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/NCT06030258</url>
    </required_header>
    <id_info>
      <org_study_id>IN10018-019</org_study_id>
      <nct_id>NCT06030258</nct_id>
    </id_info>
    <brief_title>IN10018 Combination Therapy in Treatment-naïve ES-SCLC</brief_title>
    <official_title>A Phase Ib/II Clinical Trial to Evaluate the Anti-tumor Efficacy, Safety, Tolerability, and Pharmacokinetics of IN10018 Combined With Anti-PD-1/L1 Antibody and Chemotherapy as First-line Treatment in Extensive-stage Small Cell Lung Cancer</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>
      <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, Randomized, phase Ib/II clinical study to evaluate the&#xD;
        anti-tumor efficacy, safety, tolerability, and PK of IN10018 in combination with anti-PD-1/L1&#xD;
        monoclonal antibody (Tislelizumab is proposed as the combination drug) and chemotherapy&#xD;
        (platinum and etoposide) as the first-line treatment in Extensive-stage small cell lung&#xD;
        cancer (ES-SCLC).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study consists of 2 parts: 1) Phase Ib-Dose Confirmation part: To assess the PK&#xD;
        parameters, safety and recommended phase II dose (RP2D) of IN10018 in combination with&#xD;
        anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed as the combination drug), platinum&#xD;
        (carboplatin is proposed as the combination drug) and etoposide as the first-line treatment&#xD;
        in ES-SCLC. 2) Phase II-Dose Expansion part: To assess the antitumor efficacy, safety and&#xD;
        tolerability in the experimental group of IN10018 in combination with Tislelizumab,&#xD;
        carboplatin and etoposide as compared to the control group of Tislelizumab in combination&#xD;
        with carboplatin and etoposide as the first-line treatment in ES-SCLC.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">November 5, 2023</start_date>
    <completion_date type="Anticipated">October 21, 2025</completion_date>
    <primary_completion_date type="Anticipated">January 24, 2025</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>To identify the Recommended phase II dose (RP2D) of IN10018 in combination with Tislelizumab, Carboplatin and Etoposide in first-line ES-SCLC.</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Evaluate proportion of patients suffered with AEs defined as dose-limited toxicities (DLTs) per protocol; and RP2D will be determined per the incidence of AEs defined as DLTs.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Progress free survival (PFS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR based on RECIST 1.1</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>PFS of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per investigator based on RECIST 1.1</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Objective response rate (ORR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1.</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the proportion of subjects with complete response (CR) or partial response (PR).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Duration of objective response (DOR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1.</measure>
      <time_frame>Up to 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>Disease Control Rate (DCR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the proportion of patients with CR, PR, or stable disease (SD).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival (OS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC.</measure>
      <time_frame>Up to 3 years</time_frame>
      <description>Defined as the time from 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>Up to 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>Up to 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>Up to 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>Up to 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>Up to 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>Up to 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>Up to 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>Up to 3 years</time_frame>
      <description>Apparent volume of distribution (Vd/F)</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">120</enrollment>
    <condition>Small Cell Lung Cancer Extensive Stage</condition>
    <arm_group>
      <arm_group_label>Experimental group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>IN10018 in combination with Tislelizumab, carboplatin and etoposide as the first-line treatment in ES-SCLC.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Tislelizumab in combination with carboplatin and etoposide as the first-line treatment in ES-SCLC</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</arm_group_label>
      <other_name>BI 853520</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Tislelizumab</intervention_name>
      <description>200mg D1, Q3W, intravenously</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Experimental group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Carboplatin</intervention_name>
      <description>AUC 5 mg/ml/min, D1, Q3W, intravenously</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Experimental group</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Etoposide</intervention_name>
      <description>Etoposide 100 mg/m2, D1-D3, Q3W, intravenously</description>
      <arm_group_label>Control group</arm_group_label>
      <arm_group_label>Experimental group</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria&#xD;
  &#xD;
            1. Male or female aged 18-75 years old at the time of signing informed consent.&#xD;
  &#xD;
            2. Be able to understand and be willing to sign informed consent.&#xD;
  &#xD;
            3. Histologically confirmed ES-SCLC (according to the Veterans Administration Lung Study&#xD;
               Group (VALG) staging system), which is not suitable for locally radical therapy.&#xD;
  &#xD;
            4. Has not received any systemic antitumor therapy for ES-SCLC.&#xD;
  &#xD;
            5. Has at least one measurable tumor lesion per RECIST 1.1.&#xD;
  &#xD;
