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/NCT05994131</url>
    </required_header>
    <id_info>
      <org_study_id>IN10018-014</org_study_id>
      <nct_id>NCT05994131</nct_id>
    </id_info>
    <brief_title>IN10018 Combination Therapy in Advanced EGFR Mutation-positive NSCLC</brief_title>
    <official_title>A Multicenter, Open-label, Phase Ib/II Clinical Trial to Evaluate the Safety, Tolerance, Pharmacokinetics and Anti-tumor Efficacy of IN10018 Combined With Third-generation EGFR-TKI in Patients With Advanced EGFR Mutation-positive NSCLC</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>InxMed (Shanghai) Co., Ltd.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>InxMed (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>
        This is a multicenter, open-label, phase Ib/II clinical study to evaluate the safety,&#xD;
        tolerability, pharmacokinetics and antitumor efficacy of IN10018 in combination with&#xD;
        third-generation EGFR-TKI (Furmonertinib is the proposed) in previously-treated or naïve&#xD;
        advanced EGFR-mutation positive NSCLC.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study includes 2 parts: Phase Ib-Dose Confirmation and Phase II-Dose Expansion. And 3&#xD;
        cohorts are set up in this study as cohort 1 to enroll subjects currently accepting&#xD;
        third-generation EGFR-TKI (Furmonertinib is proposed) as first-line treatment, cohort 2 to&#xD;
        enroll subjects who previously accepted third-generation EGFR-TKI treatment and 1-2 lines&#xD;
        chemotherapy, and cohort 3 to enroll treatment-naive advanced EGFR mutation-positive NSCLC&#xD;
        subjects.&#xD;
  &#xD;
        The phase Ib-dose confirmation part will be conducted in cohort 2 and aim to determine the&#xD;
        recommended phase II dose (RP2D) of IN10018 in combination with Furmonertinib. Phase II-Dose&#xD;
        Expansion part will be conducted in cohort 1-3 and further explore the antitumor efficacy,&#xD;
        safety and PK of IN10018 in combination with Furmonertinib in subjects with&#xD;
        previously-treated or naïve advanced EGFR mutation-positive NSCLC.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">July 13, 2023</start_date>
    <completion_date type="Anticipated">July 31, 2026</completion_date>
    <primary_completion_date type="Anticipated">July 31, 2026</primary_completion_date>
    <phase>Phase 1/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>Recommended phase II dose (RP2D) of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced NSCLC.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>ORR of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Defined as the proportion of subjects with complete response (CR) or partial response (PR)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Tumor Shrinkage Rate (TSR) of IN10018 in combination with third-generation EGFR-TKI in cohort 3 of advanced treatment-naive EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Defined as the percentage of subjects with the best shrinkage rate of target lesions ≥ 70% and simultaneously with a best response of partial response (PR) or complete response (CR).</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>PFS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Defined as the time from the first dose of study treatment/randomization to first documentation of disease progression or to death due to any cause, whichever comes first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DOR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>DCR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Defined as the proportion of patients with CR, PR, or stable disease (SD).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>OS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.</measure>
      <time_frame>3 years</time_frame>
      <description>Defined as the time from the first dose of study treatment/randomization to the date of death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Number of patients with adverse event</measure>
      <time_frame>3 years</time_frame>
      <description>The number of participants who experienced AEs is presented.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK: AUC of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>Area under the concentration-time curve (AUC)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK: Cmax of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>Maximum concentration (Cmax)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK:Ctrough of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>Trough concentration (Ctrough)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK:Tmax of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>Time to Cmax (Tmax)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK:t1/2 of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>Elimination half-life (t1/2).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK:CL/F of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>apparent clearance (CL/F)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>PK:Vd/F of IN10018 following single dose administration and at steady state</measure>
      <time_frame>3 years</time_frame>
      <description>Apparent volume of distribution (Vd/F)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">110</enrollment>
    <condition>NSCLC</condition>
    <arm_group>
      <arm_group_label>Experimental Group in cohort 1, cohort 2, and cohort 3</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>IN10018+Furmonertinib</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control Group in cohort 3</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Furmonertinib</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>IN10018</intervention_name>
      <description>orally taken once daily</description>
      <arm_group_label>Experimental Group in cohort 1, cohort 2, and cohort 3</arm_group_label>
      <other_name>BI 853520</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Furmonertinib</intervention_name>
      <description>orally taken once daily</description>
      <arm_group_label>Control Group in cohort 3</arm_group_label>
      <arm_group_label>Experimental Group in cohort 1, cohort 2, and cohort 3</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria&#xD;
  &#xD;
            1. Be able to understand and be willing to sign informed consent.&#xD;
  &#xD;
            2. Male or female aged ≥ 18 years old at the time of signing informed consent.&#xD;
  &#xD;
            3. Histologically or cytologically confirmed locally advanced or metastatic NSCLC, who is&#xD;
