<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/NCT04429087</url>
  </required_header>
  <id_info>
    <org_study_id>1438-0001</org_study_id>
    <secondary_id>2019-000729-31</secondary_id>
    <nct_id>NCT04429087</nct_id>
  </id_info>
  <brief_title>A Study to Test Different Doses of BI 764532 in Patients With Small Cell Lung Cancer and Other Neuroendocrine Tumours That Are Positive for DLL3</brief_title>
  <official_title>A First -in Human Phase I, Non-randomized, Open-label, Multi-center Dose Escalation Trial of BI 764532 Administered by Repeated Intravenous Infusions in Patients With Small Cell Lung Carcinoma and Other Neuroendocrine Neoplasms Expressing DLL3</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>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is open to adults with small cell lung cancer and other neuroendocrine cancers&#xD;
      that are positive for the tumour marker delta-like 3 (DLL3). The study is in people with&#xD;
      advanced cancer for whom previous treatment was not successful or no standard treatment&#xD;
      exists.&#xD;
&#xD;
      The purpose of this study is to find out the highest dose of BI 764532 and the best treatment&#xD;
      schedule that people can tolerate. BI 764532 is an antibody-like molecule (DLL3/CD3&#xD;
      bispecific) that may help the immune system fight cancer. In this study, BI 764532 is given&#xD;
      to people for the first time. That means no clinical data are available for BI 764532.&#xD;
&#xD;
      Participants get BI 764532 in regular intervals. If there is benefit for the participants and&#xD;
      if they can tolerate it, the treatment is given for a maximum of 3 years.&#xD;
&#xD;
      During this time, participants visit the study site about 20 times depending on the response&#xD;
      to the treatment. Doctors record any unwanted effects and regularly check the general health&#xD;
      of the participants.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2020</start_date>
  <completion_date type="Anticipated">September 2, 2024</completion_date>
  <primary_completion_date type="Anticipated">September 2, 2024</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)</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of patients with DLTs in the MTD evaluation period</measure>
    <time_frame>up to 36 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Maximum measured concentration (Cmax) of BI 764532</measure>
    <time_frame>up to 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the concentration-time curve (AUCτ) of the analyte over a uniform dosing interval τ</measure>
    <time_frame>up to 36 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response based on RECIST 1.1 criteria in patients with measurable disease</measure>
    <time_frame>up to 36 months</time_frame>
    <description>Objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients with measurable disease</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">193</enrollment>
  <condition>Patients With Small Cell Lung Carcinoma and Other Neoplasms</condition>
  <arm_group>
    <arm_group_label>BI 764532</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>BI 764532</intervention_name>
    <description>BI 764532</description>
    <arm_group_label>BI 764532</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Signed and dated, written informed consent form (ICF2) in accordance with&#xD;
             International Council for Harmonisation of Technical Requirements for Pharmaceuticals&#xD;
             for Human Use (ICH) - Good Clinical Practice (GCP) and local legislation prior to any&#xD;
             trial-specific procedures, sampling, or analyses.&#xD;
&#xD;
          -  Locally advanced or metastatic cancer not amenable to curative treatment; of following&#xD;
             histologies:&#xD;
&#xD;
               -  Small cell lung carcinoma (SCLC)&#xD;
&#xD;
               -  Large cells neuroendocrine lung carcinoma(LCNEC)&#xD;
&#xD;
               -  Neuroendocrine carcinoma (NEC) or small cell carcinoma of any other origin&#xD;
&#xD;
               -  Tumours must be positive for DLL3 expression (on archived tissue or instudy fresh&#xD;
                  biopsy) according to central pathology review in order to start BI 764532&#xD;
&#xD;
               -  Patients with tumours with mixed histologies for any above type are eligible only&#xD;
                  if neuroendocrine carcinoma/small tumor cells component is predominant and&#xD;
                  represent at least 50% of the overall tumour tissue.&#xD;
&#xD;
          -  For back-fill cohorts only: patient has agreed to and signed an IC to provide&#xD;
             mandatory pre-treatment and on-treatment fresh tumor biopsy.&#xD;
&#xD;
          -  Patient has failed or is not eligible for available standard therapies according to&#xD;
