<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/NCT03840902</url>
  </required_header>
  <id_info>
    <org_study_id>MS200647_0005</org_study_id>
    <secondary_id>2018-003265-34</secondary_id>
    <nct_id>NCT03840902</nct_id>
  </id_info>
  <brief_title>M7824 With cCRT in Unresectable Stage III Non-small Cell Lung Cancer (NSCLC)</brief_title>
  <official_title>A Multicenter, Double Blind, Randomized, Controlled Study of M7824 With Concurrent Chemoradiation Followed by M7824 Versus Concurrent Chemoradiation Plus Placebo Followed by Durvalumab in Participants With Unresectable Stage III Non-small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>EMD Serono Research &amp; Development Institute, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck KGaA, Darmstadt, Germany</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>EMD Serono</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The main purpose of this study is to evaluate safety and efficacy in participants treated&#xD;
      with concomitant chemoradiation therapy (cCRT) plus M7824 followed by M7824 compared to cCRT&#xD;
      plus placebo followed by durvalumab.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Based on recommendations by an external IDMC, Sponsor decided to discontinue this clinical&#xD;
    study due to a low likelihood of achieving superiority in the efficacy endpoints versus&#xD;
    standard of care.&#xD;
  </why_stopped>
  <start_date type="Actual">April 16, 2019</start_date>
  <completion_date type="Actual">February 17, 2023</completion_date>
  <primary_completion_date type="Actual">February 17, 2023</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Investigator</measure>
    <time_frame>Time from randomization to final assessment at 3 years and 6 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Occurrence of Treatment Emergent Adverse Events (TEAEs) and Treatment-related AEs</measure>
    <time_frame>Time from randomization to final assessment at 3 years and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>Time from randomization to final assessment at 3 years and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)</measure>
    <time_frame>Time from randomization to final assessment at 3 years and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response Assessed by Investigator</measure>
    <time_frame>Time from randomization to final assessment at 3 years and 6 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pharmacokinetics Profile of M7824 in Terms of Concentration Immediately at End of Infusion (Ceoi) and Concentration Immediately Before Next Dosing (Ctrough)</measure>
    <time_frame>Time from randomization to final assessment at 17 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity of M7824 as Measured by Antidrug Antibody (ADA) Assays</measure>
    <time_frame>Time from randomization to final assessment at 17 months</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">168</enrollment>
  <condition>Non-small Cell Lung Cancer</condition>
  <arm_group>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will receive cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants will receive cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with placebo matched to M7824 followed by durvalumab.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>M7824</intervention_name>
    <description>Participants will receive intravenous infusion of 1200 milligram (mg) M7824 over 1 hour every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Participants will receive intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.</description>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Durvalumab</intervention_name>
    <description>Participants will receive intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) over 1 hour q2w up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.</description>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Etoposide</intervention_name>
    <description>Participants will receive etoposide 50 mg/m^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT.</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <description>Participants will receive pemetrexed at a dose of 500 mg/m^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT.</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <description>Participants will receive carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Paclitaxel</intervention_name>
    <description>Participants will receive paclitaxel intravenously at a dose of 45 mg/m^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cisplatin</intervention_name>
    <description>In combination with etoposide, participants will receive cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants will receive cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>Intensity Modulated Radiation Therapy (IMRT)</intervention_name>
    <description>Participants will receive IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).</description>
    <arm_group_label>Arm 1: cCRT plus M7824 followed by M7824</arm_group_label>
    <arm_group_label>Arm 2: cCRT plus placebo followed by durvalumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must have histologically documented NSCLC who present with Stage III&#xD;
             locally advanced, unresectable disease (International Association for the Study of&#xD;
             Lung Cancer Staging Manual in Thoracic Oncology&#xD;
&#xD;
          -  Participants with tumor harboring an Epidermal growth factor receptor (EGFR)&#xD;
             sensitizing (activating) mutation, Anaplastic lymphoma kinase (ALK) translocation,&#xD;
             ROS-1 rearrangement are eligible.&#xD;
&#xD;
          -  Participants must have adequate pulmonary function defined as a forced expiratory&#xD;
             volume in 1 second (FEV1) greater than equals to (&gt;=) 1.2 liters or &gt;= 50% of&#xD;
             predicted normal volume measured within 3 weeks prior to randomization.&#xD;
&#xD;
          -  Adequate hematological, hepatic and renal function as defined in the protocol&#xD;
&#xD;
          -  Contraceptive use by males or females will be consistent with local regulations on&#xD;
