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/NCT05982522</url>
    </required_header>
    <id_info>
      <org_study_id>IN10018-017</org_study_id>
      <nct_id>NCT05982522</nct_id>
    </id_info>
    <brief_title>IN10018 Combination Therapy in Previously-treated Solid Tumors</brief_title>
    <official_title>A Multicenter, Open-Label, Randomized, Phase Ib/II Clinical Trial to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of IN10018 Combined With Taxane and Anti-PD-1/L1 Monoclonal Antibody in Previously-treated Solid Tumors</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 phase Ib/II, randomized, open-label, multicenter clinical trial to evaluate the&#xD;
        antitumor activities, safety, tolerability and pharmacokinetics (PK) of IN10018 in&#xD;
        combination with taxane and anti-PD-1/L1 monoclonal antibody in patients with locally&#xD;
        advanced or metastatic solid tumors who have failed in or been intolerant to at least one&#xD;
        line of standard therapy. This study will be firstly carried out in previously-treated&#xD;
        non-small cell lung cancer (NSCLC) population,&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This study consists of 2 parts: 1) Phase Ib-Dose Confirmation part: To assess the safety and&#xD;
        recommended phase II dose (RP2D) of IN10018 in combination with taxane (nab-paclitaxel is&#xD;
        proposed) and anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed) in&#xD;
        previously-treated solid tumors. 2) Phase II-Dose Expansion part: To assess the antitumor&#xD;
        efficacy and safety of IN10018+nab-paclitaxel+Tislelizumab as compared to&#xD;
        nab-paclitaxel+Tislelizumab in previously-treated solid tumors. This study will be firstly&#xD;
        carried out in previously-treated NSCLC population, and after getting enough efficacy and&#xD;
        safety data of IN10018+nab-paclitaxel+Tislelizumab in NSCLC population and also taken into&#xD;
        consideration of disease background of other specific solid tumors, sponsor will decide if to&#xD;
        expand the treatment regimen into other solid tumors.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 2023</start_date>
    <completion_date type="Anticipated">July 2026</completion_date>
    <primary_completion_date type="Anticipated">December 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>Recommended phase II dose (RP2D) of IN10018 in combination with nab-paclitaxel and Tislelizumab</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 nab-paclitaxel and Tislelizumab.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Objective response rate (ORR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per blinded independent central review (BICR) based on RECIST 1.1</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>
    <secondary_outcome>
      <measure>Progression-free survival (PFS) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per BICR and investigators based on RECIST 1.1</measure>
      <time_frame>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>Duration of objective response (DOR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per BICR and investigators based on RECIST 1.1</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>Disease Control Rate (DCR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per BICR and investigators based on RECIST 1.1.</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>Objective response rate (ORR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per investigators based on RECIST 1.1.</measure>
      <time_frame>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>Overall survival (OS) in IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors.</measure>
      <time_frame>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>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">72</enrollment>
    <condition>Solid Tumor</condition>
    <arm_group>
      <arm_group_label>Experimental Group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>IN10018 + nab-paclitaxel + Tislelizumab in previously-treated NSCLC</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Control Group</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Nab-paclitaxel + Tislelizumab in previously-treated NSCLC</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>Nab-paclitaxel</intervention_name>
      <description>125 mg/m2 D1, 8 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>Tislelizumab</intervention_name>
      <description>200mg 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 or cytologically confirmed NSCLC, which is not suitable for locallly&#xD;
               radical therapy.&#xD;
  &#xD;
               Note: Subjects should have received prior platinum-based doublet chemotherapy and&#xD;
               anti-PD-1/L1-based systemic therapy and failed in treatment.&#xD;
  &#xD;
            4. Subjects who have failed in 1- to 2 prior lines of standard systemic therapy.&#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.&#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. Previously documented EGFR, ALK and ROS1 mutation.&#xD;
  &#xD;
            2. Have received chemotherapy, biological therapy, endocrine therapy, immunotherapy and&#xD;
               other antitumor drugs within 4 weeks prior to the first dose of study treatment.&#xD;
  &#xD;
            3. Have received other antitumor investigational drugs or treatments within 4 weeks prior&#xD;
               to the first dose of study treatment.&#xD;
  &#xD;
            4. Have received radiotherapy within 14 days prior to the first dose of study treatment.&#xD;
  &#xD;
            5. Have had allogeneic haematopoietic stem cell transplantation or organ transplantation.&#xD;
  &#xD;
            6. History of autoimmune disease within the past 2 years.&#xD;
  &#xD;
            7. 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.&#xD;
  &#xD;
            8. Currently have interstitial pneumonitis.&#xD;
  &#xD;
            9. Have had FAK inhibitors treatment.&#xD;
  &#xD;