             local guidelines. Standard therapies should include at least one line of chemotherapy&#xD;
             that should include platinum for patients with small cells carcinoma tumors&#xD;
             histologies.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.&#xD;
&#xD;
          -  At least one evaluable lesion outside of CNS as defined per modified Response&#xD;
             Evaluation Criteria In Solid Tumors (RECIST) 1.1&#xD;
&#xD;
          -  Subjects with brain metastases are eligible provided they meet the following criteria:&#xD;
&#xD;
               -  Radiotherapy or surgery for brain metastases was completed at least 2 weeks prior&#xD;
                  to the first administration of BI 764532&#xD;
&#xD;
               -  Patient is off steroids for at least 7 days (physiologic doses of steroids are&#xD;
                  permitted), and the patient is off anti-epileptic drugs for at least 7 days or on&#xD;
                  stable doses of anti-epileptic drugs for malignant Central Nervous System (CNS)&#xD;
                  disease.&#xD;
&#xD;
          -  Adequate liver, bone marrow and renal organ function Futher inclusion criteria apply.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Previous treatment with T cell Engager (TcE) or cell therapies targeting Delta-Like&#xD;
             Ligand 3 (DLL3).&#xD;
&#xD;
          -  Anticoagulant treatment that cannot be safely interrupted based on opinion of the&#xD;
             investigator if medically needed (e.g. biopsy).&#xD;
&#xD;
          -  Persistent toxicity from previous treatments that has not resolved to = Common&#xD;
             Terminology Criteria for Adverse Events (CTCAE) Grade 1 (except for alopecia, CTCAE&#xD;
             Grade 2 neuropathy, asthenia/fatigue or grade 2 endocrinopathies controlled by&#xD;
             replacement therapy).&#xD;
&#xD;
          -  Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy&#xD;
             or any other form of immunosuppressive therapy within 7 days prior to the first dose&#xD;
             of BI 764532. Physiological replacement of steroids is allowed.&#xD;
&#xD;
          -  Prior anti-cancer therapy:&#xD;
&#xD;
               -  Patients who have been treated with any other anti-cancer drug within 3 weeks or&#xD;
                  within 5 half-life periods (whichever is shorter) prior to first administration&#xD;
                  of BI 764532.&#xD;
&#xD;
               -  Patients who have been treated with extensive field radiotherapy including whole&#xD;
                  brain irradiation within 2 weeks prior to first administration of BI 764532.&#xD;
&#xD;
          -  Other active malignancy that could interfere with the prognosis and treatment of the&#xD;
             disease of the study.&#xD;
&#xD;
          -  Major surgery within 28 days of first dose BI 764532.&#xD;
&#xD;
          -  Women who are pregnant, nursing/breast feeding or who plan to become pregnant or nurse&#xD;
             while in the trial or within 3 months after the last dose of study treatment.&#xD;
&#xD;
          -  Active infection that requires medical therapy or other clinically significant&#xD;
             intervention or within 2 weeks prior to study entry confirmed (PCR test or other&#xD;
             applicable test as per local requirments) or suspected SARS-CoV-2 infection or close&#xD;
             contact with an individual with confirmed SARS-CoV-2 infection. Further exclusion&#xD;
             criteria 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_contact>
    <last_name>Boehringer Ingelheim</last_name>
    <phone>1-800-243-0127</phone>
    <email>clintriage.rdg@boehringer-ingelheim.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Winship Cancer Institute</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>833-602-2368</phone>
      <email>unitedstates@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>833-602-2368</phone>
      <email>unitedstates@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>833-602-2368</phone>
      <email>unitedstates@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Carl Gustav Carus Dresden</name>
      <address>
        <city>Dresden</city>
        <zip>01307</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>08007234742</phone>
      <email>deutschland@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Köln (AöR)</name>
      <address>
        <city>Köln</city>
        <zip>50937</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>08007234742</phone>
      <email>deutschland@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Würzburg AÖR</name>
      <address>
        <city>Würzburg</city>
        <zip>97080</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>08007234742</phone>
      <email>deutschland@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East</name>
      <address>
        <city>Chiba, Kashiwa</city>