             contraception methods for those participating in clinical studies&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with Mixed small cell with non-small cell lung cancer histology&#xD;
&#xD;
          -  Recent major surgery within 4 weeks prior to entry into the study&#xD;
&#xD;
          -  Significant acute or chronic infections including human immunodeficiency virus (HIV)&#xD;
             or known acquired immunodeficiency syndrome, Active hepatitis B virus (HBV) or&#xD;
             hepatitis C virus (HCV) infection and active tuberculosis&#xD;
&#xD;
          -  Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness&#xD;
             requiring hospitalization&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic treatment in past 1 year (i.e.,&#xD;
             with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)&#xD;
&#xD;
          -  Any prior systemic cytotoxic chemotherapy for their NSCLC or any antibody or drug&#xD;
             targeting T-cell coregulatory proteins&#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>Medical Responsible</last_name>
    <role>Study Director</role>
    <affiliation>Merck KGaA, Darmstadt, Germany</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California Irvine Medical Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCLA Hematology Oncology - Main Site - 2020 Santa Monica</name>
      <address>
        <city>Santa Monica</city>
        <state>California</state>
        <zip>90404</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Health - Memorial Hospital - Memorial Hospital</name>
      <address>
        <city>Colorado Springs</city>
        <state>Colorado</state>
        <zip>80909</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology Oncology Associates</name>
      <address>
        <city>Fort Collins</city>
        <state>Colorado</state>
        <zip>80528</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Lynn Cancer Institute Center</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Holy Cross Hospital - Michael and Dianne Bienes CCC</name>
      <address>
        <city>Fort Lauderdale</city>
        <state>Florida</state>
        <zip>33308</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sylvester Comprehensive Cancer Center - University of Miami Health System</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Chicago Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>American Health Network of Indiana, LLC</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Franciscan St. Francis Health Cancer Center</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46237</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baptist Health Lexington Oncology Associates</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland - DUPLICATE/Pediatric Surgery</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Health System</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55902</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Columbia University Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology Oncology Center of Nyack Hospital</name>
      <address>
        <city>Nyack</city>
        <state>New York</state>
        <zip>10960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FirstHealth of the Carolinas, Inc.</name>
      <address>
        <city>Pinehurst</city>
        <state>North Carolina</state>
        <zip>28374</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The James Cancer Hospital and Solove Research Institute</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt University Medical Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas MD Anderson Cancer Center - Unit 432 Thoracic Head and Neck Medical Oncology</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sanatorio Allende</name>
      <address>
        <city>Cordoba</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro Polivalente de Asistencia e Inv. Clinica CER</name>
      <address>
        <city>San Juan</city>
        <country>Argentina</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bendigo Hospital</name>
      <address>
        <city>Bendigo</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Townsville Hospital</name>
      <address>
        <city>Douglas</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Calvary Central Districts Hospital</name>
      <address>
        <city>Elizabeth Vale</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St Vincent's Hospital Melbourne - PARENT</name>
      <address>
        <city>Fitzroy</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Geelong - PARENT</name>
      <address>
        <city>Geelong</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Heidelberg Heights</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centro de Investigacion Pergamino SA</name>
      <address>
        <city>Pergamino</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Prince of Wales Hospital</name>
      <address>
        <city>Randwick</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunshine Hospital</name>
      <address>
        <city>St Albans</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royal North Shore Hospital</name>
      <address>
        <city>St Leonards</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South West Healthcare - South West Oncology</name>
      <address>
        <city>Warrnambool</city>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UZ Leuven</name>
      <address>
        <city>Leuven</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinique et Maternite St Elisabeth Namur</name>
      <address>
        <city>Namur</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>AZ Delta</name>
      <address>
        <city>Roeselare</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Mont-Godinne</name>
      <address>
        <city>Yvoir</city>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital de Câncer de Barretos - Fundação Pio XII</name>
      <address>
        <city>Barretos</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clínica de Neoplasias Litoral Ltda.</name>
      <address>
        <city>Itajaí</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>HGB - Hospital Giovanni Battista - Mãe de Deus Center - Centro de Pesquisa Clínica - Instituto do Câncer</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital São Lucas da PUCRS</name>
