<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/NCT02191891</url>
  </required_header>
  <id_info>
    <org_study_id>1280.16</org_study_id>
    <nct_id>NCT02191891</nct_id>
  </id_info>
  <brief_title>Xentuzumab (BI 836845) Plus Afatinib in Patients With Epidermal Growth Factor Receptor (EGFR) Mutant Non-small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>A Phase Ib Open-label Clinical Trial of Once Daily Oral Treatment of Afatinib Plus Weekly Intravenous Infusion of Xentuzumab (BI 836845) in Patients With EGFR Mutant Non-small Cell Lung Cancer With Progression Following Prior EGFR Tyrosine Kinase Inhibitors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</source>
  <brief_summary>
    <textblock>
      Part A: To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D)&#xD;
      of Xentuzumab (BI 836845) in combination with afatinib in patients with non-small cell lung&#xD;
      cancer with progression following prior treatment (EGFR TKI or platinum-based chemotherapy).&#xD;
&#xD;
      Part B: To evaluate the early anti-tumour activity of Xentuzumab (BI 836845) in combination&#xD;
      with afatinib in patients with EGFR mutant non-small cell lung cancer with progression&#xD;
      following prior irreversible EGFR TKIs.&#xD;
&#xD;
      Part A and B: To evaluate the safety and pharmacokinetics of BI 836845 in combination with&#xD;
      afatinib in patients with non-small cell lung cancer&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 21, 2014</start_date>
  <completion_date type="Actual">April 18, 2018</completion_date>
  <primary_completion_date type="Actual">April 18, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) of BI 836845 in combination with afatinib - part A</measure>
    <time_frame>up to 12 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Dose limiting toxicity (DLT) during the first treatment course - part A</measure>
    <time_frame>up to 28 days</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response (OR), defined as complete response (CR) or partial response (PR)</measure>
    <time_frame>up to 12 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Disease control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD)</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to objective response, defined as the duration of time from the date of first treatment administration until objective response</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of objective response, defined as the duration of time from first objective response to the date of first objective tumour progression or death due to any cause</measure>
    <time_frame>up to 12 months</time_frame>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">32</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <arm_group>
    <arm_group_label>BI 836845 + afatinib</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>BI 836845 low or high dose (weekly IV infusion), afatinib 30mg or 40mg (once daily oral dosing)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 836845</intervention_name>
    <description>Human monoclonal antibody. Two dose levels (high or low) depending on the dose cohort explored</description>
    <arm_group_label>BI 836845 + afatinib</arm_group_label>
    <other_name>Xentuzumab</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>afatinib</intervention_name>
    <description>Irreversible EGFR tyrosine kinase inhibitor. Two dose levels (30 mg, 40 mg) depending on the dose cohort explored or determined dose at part A</description>
    <arm_group_label>BI 836845 + afatinib</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Aged 18 years or older&#xD;
&#xD;
          -  Pathologically confirmed of advanced and/or metastatic stage IIIb/IV non-small cell&#xD;
             carcinoma of lung&#xD;
&#xD;
          -  Activating EGFR mutation (exon 19 deletion, L858R, G719X, L861X)&#xD;
&#xD;
          -  Presence of EGFR activating mutation and absence of EGFR T790M in the tumour&#xD;
             associated with the latest disease progression. Only applicable in Part B&#xD;
&#xD;
          -  Must have adequate fresh or archival tumour tissue at the late disease progression&#xD;
             immediately prior to the study entry&#xD;
&#xD;
          -  Part A: Progression of disease (RECIST 1.1) while on continuous treatment with single&#xD;
             EGFR TKI or for histology other than adenocarcinoma and without prior EGFR TKI&#xD;
             treatment: progression of disease (RECIST v1.1) on platinum-based chemotherapy. Part&#xD;
             B: Progression of disease (RECIST v1.1) while on continuous treatment with single&#xD;
             agent of the second generation irreversible EGFR TKI (e.g. afatinib or dacomitinib)&#xD;
&#xD;
          -  No intervening systemic therapy between cessation of EGFR TKI and study treatment&#xD;
&#xD;
          -  Patient must have measurable disease per RECIST 1.1 presented after tumour biopsy for&#xD;
             the late disease progression&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance score 0 or 1&#xD;
&#xD;
          -  Life expectancy of &gt;= 3 months&#xD;
&#xD;
          -  Fasting plasma glucose &lt; 8.9 mmol/L (&lt; 160mg/dL) and HbA1C &lt; 8%&#xD;
&#xD;
          -  Adequate organ function&#xD;
&#xD;
          -  Recovered from any previous therapy related toxicity to &lt;= Grade 1 at study entry&#xD;
             (except for stable sensory neuropathy &lt;= Grade 2 and alopecia)&#xD;
&#xD;
          -  Written informed consent that is consistent with ICH-GCP guidelines and local&#xD;
             regulations&#xD;
&#xD;
          -  No known potentially targetable mutation other than IGF signaling pathway or EGFR or&#xD;
             no available treatment for potentially targetable mutation&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Part A only: For patient who has been treated with afatinib: last treatment at reduced&#xD;
             dose below the assigned dose level&#xD;
&#xD;
          -  Patient whose disease progressed on insufficient dose of EGFR TKI immediately prior to&#xD;
             study in the opinion of the investigator&#xD;
&#xD;
          -  More than 2 prior EGFR TKI treatment regimens for Part B&#xD;
&#xD;
          -  Chemotherapy, biological therapy or investigational agents (except EGFR TKIs) within 4&#xD;
             weeks&#xD;
&#xD;
          -  Use of previous EGFR TKIs except afatinib within 3 days&#xD;
&#xD;
          -  Radiotherapy within 4 weeks prior to the start of study treatment&#xD;
&#xD;
          -  Active brain or subdural metastases&#xD;
&#xD;
          -  Meningeal carcinomatosis.&#xD;
&#xD;
          -  Major surgery (as judged by the investigator) within 4 weeks&#xD;