        <zip>277-8577</zip>
        <country>Japan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>0120201230</phone>
      <email>nippon@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar</name>
      <address>
        <city>Barcelona</city>
        <zip>08003</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>900876092</phone>
      <email>espana@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>900876092</phone>
      <email>espana@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de Navarra</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>900876092</phone>
      <email>espana@bitrialsupport.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Clínico de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46010</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Boehringer Ingelheim</last_name>
      <phone>900876092</phone>
      <email>espana@bitrialsupport.com</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Japan</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mystudywindow.com</url>
    <description>Related Info</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>June 10, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 12, 2020</study_first_posted>
  <last_update_submitted>August 18, 2023</last_update_submitted>
  <last_update_submitted_qc>August 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 22, 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>Carcinoma</mesh_term>
    <mesh_term>Neoplasms</mesh_term>
    <mesh_term>Lung Neoplasms</mesh_term>
    <mesh_term>Small Cell Lung Carcinoma</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: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. 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</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/NCT04429087
org study id: 1438-0001
secondary id: 2019-000729-31
nct id: NCT04429087
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is open to adults with small cell lung cancer and other neuroendocrine cancers
      that are positive for the tumour marker delta-like 3 (DLL3). The study is in people with
      advanced cancer for whom previous treatment was not successful or no standard treatment
      exists.

      The purpose of this study is to find out the highest dose of BI 764532 and the best treatment
      schedule that people can tolerate. BI 764532 is an antibody-like molecule (DLL3/CD3
      bispecific) that may help the immune system fight cancer. In this study, BI 764532 is given
      to people for the first time. That means no clinical data are available for BI 764532.

      Participants get BI 764532 in regular intervals. If there is benefit for the participants and
      if they can tolerate it, the treatment is given for a maximum of 3 years.

      During this time, participants visit the study site about 20 times depending on the response
      to the treatment. Doctors record any unwanted effects and regularly check the general health
      of the participants.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose (MTD)
time frame: up to 36 months
description: Maximum tolerated dose (MTD) in any studied regimen defined as the highest dose with less than 25% risk of the true Dose Limiting Toxicity (DLT) rate being equal or above 33% during the MTD evaluation period. Separate MTDs will be determined for each Regimen.
measure: Number of patients with DLTs in the MTD evaluation period
time frame: up to 36 months
measure: Maximum measured concentration (Cmax) of BI 764532
time frame: up to 36 months
measure: Area under the concentration-time curve (AUCτ) of the analyte over a uniform dosing interval τ
time frame: up to 36 months
measure: Objective response based on RECIST 1.1 criteria in patients with measurable disease
time frame: up to 36 months
description: Objective response based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in patients with measurable disease
arm group label: BI 764532
arm group type: Experimental
intervention type: Drug
intervention name: BI 764532
description: BI 764532
arm group label: BI 764532
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Boehringer Ingelheim
phone: 1-800-243-0127
email: clintriage.rdg@boehringer-ingelheim.com
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Germany
country: Japan
country: Spain
country: United States
url: https://www.mystudywindow.com
description: Related Info
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Neoplasms
mesh term: Lung Neoplasms
mesh term: Small Cell Lung Carcinoma
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: 1. studies in products where Boehringer Ingelheim is not the license holder; 2. studies regarding pharmaceutical formulations and associated analytical methods, and studies pertinent to pharmacokinetics using human biomaterials; 3. 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