      <address>
        <city>Porto Alegre</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>COI - Clínicas Oncológicas Integradas</name>
      <address>
        <city>Rio de Janeiro</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>A. C. Camargo Cancer Center - Fundação Antônio Prudente</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira</name>
      <address>
        <city>São Paulo</city>
        <country>Brazil</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>BC Cancer Agency Center for the Southern Interior</name>
      <address>
        <city>Kelowna</city>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peking University Cancer Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jilin Cancer Hospital - Oncology</name>
      <address>
        <city>Changchun</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hangzhou First People's Hospital</name>
      <address>
        <city>Hangzhou</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fakultni nemocnice Olomouc - Dept of Onkologicka klinika</name>
      <address>
        <city>Olomouc</city>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier de la Côte Basque - Service de Pneumologie</name>
      <address>
        <city>Bayonne</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Nord - AP-HM Marseille# - Service d'Oncologie Multidisciplinaire</name>
      <address>
        <city>Marseille cedex 20</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Curie - Centre de Lutte Contre le Cancer (CLCC) de Paris - Service d'Oncologie Médicale</name>
      <address>
        <city>Paris Cedex 05</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU Nantes - Hôpital Guillaume et René Laënnec - Service de Pneumologie</name>
      <address>
        <city>Saint Herblain</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asklepios Klinik Harburg - Medizinische Abteilung I</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Pius-Hospital Oldenburg - Klinik f. Haematologie und Onkologie</name>
      <address>
        <city>Oldenburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nippon Medical School Hospital - Dept of Respiratory Medicine</name>
      <address>
        <city>Bunkyo-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital - Dept of Respiratory Medicine</name>
      <address>
        <city>Bunkyo-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Medical University International Medical Center - Dept of Respiratory Medicine</name>
      <address>
        <city>Hidaka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Cancer Center Hospital East - Dept of Respiratory Medicine</name>
      <address>
        <city>Kashiwa-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kobe City Hospital Organization Kobe City Medical Center General Hospital - Dept of Respiratory Medicine</name>
      <address>
        <city>Kobe-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cancer Institute Hospital of JFCR - Dept of Respiratory Medicine</name>
      <address>
        <city>Koto-ku</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kurume University Hospital - Dept of Lung Cancer Center</name>
      <address>
        <city>Kurume-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aichi Cancer Center Hospital - Dept of Respiratory Medicine</name>
      <address>
        <city>Nagoya-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka Medical Center for Cancer and Cardiovascular Diseases</name>
      <address>
        <city>Osaka-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kindai University Hospital (13859)</name>
      <address>
        <city>Osakasayama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shizuoka Cancer Center</name>
      <address>
        <city>Sunto-gun</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kanagawa Cancer Center - Dept of Respiratory Medicine</name>
      <address>
        <city>Yokohama-shi</city>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keimyung University Dongsan Hospital</name>
      <address>
        <city>Daegu</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Severance Hospital, Yonsei University</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Catholic University of Korea, Seoul St. Mary's Hospital</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jeroen Bosch Ziekenhuis</name>
      <address>
        <city>'s Hertogenbosch</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Meander Medisch Centrum - Dep of Pulmonology</name>
      <address>
        <city>Amersfoort</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Amphia Ziekenhuis - PARENT - Parent</name>
      <address>
        <city>Breda</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Martini ziekenhuis</name>
      <address>
        <city>Groningen</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuis St. Jansdal</name>
      <address>
        <city>Harderwijk</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Antonius Ziekenhuis - Dept Pulmonology - Nieuwegein</name>
      <address>
        <city>Nieuwegein</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Elisabeth Ziekenhuis - Parent</name>
      <address>
        <city>Tilburg</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ISALA Klinieken Locatie Sophia</name>
      <address>
        <city>Zwolle</city>
        <country>Netherlands</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital del Mar - Servicio de Oncologia</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron - Dept of Oncology</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia</name>
      <address>
        <city>L'Hospitalet de Llobregat</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universidad de Navarra (MAD) - Oncology Service</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario 12 de Octubre - Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Clinico San Carlos - Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Puerta de Hierro Majadahonda</name>
      <address>
        <city>Majadahonda</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Regional Universitario de Malaga</name>
      <address>
        <city>Málaga</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Universidad de Navarra</name>
      <address>
