<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/NCT03780725</url>
  </required_header>
  <id_info>
    <org_study_id>1381-0003</org_study_id>
    <secondary_id>2017-005046-30</secondary_id>
    <nct_id>NCT03780725</nct_id>
  </id_info>
  <brief_title>This Study Tests How BI 754111 is Distributed in Patients With Advanced Non-small Cell Lung Cancer or Patients With Head and Neck Cancer Who Are Treated With BI 754091</brief_title>
  <official_title>An Open Label Phase I PET Imaging Study to Investigate the Bio-distribution and Tumor Uptake of [89Zr]Zr-BI 754111 in Patients With Advanced Non-small Cell Lung Cancer and Head and Neck Squamous Cell Carcinoma Treated With BI 754111 in Combination With BI 754091</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boehringer Ingelheim</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Boehringer Ingelheim</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>
      The main objective of this study is to determine the biodistribution and intra-tumor&#xD;
      accumulation of [89Zr]Zr-BI 754111 at baseline and its change upon treatment&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to company decision.&#xD;
  </why_stopped>
  <start_date type="Actual">January 22, 2019</start_date>
  <completion_date type="Actual">December 8, 2020</completion_date>
  <primary_completion_date type="Actual">February 19, 2020</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>The trial is divided in 2 Parts and will be conducted in a staggered approach, i.e. Part 2 follows Part 1. Part 2 will be initiated following a positive decision of the Study Monitoring Committee (SMC) after reviewing of all available data from Part 1 in order to assess whether a blockade of [89Zr]Zr-BI 754111 will be demonstrated.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Standardized uptake values (SUVs) of [89Zr]Zr-BI 754111 for tumor uptake</measure>
    <time_frame>Up to 29 days post-baseline</time_frame>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">8</enrollment>
  <condition>Carcinoma, Non-Small-Cell Lung</condition>
  <condition>Head and Neck Neoplasms</condition>
  <arm_group>
    <arm_group_label>Part 1: Ezabenlimab 240mg + BI 754111 600mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2: Ezabenlimab 240mg + BI 754111 40mg</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 754111</intervention_name>
    <description>Solution for infusion</description>
    <arm_group_label>Part 1: Ezabenlimab 240mg + BI 754111 600mg</arm_group_label>
    <arm_group_label>Part 2: Ezabenlimab 240mg + BI 754111 40mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>[89Zr]Zr-BI 754111</intervention_name>
    <description>Solution for infusion</description>
    <arm_group_label>Part 1: Ezabenlimab 240mg + BI 754111 600mg</arm_group_label>
    <arm_group_label>Part 2: Ezabenlimab 240mg + BI 754111 40mg</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 754091</intervention_name>
    <description>Solution for infusion</description>
    <arm_group_label>Part 1: Ezabenlimab 240mg + BI 754111 600mg</arm_group_label>
    <arm_group_label>Part 2: Ezabenlimab 240mg + BI 754111 40mg</arm_group_label>
    <other_name>Ezabenlimab</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Provision of signed and dated, written Informed Consent Form (ICF) prior to any trial&#xD;
             specific procedures, sampling, or analyses&#xD;
&#xD;
          -  Patients of legal age (according to local legislation) at the time of signature of the&#xD;
             ICF&#xD;
&#xD;
          -  Patients with histologically confirmed diagnosis of recurrent NSCLC who received anti-&#xD;
             PD-1 or anti PD-L1 as Part of last treatment with at least 3 months of stable disease&#xD;
             (i.e.patients with confirmed response (PR or CR) regardless of duration of response or&#xD;
             stable disease (SD) for a minimum of 3 months) and have become refractory to anti-PD-&#xD;
             1/ anti-PD-L1 based treatment OR&#xD;
&#xD;
             --Patients with histologically confirmed diagnosis of recurrent metastatic HNSCC who&#xD;
             progressed after platinum based therapy or not indicated for receiving standard&#xD;
             (radio) chemotherapy (previous treatment with anti- PD-1/ PD-L1 is allowed)&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG, R01-0787) score: 0 to 1&#xD;
&#xD;
          -  Patient must have at least one PET imageable and evaluable tumor lesion of 20mm&#xD;
&#xD;