            6. Has an ECOG performance status of 0 or 1.&#xD;
  &#xD;
            7. Estimated life expectancy is more than 3 months.&#xD;
  &#xD;
            8. Has adequate organ function of bone marrow, liver, kidney, and coagulation. Relative&#xD;
               laboratory tests must be performed within 7 days prior to first dose of study&#xD;
               treatment/randomization.&#xD;
  &#xD;
            9. AEs due to prior antitumor therapy must be recovered to ≤ Grade 1 (CTCAE v5.0) or a&#xD;
               steady state as assessed by investigators&#xD;
  &#xD;
           10. Subjects (male and female) with childbearing potential must agree to use contraception&#xD;
               during the treatment phase and through 3 months after the last dose of study&#xD;
               treatment.&#xD;
  &#xD;
          Exclusion Criteria&#xD;
  &#xD;
            1. Has known active or untreated central nervous system (CNS) metastases, and/or&#xD;
               carcinomatous meningitis.&#xD;
  &#xD;
            2. Spinal cord compression without surgery and/or radiation therapy, or previously&#xD;
               diagnosed and treated spinal cord compression without evidence that disease has been&#xD;
               clinically stable for at least 7 days prior to the first dose of study&#xD;
               treatment/randomization.&#xD;
  &#xD;
            3. Pleural, pericardial or abdominal effusion that are clinically symptomatic and require&#xD;
               puncture or drainage.&#xD;
  &#xD;
            4. Symptomatic hypercalcemia.&#xD;
  &#xD;
            5. Malignancies other than the study disease within 3 years prior to the first dose of&#xD;
               study treatment/randomization.&#xD;
  &#xD;
            6. Have received palliative radiotherapy for bone metastasis within 14 days prior to the&#xD;
               first dose of study treatment/randomization.&#xD;
  &#xD;
            7. Have had allogeneic haematopoietic stem cell transplantation or organ transplantation.&#xD;
  &#xD;
            8. History of active autoimmune disease required systemic treatment (including but not&#xD;
               limited to drugs for disease control, corticosteroids, or immunosuppressive drugs)&#xD;
               within the past 2 years.&#xD;
  &#xD;
            9. Have an immunodeficiency disorder or have received systemic steroid therapy&#xD;
               (prednisone or equivalent corticosteroid &gt; 10 mg/day) or other immunosuppressants&#xD;
               within 7 days prior to the first dose of study treatment/randomization.&#xD;
  &#xD;
           10. History of idiopathic pulmonary fibrosis, idiopathic pneumonia and organizing&#xD;
               pneumonia, and interstitial pneumonitis or active pneumonia diagnosed per imaging&#xD;
               examination at baseline.&#xD;
  &#xD;
           11. Have had FAK inhibitors treatment.&#xD;
  &#xD;
           12. Has a history of major cardiovascular or cerebrovascular diseases within 6 months&#xD;
               prior to the first dose of study treatment/randomization.&#xD;
  &#xD;
           13. Have malabsorption syndrome or cannot take study drugs orally.&#xD;
  &#xD;
           14. Any active infection requiring systemic therapy within 14 days prior to the first dose&#xD;
               of study treatment.&#xD;
  &#xD;
           15. Active pulmonary tuberculosis&#xD;
  &#xD;
           16. Human immunodeficiency virus (HIV) infection, active hepatitis B infection, or&#xD;
               hepatitis C infection.&#xD;
  &#xD;
           17. Known hypersensitivity or allergy to IN10018, anti-PD-1/L1 monoclonal antibodies,&#xD;
               carboplatin or etoposide or to their drug components.&#xD;
  &#xD;
           18. Pregnant or lactating women or are expected to be pregnant or lactating during study&#xD;
               treatment.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>75 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Jun Zhao</last_name>
      <role>Principal Investigator</role>
      <affiliation>Peking University Cancer Hospital &amp; Institute</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Shu Fang</last_name>
      <phone>86-15933968623</phone>
      <email>shu.fang@inxmed.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Lily Li</last_name>
      <phone>86-13911551669</phone>
      <email>lily.li@inxmed.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Shandong Province Cancer Hospital</name>
        <address>
          <city>Jinan</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Yuping Sun</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Tianjin Medical University Cancer Institute &amp; Hospital</name>
        <address>
          <city>Tianjin</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Peng Chen</last_name>
      </contact>
    </location>
    <location>
      <facility>
        <name>Henan Provincial People's Hospital</name>
        <address>
          <city>Zhengzhou</city>
          <country>China</country>
        </address>
      </facility>
      <contact>
        <last_name>Shundong Cang</last_name>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>September 1, 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 10, 2023</last_update_submitted>
    <last_update_submitted_qc>September 10, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>First-line</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Lung Neoplasms</mesh_term>
      <mesh_term>Small Cell Lung Carcinoma</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carboplatin</mesh_term>
      <mesh_term>Etoposide</mesh_term>
      <mesh_term>Tislelizumab</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/NCT06030258
  org study id: IN10018-019
  nct id: NCT06030258
  lead sponsor: 
  is fda regulated drug: No
  is fda regulated device: No
  This is a multicenter, open-label, Randomized, phase Ib/II clinical study to evaluate the
        anti-tumor efficacy, safety, tolerability, and PK of IN10018 in combination with anti-PD-1/L1
        monoclonal antibody (Tislelizumab is proposed as the combination drug) and chemotherapy
        (platinum and etoposide) as the first-line treatment in Extensive-stage small cell lung
        cancer (ES-SCLC).
