<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/NCT03240393</url>
  </required_header>
  <id_info>
    <org_study_id>CINC280A2202</org_study_id>
    <nct_id>NCT03240393</nct_id>
  </id_info>
  <brief_title>Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>Phase II Multicenter 3-cohort Study of Oral cMET Inhibitor INC280 in Chinese Patients With EGFR Wild-type Advanced Non-small Cell Lung Cancer (NSCLC) Who Have Received 1 or 2 Prior Lines of Systemic Therapy for Advanced/Metastatic Disease</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Novartis Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Novartis</source>
  <oversight_info>
    <has_dmc>No</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>
      A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult&#xD;
      Chinese patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) who have&#xD;
      received one or two prior lines of systemic therapy for advanced/metastatic disease as&#xD;
      measured by overall response rate (ORR). The study will also evaluate safety and&#xD;
      pharmacokinetics of INC280.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Company Decision&#xD;
  </why_stopped>
  <start_date type="Anticipated">July 31, 2018</start_date>
  <completion_date type="Anticipated">October 26, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 26, 2021</primary_completion_date>
  <phase>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>ORR based on Central Radiology review/assessment (BIRC)</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) by BIRC - Key Secondary</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ORR by Investigator</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR) by investigator</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>DOR per RECIST 1.1 by investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR) by BIRC</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>TTR per RECIST 1.1 by BIRC assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Response (TTR) by investigator</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>TTR per RECIST 1.1 by investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) by BIRC</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>DCR per RECIST 1.1 by BIRC assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR) by investigator</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>DCR per RECIST 1.1 by investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) by BIRC</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>PFS per RECIST 1.1 by BIRC assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) by investigator</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>PFS per RECIST 1.1 by investigator assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>at least 18 weeks</time_frame>
    <description>OS, defined as time from first dose of INC280 to death due to any cause</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax profile of INC280</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pharmacokinetics of INC280</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmax profile of INC280 metabolite CMN288</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pharmacokinetics of INC280 metabolite CMN288</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin profile of INC280</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pharmacokinetics of INC280</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cmin profile of INC280 metabolite CMN288</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pharmacokinetics of INC280 metabolite CMN288</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration-time profiles of INC280</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pharmacokinetics of INC280</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Plasma concentration-time profiles of INC280 metabolite CMN288</measure>
    <time_frame>6 weeks</time_frame>
    <description>Pharmacokinetics of INC280 metabolite CMN288</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Carcinoma</condition>
  <condition>Non-Small-Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>cMET GCN ≥ 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cMET GCN ≥ 4 and &lt; 6</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-treated patients with cMET GCN ≥ 4 and &lt; 6 treated with INC280 at 400 mgBID</description>
  </arm_group>
  <arm_group>
    <arm_group_label>cMET mutations</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INC280</intervention_name>
    <description>cMET GCN ≥ 6 cMET GCN ≥ 4 and &lt; 6 cMET mutations</description>
    <arm_group_label>cMET GCN ≥ 4 and &lt; 6</arm_group_label>
    <arm_group_label>cMET GCN ≥ 6</arm_group_label>
    <arm_group_label>cMET mutations</arm_group_label>
    <other_name>capmatinib</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Stage IIIB or IV NSCLC (any histology) at the time of study entry&#xD;
&#xD;
          -  Histologically or cytologically confirmed diagnosis of NSCLC that is:&#xD;
&#xD;
               1. EGFR wt as per patient standard of care by a validated test&#xD;
&#xD;
               2. AND ALK-negative rearrangement as part of the patient standard of care by a&#xD;
                  validated test&#xD;
&#xD;
               3. AND (by central assessment) either:&#xD;
&#xD;