          -  Patients must have at least one tumor lesion amenable to biopsy. This lesion should be&#xD;
             PET imageable and evaluable as defined above and the biopsy should be obtained before&#xD;
             first BI 754091 administration, unless medically contra-indicated. In the latter case,&#xD;
             25 4μm sections from an archival biopsy taken at relapse after the previous treatment&#xD;
             are acceptable&#xD;
&#xD;
          -  Must have evaluable lesion(s) according to Revised Response Evaluation Criteria in&#xD;
             Solid Tumors (RECIST) Version 1.1 and iRECIST&#xD;
&#xD;
          -  Life expectancy of at least 12 weeks after the start of the treatment according to the&#xD;
             Investigator's judgement&#xD;
&#xD;
          -  Male or female patients. Women of childbearing potential (WOCBP)1 and men able to&#xD;
             father a child must be ready and able to use highly effective methods of birth control&#xD;
             per International Conference on Harmonisation (ICH) M3 (R2) (that result in a low&#xD;
             failure rate of less than 1% per year when used consistently and correctly) during&#xD;
             trial Participation and for at least 6 months after the last administration of trial&#xD;
             medication. A list of contraception methods meeting these criteria is provided in the&#xD;
             patient information.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not having fully recovered from major surgery before they enter into the trial&#xD;
             according to investigator judgment or planned for major surgery within 12 months after&#xD;
             screening, e.g. hip replacement&#xD;
&#xD;
          -  Patients who must or wish to continue the intake of restricted medications or any drug&#xD;
             considered likely to interfere with the safe conduct of the trial&#xD;
&#xD;
          -  Patients not expected to comply with the protocol requirements or not expected to&#xD;
             complete the trial as scheduled&#xD;
&#xD;
          -  Previous treatment in this trial&#xD;
&#xD;
          -  Any investigational or anti-tumor treatment within 4 weeks or within 5 half-life&#xD;
             periods (whichever is shorter) prior to the initiation of trial treatment.&#xD;
&#xD;
          -  Any unresolved toxicities from prior therapy greater than CTCAE Grade 1 at the time of&#xD;
             starting study treatment with the exception of alopecia and Grade 2 neuropathy due to&#xD;
             prior platinum-based therapy&#xD;
&#xD;
          -  Prior treatment with anti-LAG-3 agents&#xD;
&#xD;
          -  Presence of other active invasive cancers other than the one treated in this trial,&#xD;
             with the exception of resected/ablated basal or squamous-cell carcinoma of the skin or&#xD;
             carcinoma in situ of the cervix, or other local tumors considered cured by local&#xD;
             treatment&#xD;
&#xD;
          -  Untreated brain metastasis(es) that may be considered active. Patients with previously&#xD;
             treated brain metastases may Participate provided they are stable (i.e., without&#xD;
             evidence of PD by imaging for at least 4 weeks prior to the first dose of trial&#xD;
             treatment, and any neurologic symptoms have returned to baseline), and there is no&#xD;
             evidence of new or enlarging brain metastases&#xD;
&#xD;
          -  Inadequate organ function or bone marrow reserve as demonstrated by the laboratory&#xD;
             values&#xD;
&#xD;
          -  Any of the following cardiac criteria:&#xD;
&#xD;
               -  Mean resting corrected QT interval (QTc) &gt;470 msec&#xD;
&#xD;
               -  Any clinically important abnormalities in rhythm, conduction, or morphology of&#xD;
                  resting ECGs, e.g., complete left bundle branch block, third degree heart block&#xD;
&#xD;
               -  Any factors that increase the risk of QTc prolongation or risk of arrhythmic&#xD;
                  events such as heart failure, hypokalaemia, congenital long QT syndrome, family&#xD;
                  history of long QT syndrome or unexplained sudden death under 40 years-of-age, or&#xD;
                  any concomitant medication known to prolong the QT interval&#xD;
&#xD;
               -  Ejection fraction &lt;55% or the lower limit of normal of the institutional&#xD;
                  standard.&#xD;
&#xD;
          -  History of pneumonitis within the last 5 years&#xD;