           10. Have received prior nab-paclitaxel treatment and the first documented disease&#xD;
               progression/recurrence is within 6 months since the last dose of nab-paclitaxel&#xD;
               treatment.&#xD;
  &#xD;
           11. Malignancies other than the study disease within 3 years prior to the first dose of&#xD;
               study treatment.&#xD;
  &#xD;
           12. Active central nervous system (CNS) metastases and/or carcinogenic meningitis.&#xD;
  &#xD;
           13. Has a history of severe cardiovascular or cerebrovascular diseases within 6 months&#xD;
               prior to the first dose.&#xD;
  &#xD;
           14. Pleural, pericardial or abdominal effusion that are clinically symptomatic and require&#xD;
               puncture or drainage.&#xD;
  &#xD;
           15. Any active infection requiring systemic therapy within 14 days prior to the first dose&#xD;
               of study treatment.&#xD;
  &#xD;
           16. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
               that might confound the results of the study. Note: Subjects who have experienced&#xD;
               Grade ≥ 3 immuno-related AEs (irAEs) during prior immunotherapy will not be enrolled.&#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>Jifeng Feng</last_name>
      <role>Principal Investigator</role>
      <affiliation>Jiangsu Province Cancer Hosipital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Bohong Zhang</last_name>
      <phone>+86 18801955197</phone>
      <email>bohong.zhang@inxmed.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 13, 2023</study_first_submitted>
    <study_first_submitted_qc>August 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 1, 2023</last_update_submitted>
    <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Paclitaxel</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/NCT05982522
  org study id: IN10018-017
  nct id: NCT05982522
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  This is a phase Ib/II, randomized, open-label, multicenter clinical trial to evaluate the
        antitumor activities, safety, tolerability and pharmacokinetics (PK) of IN10018 in
        combination with taxane and anti-PD-1/L1 monoclonal antibody in patients with locally
        advanced or metastatic solid tumors who have failed in or been intolerant to at least one
        line of standard therapy. This study will be firstly carried out in previously-treated
        non-small cell lung cancer (NSCLC) population,
  This study consists of 2 parts: 1) Phase Ib-Dose Confirmation part: To assess the safety and
        recommended phase II dose (RP2D) of IN10018 in combination with taxane (nab-paclitaxel is
        proposed) and anti-PD-1/L1 monoclonal antibody (Tislelizumab is proposed) in
        previously-treated solid tumors. 2) Phase II-Dose Expansion part: To assess the antitumor
        efficacy and safety of IN10018+nab-paclitaxel+Tislelizumab as compared to
        nab-paclitaxel+Tislelizumab in previously-treated solid tumors. This study will be firstly
        carried out in previously-treated NSCLC population, and after getting enough efficacy and
        safety data of IN10018+nab-paclitaxel+Tislelizumab in NSCLC population and also taken into
        consideration of disease background of other specific solid tumors, sponsor will decide if to
        expand the treatment regimen into other solid tumors.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Recommended phase II dose (RP2D) of IN10018 in combination with nab-paclitaxel and Tislelizumab
  time frame: 3 years
  description: Evaluate the number of patients with dose-limited toxicities (DLTs); Determine the RP2D of IN10018 in combination with nab-paclitaxel and Tislelizumab.
  measure: Objective response rate (ORR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per blinded independent central review (BICR) based on RECIST 1.1
  time frame: 3 years
  description: Defined as the proportion of subjects with complete response (CR) or partial response (PR)
  measure: Progression-free survival (PFS) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per BICR and investigators based on RECIST 1.1
  time frame: 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: Duration of objective response (DOR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per BICR and investigators based on RECIST 1.1
  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: Disease Control Rate (DCR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per BICR and investigators based on RECIST 1.1.
  time frame: 3 years
  description: Defined as the proportion of patients with CR, PR, or stable disease (SD).
  measure: Objective response rate (ORR) of IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors per investigators based on RECIST 1.1.
  time frame: 3 years
  description: Defined as the proportion of subjects with complete response (CR) or partial response (PR).
  measure: Overall survival (OS) in IN10018+nab-paclitaxel+Tislelizumab as compared to nab-paclitaxel+Tislelizumab in previously-treated solid tumors.
  time frame: 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: 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
  arm group type: Experimental
  description: IN10018 + nab-paclitaxel + Tislelizumab in previously-treated NSCLC
  arm group label: Control Group
  arm group type: Active Comparator
  description: Nab-paclitaxel + Tislelizumab in previously-treated NSCLC
  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: Nab-paclitaxel
  description: 125 mg/m2 D1, 8 Q3W, Intravenously
  arm group label: Control Group
  arm group label: Experimental Group
  intervention type: Drug
  intervention name: Tislelizumab
  description: 200mg 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: Jifeng Feng
  role: Principal Investigator
  affiliation: Jiangsu Province Cancer Hosipital
  last name: Bohong Zhang
  phone: +86 18801955197
  email: bohong.zhang@inxmed.com
  responsible party type: Sponsor
  mesh term: Neoplasms
  mesh term: Paclitaxel
  mesh term: Tislelizumab