                    -  Cohort 1: Pre-treated patients with cMET GCN ≥ 6 or&#xD;
&#xD;
                    -  Cohort 2: Pre-treated patients with cMET GCN ≥4 and &lt; 6, or&#xD;
&#xD;
                    -  Cohort 3: Pre-treated patients with cMET mutations regardless of cMET GCN,&#xD;
                       or&#xD;
&#xD;
          -  Patients must have failed one or two prior lines of systemic therapy for&#xD;
             advanced/metastatic disease&#xD;
&#xD;
          -  At least one measurable lesion as defined by RECIST 1.1&#xD;
&#xD;
          -  Patients must have recovered from all toxicities related to prior anticancer therapies&#xD;
             to grade ≤ 1 (CTCAE v 4.03). Patients with any grade of alopecia are allowed to enter&#xD;
             the study.&#xD;
&#xD;
          -  Patients must have adequate organ function&#xD;
&#xD;
          -  ECOG performance status (PS) of 0 or 1&#xD;
&#xD;
        Details and other protocol-defined inclusion criteria may apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with crizotinib, or any other cMET or HGF inhibitor&#xD;
&#xD;
          -  Patients with characterized EGFR mutations that predict sensitivity to EGFR therapy,&#xD;
             including, but not limited to exon 19 deletions and exon 21 mutations&#xD;
&#xD;
          -  Patients with characterized ALK-positive rearrangement&#xD;
&#xD;
          -  Clinically significant, uncontrolled heart diseases.&#xD;
&#xD;
          -  Patients receiving treatment with medications that cannot be discontinued at least 1&#xD;
             week prior to first INC280 treatment and for the duration of the study:&#xD;
&#xD;
               -  Strong and moderate inhibitors of CYP3A4&#xD;
&#xD;
               -  Strong inducers of CYP3A4&#xD;
&#xD;
          -  Impairment of GI function or GI disease that may significantly alter the absorption of&#xD;
             INC280&#xD;
&#xD;
          -  Patients receiving treatment with any enzyme-inducing anticonvulsant&#xD;
&#xD;
          -  Previous anti-cancer and investigational agents within 4 weeks or ≤ 5 x half-life of&#xD;
             the agent (whichever is longer) before first dose&#xD;
&#xD;
          -  Pregnant or nursing women&#xD;
&#xD;
          -  Women of child-bearing potential, unless they are using highly effective methods of&#xD;
             contraception&#xD;
&#xD;
          -  Sexually active males unless they use a condom during intercourse&#xD;
&#xD;
        Other protocol-defined exclusion criteria may apply&#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>Novartis Pharmaceuticals</last_name>
    <role>Study Director</role>
    <affiliation>Novartis Pharmaceuticals</affiliation>
  </overall_official>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>July 26, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <last_update_submitted>July 24, 2018</last_update_submitted>
  <last_update_submitted_qc>July 24, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">July 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non Small Cell Lung Cancer</keyword>
  <keyword>NSCLC</keyword>
  <keyword>INC280</keyword>
  <keyword>EGFR wild-type (wt)</keyword>
  <keyword>advanced non-small cell lung cancer</keyword>
  <keyword>advanced/metastatic disease</keyword>
  <keyword>Non-small cell lung carcinoma (NSCLC)</keyword>
  <keyword>treatment of lung cancer after first metastasis</keyword>
  <keyword>lung cancer</keyword>
  <keyword>lung adenocarcinoma</keyword>
  <keyword>Non small cell lung carcinoma</keyword>
  <keyword>Non-small cell lung cancer</keyword>
  <keyword>MET exon 14 deletion</keyword>
  <keyword>MET exon 14 skipping</keyword>
  <keyword>MET exon 14 mutation</keyword>
  <keyword>MET mutation</keyword>
  <keyword>MET amplification</keyword>
  <keyword>MET inhibitor</keyword>
  <keyword>MET dysregulation</keyword>
  <keyword>MET activation</keyword>
  <keyword>MET signaling</keyword>
  <keyword>MET pathway</keyword>
  <keyword>MET</keyword>
  <keyword>cMET</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Planned Shared Data Description: Copy and paste this Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.&#xD;
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03240393
org study id: CINC280A2202
nct id: NCT03240393
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
A phase II study to evaluate antitumor activity of oral cMET inhibitor INC280 in adult
      Chinese patients with EGFR wild-type, advanced non-small cell lung cancer (NSCLC) who have
      received one or two prior lines of systemic therapy for advanced/metastatic disease as
      measured by overall response rate (ORR). The study will also evaluate safety and
      pharmacokinetics of INC280.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: ORR based on Central Radiology review/assessment (BIRC)
time frame: at least 18 weeks
description: Proportion of patients with a best overall response defined as complete response (CR) or partial response (PR) by Blinded Independent Review Committee (BIRC) assessment per RECIST 1.1
measure: Duration of Response (DOR) by BIRC - Key Secondary
time frame: at least 18 weeks
description: Calculated as the time from the date of the first documented CR or PR by Blinded Independent Review Committee (BIRC) per RECIST 1.1 to the first documented progression or death due to any cause for patients with PR or CR.