               not suitable for radical surgery or radiotherapy.&#xD;
  &#xD;
            4. Documented EGFR mutations known to be associated with EGFR-TKI sensitivity, including&#xD;
               Ex19del or L858R. Except for EGFR-TKI sensitive mutation, coexisting with other EGFR&#xD;
               mutation types such as T790M can be allowed.&#xD;
  &#xD;
            5. Prior systemic antitumor therapy allowed are listed as follows:&#xD;
  &#xD;
                 -  Cohort 1: Subjects who are on the treatment of Furmonertinib as the first-line&#xD;
                    treatment setting.&#xD;
  &#xD;
                 -  Cohort 2: Subjects failed in third-generation EGFR-TKI treatment and also failed&#xD;
                    in or were intolerant to 1-2 lines of chemotherapy.&#xD;
  &#xD;
                 -  Cohort 3: subjects who haven't accepted any systemic therapy before. Prior&#xD;
                    adjuvant or neoadjuvant chemotherapy is permitted if an interval from the lost&#xD;
                    dose of adjuvant or neoadjuvant chemotherapy to the first documented PD is &gt;6&#xD;
                    months.&#xD;
  &#xD;
            6. Measurable lesions at baseline according to RECIST 1.1 criteria.&#xD;
  &#xD;
            7. Has an ECOG performance status of 0 or 1.&#xD;
  &#xD;
            8. Estimated life expectancy is more than 3 months.&#xD;
  &#xD;
            9. Adequate bone marrow, liver, renal, and coagulation function within 7 days prior to&#xD;
               the first dose of study treatment/randomization.&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
            1. Have experienced major surgical procedures or major trauma within 28 days prior to the&#xD;
               first dose of study treatment/randomization.&#xD;
  &#xD;
            2. Have received the following prior systemic antitumor therapy:&#xD;
  &#xD;
                 -  Cohort 1: Have received chemotherapy, target therapy besides Furmonertinib,&#xD;
                    immunotherapy, biological therapy, and other antitumor drugs.&#xD;
  &#xD;
                 -  Cohort 2: Have received chemotherapy, targeted therapy, immunotherapy, biological&#xD;
                    therapy, and other antitumor drugs within 28 days prior to the first dose of&#xD;
                    study treatment.&#xD;
  &#xD;
                 -  Cohort 3: Have received systemic antitumor therapy for locally-advanced or&#xD;
                    metastatic NSCLC including chemotherapy, target therapy, immunotherapy,&#xD;
                    biotherapy, etc.&#xD;
  &#xD;
            3. Cohort 2 only： Presence of other gene mutations, including ALK mutation, MET&#xD;
               amplification, HER2 amplification, RAS mutation, etc. after progression on prior&#xD;
               third-generation EGFR-TKI treatment.&#xD;
  &#xD;
            4. Cohort 3 only：Has received the treatment of EGFR-TKI。&#xD;
  &#xD;
            5. Prior FAK inhibitors treatment.&#xD;
  &#xD;
            6. Have received systemic administration of potent inhibitors/inducers of CYP3A4, or P-gp&#xD;
               inhibitors within 14 days prior to the first dose of treatment/randomization or are&#xD;
               expected to receive systemic administration of these drugs during study treatment.&#xD;
  &#xD;
            7. Has received radiotherapy for study disease or radiotherapeutic area covered for more&#xD;
               than 30% of the bone marrow within 28 days prior to the first dose of study&#xD;
               treatment/randomization.&#xD;
  &#xD;
            8. Has had interstitial lung disease (ILD), drug-induced ILD, radiation pneumonia&#xD;
               requiring steroid therapy; or diagnosis of clinically active ILD during the screening&#xD;
               period.&#xD;
  &#xD;
            9. Has a prior history of other malignancy within 3 years prior to signing informed&#xD;
               consent.&#xD;
  &#xD;
           10. Has known symptoms of spinal cord compression, active central nervous system (CNS)&#xD;
               metastases, and/or carcinomatous meningitis.&#xD;
  &#xD;
           11. Has a history of severe cardiovascular or cerebrovascular diseases within 6 months&#xD;
               prior to the first dose of study treatment/randomization.&#xD;
  &#xD;
           12. Has known uncontrollable pleural effusion, pericardial effusion, and ascites.&#xD;
  &#xD;
           13. Has hemoptysis within 1 month prior to the first dose of study treatment/randomization&#xD;
               with a blood volume of ≥2.5 mL every time or expected to require continuous hemostasis&#xD;
               therapy during the study treatment.&#xD;
  &#xD;
           14. Has active infections that are poorly controlled by systemic treatment.&#xD;
  &#xD;
           15. Has active tuberculosis.&#xD;
  &#xD;
           16. Known allergy, hypersensitivity or intolerance to IN10018 and/or third-generation&#xD;
               EGFR-TKI, or their ingredients.&#xD;
  &#xD;
           17. Pregnant or lactating women.&#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>Caicun Zhou</last_name>
      <role>Principal Investigator</role>
      <affiliation>Shanghai Pulmonary Hospital, Shanghai, China</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Bohong Zhang</last_name>
      <phone>+86 18801955197</phone>
      <email>bohong.zhang@inxmed.com</email>
    </overall_contact>
    <location>
      <facility>
        <name>Shanghai Pulmonary Hospital</name>
        <address>
          <city>Shanghai</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Caicun Zhou</last_name>
        <phone>+86 13301825532</phone>
        <email>caicunzhoudr@163.com</email>
      </contact>
      <investigator>
        <last_name>Caicun Zhou</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 16, 2023</study_first_posted>
    <last_update_submitted>August 8, 2023</last_update_submitted>
    <last_update_submitted_qc>August 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 16, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>EGFR mutation-positve</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>Aflutinib</mesh_term>
    </intervention_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/NCT05994131
  org study id: IN10018-014
  nct id: NCT05994131
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, open-label, phase Ib/II clinical study to evaluate the safety,
        tolerability, pharmacokinetics and antitumor efficacy of IN10018 in combination with
        third-generation EGFR-TKI (Furmonertinib is the proposed) in previously-treated or naïve
        advanced EGFR-mutation positive NSCLC.