  This study consists of 2 parts: 1) Phase Ib-Dose Confirmation part: To assess the PK
        parameters, safety and recommended phase II dose (RP2D) of IN10018 in combination with
        anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed as the combination drug), platinum
        (carboplatin is proposed as the combination drug) and etoposide as the first-line treatment
        in ES-SCLC. 2) Phase II-Dose Expansion part: To assess the antitumor efficacy, safety and
        tolerability in the experimental group of IN10018 in combination with Tislelizumab,
        carboplatin and etoposide as compared to the control group of Tislelizumab in combination
        with carboplatin and etoposide as the first-line treatment in ES-SCLC.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: To identify the Recommended phase II dose (RP2D) of IN10018 in combination with Tislelizumab, Carboplatin and Etoposide in first-line ES-SCLC.
  time frame: Up to 3 years
  description: Evaluate proportion of patients suffered with AEs defined as dose-limited toxicities (DLTs) per protocol; and RP2D will be determined per the incidence of AEs defined as DLTs.
  measure: Progress free survival (PFS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR based on RECIST 1.1
  time frame: Up to 3 years
  description: Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first.
  measure: PFS of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per investigator based on RECIST 1.1
  time frame: Up to 3 years
  description: Defined as the time from randomization to first documentation of disease progression or to death due to any cause, whichever comes first.
  measure: Objective response rate (ORR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1.
  time frame: Up to 3 years
  description: Defined as the proportion of subjects with complete response (CR) or partial response (PR).
  measure: Duration of objective response (DOR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1.
  time frame: Up to 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: Disease Control Rate (DCR) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC per BICR and investigator based on RECIST 1.1
  time frame: Up to 3 years
  description: Defined as the proportion of patients with CR, PR, or stable disease (SD).
  measure: Overall survival (OS) of IN10018 in combination with Tislelizumab, carboplatin and etoposide as compared to Tislelizumab in combination with carboplatin and etoposide in first-line ES-SCLC.
  time frame: Up to 3 years
  description: Defined as the time from randomization to the date of death due to any cause.
  measure: Number of patients with adverse event
  time frame: Up to 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: Up to 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: Up to 3 years
  description: Maximum concentration (Cmax)
  measure: PK: Ctrough of IN10018 following single dose administration and at steady state
  time frame: Up to 3 years
  description: Trough concentration (Ctrough)
  measure: PK: Tmax of IN10018 following single dose administration and at steady state
  time frame: Up to 3 years
  description: Time to Cmax (Tmax)
  measure: PK: t1/2 of IN10018 following single dose administration and at steady state
  time frame: Up to 3 years
  description: Elimination half-life (t1/2)
  measure: PK: CL/F of IN10018 following single dose administration and at steady state
  time frame: Up to 3 years
  description: apparent clearance (CL/F)
  measure: PK: Vd/F of IN10018 following single dose administration and at steady state
  time frame: Up to 3 years
  description: Apparent volume of distribution (Vd/F)
  arm group label: Experimental group
  arm group type: Experimental
  description: IN10018 in combination with Tislelizumab, carboplatin and etoposide as the first-line treatment in ES-SCLC.
  arm group label: Control group
  arm group type: Active Comparator
  description: Tislelizumab in combination with carboplatin and etoposide as the first-line treatment in ES-SCLC
  intervention type: Drug
  intervention name: IN10018
  description: orally taken once daily
  arm group label: Experimental group
  other name: BI 853520
  intervention type: Drug
  intervention name: Tislelizumab
  description: 200mg D1, Q3W, intravenously
  arm group label: Control group
  arm group label: Experimental group
  intervention type: Drug
  intervention name: Carboplatin
  description: AUC 5 mg/ml/min, D1, Q3W, intravenously
  arm group label: Control group
  arm group label: Experimental group
  intervention type: Drug
  intervention name: Etoposide
  description: Etoposide 100 mg/m2, D1-D3, Q3W, intravenously
  arm group label: Control group
  arm group label: Experimental group
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 75 Years
  healthy volunteers: No
  last name: Jun Zhao
  role: Principal Investigator
  affiliation: Peking University Cancer Hospital & Institute
  last name: Shu Fang
  phone: 86-15933968623
  email: shu.fang@inxmed.com
  last name: Lily Li
  phone: 86-13911551669
  email: lily.li@inxmed.com
  facility: 
  contact: 
  facility: 
  contact: 
  facility: 
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Lung Neoplasms
  mesh term: Small Cell Lung Carcinoma
  mesh term: Carboplatin
  mesh term: Etoposide
  mesh term: Tislelizumab