measure: ORR by Investigator
time frame: at least 18 weeks
description: ORR (complete response (CR)+ partial response (PR)) per RECIST 1.1 by investigator assessment
measure: Duration of Response (DOR) by investigator
time frame: at least 18 weeks
description: DOR per RECIST 1.1 by investigator assessment
measure: Time to Response (TTR) by BIRC
time frame: at least 18 weeks
description: TTR per RECIST 1.1 by BIRC assessment
measure: Time to Response (TTR) by investigator
time frame: at least 18 weeks
description: TTR per RECIST 1.1 by investigator assessment
measure: Disease Control Rate (DCR) by BIRC
time frame: at least 18 weeks
description: DCR per RECIST 1.1 by BIRC assessment
measure: Disease Control Rate (DCR) by investigator
time frame: at least 18 weeks
description: DCR per RECIST 1.1 by investigator assessment
measure: Progression-free Survival (PFS) by BIRC
time frame: at least 18 weeks
description: PFS per RECIST 1.1 by BIRC assessment
measure: Progression-free Survival (PFS) by investigator
time frame: at least 18 weeks
description: PFS per RECIST 1.1 by investigator assessment
measure: Overall Survival (OS)
time frame: at least 18 weeks
description: OS, defined as time from first dose of INC280 to death due to any cause
measure: Cmax profile of INC280
time frame: 6 weeks
description: Pharmacokinetics of INC280
measure: Cmax profile of INC280 metabolite CMN288
time frame: 6 weeks
description: Pharmacokinetics of INC280 metabolite CMN288
measure: Cmin profile of INC280
time frame: 6 weeks
description: Pharmacokinetics of INC280
measure: Cmin profile of INC280 metabolite CMN288
time frame: 6 weeks
description: Pharmacokinetics of INC280 metabolite CMN288
measure: Plasma concentration-time profiles of INC280
time frame: 6 weeks
description: Pharmacokinetics of INC280
measure: Plasma concentration-time profiles of INC280 metabolite CMN288
time frame: 6 weeks
description: Pharmacokinetics of INC280 metabolite CMN288
arm group label: cMET GCN ≥ 6
arm group type: Experimental
description: Pre-treated patients with cMET GCN ≥ 6 treated with INC280 at 400mg BID
arm group label: cMET GCN ≥ 4 and < 6
arm group type: Experimental
description: Pre-treated patients with cMET GCN ≥ 4 and < 6 treated with INC280 at 400 mgBID
arm group label: cMET mutations
arm group type: Experimental
description: Pre-treated patients with cMET mutations regardless of cMET GCN treated with INC280 at 400mg BID
intervention type: Drug
intervention name: INC280
description: cMET GCN ≥ 6 cMET GCN ≥ 4 and < 6 cMET mutations
arm group label: cMET GCN ≥ 4 and < 6
arm group label: cMET GCN ≥ 6
arm group label: cMET mutations
other name: capmatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Novartis Pharmaceuticals
role: Study Director
affiliation: Novartis Pharmaceuticals
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
sharing ipd: Undecided
ipd description: Planned Shared Data Description: Copy and paste this Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.
This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com