  This study includes 2 parts: Phase Ib-Dose Confirmation and Phase II-Dose Expansion. And 3
        cohorts are set up in this study as cohort 1 to enroll subjects currently accepting
        third-generation EGFR-TKI (Furmonertinib is proposed) as first-line treatment, cohort 2 to
        enroll subjects who previously accepted third-generation EGFR-TKI treatment and 1-2 lines
        chemotherapy, and cohort 3 to enroll treatment-naive advanced EGFR mutation-positive NSCLC
        subjects.
  
        The phase Ib-dose confirmation part will be conducted in cohort 2 and aim to determine the
        recommended phase II dose (RP2D) of IN10018 in combination with Furmonertinib. Phase II-Dose
        Expansion part will be conducted in cohort 1-3 and further explore the antitumor efficacy,
        safety and PK of IN10018 in combination with Furmonertinib in subjects with
        previously-treated or naïve advanced EGFR mutation-positive NSCLC.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Recommended phase II dose (RP2D) of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced NSCLC.
  measure: ORR of IN10018 in combination with third-generation EGFR-TKI in subjects with advanced EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Defined as the proportion of subjects with complete response (CR) or partial response (PR)
  measure: Tumor Shrinkage Rate (TSR) of IN10018 in combination with third-generation EGFR-TKI in cohort 3 of advanced treatment-naive EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Defined as the percentage of subjects with the best shrinkage rate of target lesions ≥ 70% and simultaneously with a best response of partial response (PR) or complete response (CR).
  measure: PFS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Defined as the time from the first dose of study treatment/randomization to first documentation of disease progression or to death due to any cause, whichever comes first.
  measure: DOR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Defined as the time from start of the first documentation of CR or PR to the first documentation of disease progression or to death due to any cause, whichever comes first.
  measure: DCR of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Defined as the proportion of patients with CR, PR, or stable disease (SD).
  measure: OS of IN10018 in combination with third-generation EGFR-TKI in advanced EGFR mutation-positive NSCLC.
  time frame: 3 years
  description: Defined as the time from the first dose of study treatment/randomization to the date of death due to any cause.
  measure: Number of patients with adverse event
  time frame: 3 years
  description: The number of participants who experienced AEs is presented.
  measure: PK: AUC of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: Area under the concentration-time curve (AUC)
  measure: PK: Cmax of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: Maximum concentration (Cmax)
  measure: PK:Ctrough of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: Trough concentration (Ctrough)
  measure: PK:Tmax of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: Time to Cmax (Tmax)
  measure: PK:t1/2 of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: Elimination half-life (t1/2).
  measure: PK:CL/F of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: apparent clearance (CL/F)
  measure: PK:Vd/F of IN10018 following single dose administration and at steady state
  time frame: 3 years
  description: Apparent volume of distribution (Vd/F)
  arm group label: Experimental Group in cohort 1, cohort 2, and cohort 3
  arm group type: Experimental
  description: IN10018+Furmonertinib
  arm group label: Control Group in cohort 3
  arm group type: Active Comparator
  description: Furmonertinib
  intervention type: Drug
  intervention name: IN10018
  description: orally taken once daily
  arm group label: Experimental Group in cohort 1, cohort 2, and cohort 3
  other name: BI 853520
  intervention type: Drug
  intervention name: Furmonertinib
  description: orally taken once daily
  arm group label: Control Group in cohort 3
  arm group label: Experimental Group in cohort 1, cohort 2, and cohort 3
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Caicun Zhou
  role: Principal Investigator
  affiliation: Shanghai Pulmonary Hospital, Shanghai, China
  last name: Bohong Zhang
  phone: +86 18801955197
  email: bohong.zhang@inxmed.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  country: China
  responsible party type: Sponsor
  mesh term: Carcinoma, Non-Small-Cell Lung
  mesh term: Aflutinib