&#xD;
          -  History of severe hypersensitivity reactions to other mAbs&#xD;
&#xD;
          -  Immunosuppressive corticosteroid doses (&gt;10 mg prednisone daily or equivalent) within&#xD;
             4 weeks prior to the first dose of study treatment.&#xD;
&#xD;
          -  Active autoimmune disease or a documented history of autoimmune disease, except&#xD;
             vitiligo or resolved childhood asthma/atopy&#xD;
&#xD;
          -  Active infection requiring systemic treatment (antibacterial, antiviral, or antifungal&#xD;
             therapy) at start of treatment in this trial&#xD;
&#xD;
          -  Known history of human immunodeficiency virus infection or an active hepatitis B or C&#xD;
             virus infection&#xD;
&#xD;
          -  Interstitial lung disease&#xD;
&#xD;
          -  Chronic alcohol or drug abuse or any condition that, in the investigator's opinion,&#xD;
             makes him/her an unreliable trial patient or unlikely to complete the trial or unable&#xD;
             to comply with the protocol procedures&#xD;
&#xD;
          -  Women who are pregnant, nursing, or who plan to become pregnant in the trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Amsterdam UMC Locatie VUMC</name>
      <address>
        <city>Amsterdam</city>
        <zip>1081HV</zip>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Netherlands</country>
  </location_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>November 26, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 5, 2021</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</mesh_term>
    <mesh_term>Carcinoma, Non-Small-Cell Lung</mesh_term>
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:&#xD;
studies in products where Boehringer Ingelheim is not the license holder;&#xD;
studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;&#xD;
studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).&#xD;
For more details refer to: https://www.mystudywindow.com/msw/datasharing</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/NCT03780725
org study id: 1381-0003
secondary id: 2017-005046-30
nct id: NCT03780725
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The main objective of this study is to determine the biodistribution and intra-tumor
      accumulation of [89Zr]Zr-BI 754111 at baseline and its change upon treatment
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: The trial is divided in 2 Parts and will be conducted in a staggered approach, i.e. Part 2 follows Part 1. Part 2 will be initiated following a positive decision of the Study Monitoring Committee (SMC) after reviewing of all available data from Part 1 in order to assess whether a blockade of [89Zr]Zr-BI 754111 will be demonstrated.
primary purpose: Treatment
masking: None (Open Label)
measure: Standardized uptake values (SUVs) of [89Zr]Zr-BI 754111 for tumor uptake
time frame: Up to 29 days post-baseline
arm group label: Part 1: Ezabenlimab 240mg + BI 754111 600mg
arm group type: Experimental
arm group label: Part 2: Ezabenlimab 240mg + BI 754111 40mg
arm group type: Experimental
intervention type: Drug
intervention name: BI 754111
description: Solution for infusion
arm group label: Part 1: Ezabenlimab 240mg + BI 754111 600mg
arm group label: Part 2: Ezabenlimab 240mg + BI 754111 40mg
intervention type: Drug
intervention name: [89Zr]Zr-BI 754111
description: Solution for infusion
arm group label: Part 1: Ezabenlimab 240mg + BI 754111 600mg
arm group label: Part 2: Ezabenlimab 240mg + BI 754111 40mg
intervention type: Drug
intervention name: BI 754091
description: Solution for infusion
arm group label: Part 1: Ezabenlimab 240mg + BI 754111 600mg
arm group label: Part 2: Ezabenlimab 240mg + BI 754111 40mg
other name: Ezabenlimab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Netherlands
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Head and Neck Neoplasms
sharing ipd: No
ipd description: Clinical studies sponsored by Boehringer Ingelheim, phases I to IV, interventional and non-interventional, are in scope for sharing of the raw clinical study data and clinical study documents, except for the following exclusions:
studies in products where Boehringer Ingelheim is not the license holder;
studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials;
studies conducted in a single center or targeting rare diseases (because of limitations with anonymization).
For more details refer to: https://www.mystudywindow.com/msw/datasharing