastfeeding should be used, and a negative&#xD;
               pregnancy test before administration should be given.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Combined with any other malignancy (except adequately treated basal cell or squamous&#xD;
               cell skin cancer or carcinoma in situ of the cervix).&#xD;
  &#xD;
            -  Genetic testing confirmed the presence of C-MET amplification, HER-2 amplification and&#xD;
               KRAS mutations, and other genetic mutations that clearly confirm resistance to&#xD;
               EGFR-TKI.&#xD;
  &#xD;
            -  From the last treatment of EGFR-TKI (such as erlotinib, gefitinib, eclitinib, afatinib&#xD;
               or osimertinib, etc.) to the first administration of this clinical trial, the interval&#xD;
               is less than 14 days or 5 half-lives (whichever is longer is the exclusion criterion),&#xD;
               and the specific drugs involved are decided by the investigator based on comprehensive&#xD;
               consideration.&#xD;
  &#xD;
            -  In the 4 weeks prior to the first administration of the study treatment, participants&#xD;
               had used other anticancer drugs (including immune cell therapy) in the previous&#xD;
               treatment regimen.&#xD;
  &#xD;
            -  Those who have not withdrawn from other clinical trials within 4 weeks prior to the&#xD;
               first administration of the study treatment.&#xD;
  &#xD;
            -  Previous homogeneous drug restriction:&#xD;
  &#xD;
                 1. Patients with EGFR mutation previously treated with osimertinib or other&#xD;
                    third-generation EGFR inhibitor drugs (eg, ivelitinib, emetinib, and eflotinib) ;&#xD;
  &#xD;
                 2. EGFR exon20 insertion mutants have used drugs that target EGFR 20 exon insertion&#xD;
                    mutants (e.g. Poziotinib tarloxotinib TAK788 JNJ-61186372 CLN-081, etc.)&#xD;
  &#xD;
                 3. Other EGFR rare mutations (EGFR G719A, L861Q, or S768I point mutations) have been&#xD;
                    treated with afatinib.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <location>
      <facility>
        <name>Hunan Cancer hospital</name>
        <address>
          <city>Changsha</city>
          <state>Hunan</state>
          <country>China</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 7, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 20, 2023</last_update_submitted>
    <last_update_submitted_qc>August 20, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 23, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Hunan Province Tumor Hospital</investigator_affiliation>
      <investigator_full_name>Yongchang Zhang</investigator_full_name>
      <investigator_title>Professor, Deputy Director of Thoracic Oncology Department</investigator_title>
    </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>
    <!-- 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/NCT06001671
  org study id: BEBT-109
  nct id: NCT06001671
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This clinical study was a first-in-human, phase 1B, single-center, single-arm, open-label,
        dose escalation and expansion trial that aimed to determine the safety, tolerability and
        efficacy of BEBT-109 in patients with locally advanced or metastatic NSCLC harboring EGFR
        exon20ins mutations who had received at least one line of previous treatment.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  primary purpose: Treatment
  masking: Single (Outcomes Assessor)
  measure: DLT
  time frame: 2 years
  description: Defined as one of adverse events defined by NCI CTCAE V5.0 from the first day to the 28th day of the treatment period.
  measure: MTD
  time frame: 2 years
  description: If only 1 of 3 participants in a dose group has DLT, 3 additional subjects in this group will be tested at the same dose level; If no participants developed DLT, the next dose study was conducted; If 2 of the first 3 participants developed DLT or 2 of 6 participants developed DLT, the previous dose of the dose was the maximum tolerated dose (MTD).
  measure: ORR
  time frame: 2 years
  description: Defined as the proportion of subjects in complete remission (CR) and partial remission (PR) to the total subjects
  measure: DCR
  time frame: 2 years
  description: Defined as the proportion of subjects with complete remission (CR), partial remission (PR) and stable disease (SD) to the total subjects
  arm group label: BEBT-109 120mg
  arm group type: Experimental
  description: BEBT-109 orally at an initial dose of 120 mg once daily.
  arm group label: BEBT-109 180mg
  arm group type: Experimental
  description: BEBT-109 orally at an initial dose of 180 mg once daily.
  arm group label: BEBT-109 240mg
  arm group type: Experimental
  description: BEBT-109 orally at an initial dose of 240mg (120mg bid) once daily.
  intervention type: Drug
  intervention name: BEBT-109
  description: BEBT-109 is based on the "3+3" model, with a dose ascent starting from 120mg qd
  arm group label: BEBT-109 120mg
  arm group label: BEBT-109 180mg
  arm group label: BEBT-109 240mg
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  facility: 
  country: China
  responsible party type: Principal Investigator
  investigator affiliation: Hunan Province Tumor Hospital
  investigator full name: Yongchang Zhang
  investigator title: Professor, Deputy Director of Thoracic Oncology Department
  mesh term: Carcinoma, Non-Small-Cell Lung