&#xD;
          -  Known hypersensitivity to afatinib, monoclonal antibody&#xD;
&#xD;
          -  Prior severe infusion-related reaction to a monoclonal antibody&#xD;
&#xD;
          -  History or presence of clinically relevant cardiovascular abnormalities&#xD;
&#xD;
          -  Female patients of childbearing potential (see Section 4.2.2.3) and male who are able&#xD;
             to father a child&#xD;
&#xD;
          -  Any history of or concomitant condition that, in the opinion of the investigator not&#xD;
             to comply with the study or interfere with the evaluation of the efficacy and safety&#xD;
             of the test drug&#xD;
&#xD;
          -  Previous or concomitant malignancies at other sites, except effectively treated&#xD;
             non-melanoma skin cancers, carcinoma in situ of the cervix, ductal carcinoma in situ&#xD;
             or effectively treated malignancy that has been in remission for more than 3 years and&#xD;
             is considered to be cured.&#xD;
&#xD;
          -  Disease that is considered by the investigator to be rapidly progressing or life&#xD;
             threatening such as extensive symptomatic visceral disease including hepatic&#xD;
             involvement and pulmonary lymphangitic spread of tumour (subjects who are intended for&#xD;
             urgent chemotherapy)&#xD;
&#xD;
          -  Requiring treatment with any of the prohibited concomitant medications&#xD;
&#xD;
          -  Known pre-existing interstitial lung disease (ILD)&#xD;
&#xD;
          -  Any history or presence of poorly controlled gastrointestinal disorders that could&#xD;
             affect the absorption of the study drug&#xD;
&#xD;
          -  Active hepatitis B infection active hepatitis C infection and/or known HIV carrier.&#xD;
&#xD;
          -  Previous treatment with agents targeting the insulin like growth factor (IGF)&#xD;
             signalling pathway.&#xD;
&#xD;
          -  Previous treatment with EGFR TKI which cannot be documented as either reversible or&#xD;
             irreversible (Part B only)&#xD;
&#xD;
          -  Part B only: Prior treatment with third generation irreversible EGFR TKI (e.g. AZD9291&#xD;
             or CO-1686)&#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>Boehringer Ingelheim</last_name>
    <role>Study Chair</role>
    <affiliation>Boehringer Ingelheim</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>National Hospital Organization Kyushu Cancer Center</name>
      <address>
        <city>Fukuoka, Fukuoka</city>
        <zip>811-1395</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chungbuk National University Hospital</name>
      <address>
        <city>Cheongju</city>
        <zip>361-771</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>120-752</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>135-710</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>138-736</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Centre</name>
      <address>
        <city>Singapore</city>
        <zip>169610</zip>
        <country>Singapore</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Gung Memorial Hospital Chiayi</name>
      <address>
        <city>Chiayi</city>
        <zip>613</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Chang Gung Memorial Hospital</name>
      <address>
        <city>Kaohsiung</city>
        <zip>83301</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NCKUH</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Singapore</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>April 2018</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 14, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 16, 2014</study_first_posted>
  <last_update_submitted>April 30, 2018</last_update_submitted>
  <last_update_submitted_qc>April 30, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 1, 2018</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>Carcinoma, Non-Small-Cell Lung</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Afatinib</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02191891
org study id: 1280.16
nct id: NCT02191891
lead sponsor: 
Part A: To determine the maximum tolerated dose (MTD) and/or recommended phase II dose (RP2D)
      of Xentuzumab (BI 836845) in combination with afatinib in patients with non-small cell lung
      cancer with progression following prior treatment (EGFR TKI or platinum-based chemotherapy).

      Part B: To evaluate the early anti-tumour activity of Xentuzumab (BI 836845) in combination
      with afatinib in patients with EGFR mutant non-small cell lung cancer with progression
      following prior irreversible EGFR TKIs.

      Part A and B: To evaluate the safety and pharmacokinetics of BI 836845 in combination with
      afatinib in patients with non-small cell lung cancer
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD) of BI 836845 in combination with afatinib - part A
time frame: up to 12 months
measure: Dose limiting toxicity (DLT) during the first treatment course - part A
time frame: up to 28 days
measure: Objective response (OR), defined as complete response (CR) or partial response (PR)
time frame: up to 12 months
measure: Disease control (DC), defined as complete response (CR), partial response (PR) or stable disease (SD)
time frame: up to 12 months
measure: Time to objective response, defined as the duration of time from the date of first treatment administration until objective response
time frame: up to 12 months
measure: Duration of objective response, defined as the duration of time from first objective response to the date of first objective tumour progression or death due to any cause
time frame: up to 12 months
arm group label: BI 836845 + afatinib
arm group type: Experimental
description: BI 836845 low or high dose (weekly IV infusion), afatinib 30mg or 40mg (once daily oral dosing)
intervention type: Drug
intervention name: BI 836845
description: Human monoclonal antibody. Two dose levels (high or low) depending on the dose cohort explored
arm group label: BI 836845 + afatinib
other name: Xentuzumab
intervention type: Drug
intervention name: afatinib
description: Irreversible EGFR tyrosine kinase inhibitor. Two dose levels (30 mg, 40 mg) depending on the dose cohort explored or determined dose at part A
arm group label: BI 836845 + afatinib
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
role: Study Chair
affiliation: Boehringer Ingelheim
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
country: Korea, Republic of
country: Singapore
country: Taiwan
responsible party type: Sponsor
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Afatinib