        <city>Pamplona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Complejo Hospitalario Universitario de Santiago - Servicio de Oncologia Medica</name>
      <address>
        <city>Santiago de Compostela</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Nuestra Señora de Valme - Servicio de Oncologia</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio - Servicio de Oncologia</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen Macarena - Servicio de Oncologia</name>
      <address>
        <city>Sevilla</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica</name>
      <address>
        <city>Valencia</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Alvaro Cunqueiro - Servicio de Oncologia</name>
      <address>
        <city>Vigo</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Taichung Veterans General Hospital</name>
      <address>
        <city>Taichung</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chi Mei Medical Center, Liou Ying</name>
      <address>
        <city>Tainan</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tri-Service General Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Argentina</country>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Brazil</country>
    <country>Canada</country>
    <country>China</country>
    <country>Czechia</country>
    <country>France</country>
    <country>Germany</country>
    <country>Japan</country>
    <country>Korea, Republic of</country>
    <country>Netherlands</country>
    <country>Spain</country>
    <country>Taiwan</country>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200647_0005</url>
    <description>Trial Awareness and Transparency website</description>
  </link>
  <link>
    <url>https://medical.emdserono.com/en_US/home.html</url>
    <description>US Medical Information website, Medical Resources</description>
  </link>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>February 12, 2019</study_first_submitted>
  <study_first_submitted_qc>February 12, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>March 2, 2023</last_update_submitted>
  <last_update_submitted_qc>March 2, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Non-small Cell Lung Cancer</keyword>
  <keyword>Bintrafusp alfa (proposed INN)</keyword>
  <keyword>M7824</keyword>
  <keyword>Durvalumab</keyword>
  <keyword>Stage III</keyword>
  <keyword>INTR@PID LUNG 005</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
    <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>Paclitaxel</mesh_term>
    <mesh_term>Etoposide</mesh_term>
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
    <mesh_term>Durvalumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_info_type>Statistical Analysis Plan (SAP)</ipd_info_type>
    <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
    <ipd_time_frame>Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union</ipd_time_frame>
    <ipd_access_criteria>Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.</ipd_access_criteria>
    <ipd_url>http://bit.ly/IPD21</ipd_url>
  </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/NCT03840902
org study id: MS200647_0005
secondary id: 2018-003265-34
nct id: NCT03840902
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The main purpose of this study is to evaluate safety and efficacy in participants treated
      with concomitant chemoradiation therapy (cCRT) plus M7824 followed by M7824 compared to cCRT
      plus placebo followed by durvalumab.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed by Investigator
time frame: Time from randomization to final assessment at 3 years and 6 months
measure: Occurrence of Treatment Emergent Adverse Events (TEAEs) and Treatment-related AEs
time frame: Time from randomization to final assessment at 3 years and 6 months
measure: Overall Survival
time frame: Time from randomization to final assessment at 3 years and 6 months
measure: Objective response according to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
time frame: Time from randomization to final assessment at 3 years and 6 months
measure: Duration of Response Assessed by Investigator
time frame: Time from randomization to final assessment at 3 years and 6 months
measure: Pharmacokinetics Profile of M7824 in Terms of Concentration Immediately at End of Infusion (Ceoi) and Concentration Immediately Before Next Dosing (Ctrough)
time frame: Time from randomization to final assessment at 17 months
measure: Immunogenicity of M7824 as Measured by Antidrug Antibody (ADA) Assays
time frame: Time from randomization to final assessment at 17 months
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group type: Experimental
description: Participants will receive cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with M7824 followed by M7824.
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
arm group type: Active Comparator
description: Participants will receive cCRT: Cisplatin/Etoposide or Carboplatin/Paclitaxel or Cisplatin/Pemetrexed concomitant with Intensity Modulated Radiation Therapy (IMRT) along with placebo matched to M7824 followed by durvalumab.
intervention type: Drug
intervention name: M7824
description: Participants will receive intravenous infusion of 1200 milligram (mg) M7824 over 1 hour every 2 weeks (q2w) during cCRT and up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
arm group label: Arm 1: cCRT plus M7824 followed by M7824
intervention type: Drug
intervention name: Placebo
description: Participants will receive intravenous infusion of placebo matched to M7824 over 1 hour q2w during cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Drug
intervention name: Durvalumab
description: Participants will receive intravenous infusion of durvalumab 10 milligram per kilogram (mg/Kg) over 1 hour q2w up to 1 year after cCRT until unacceptable toxicity, confirmed disease progression assessed by investigator.
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Drug
intervention name: Etoposide
description: Participants will receive etoposide 50 mg/m^2 intravenously over a minimum of 30 minutes up to 60 minutes daily on Day 1 to 5 and Day 29 to 33 during cCRT.
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Drug
intervention name: Pemetrexed
description: Participants will receive pemetrexed at a dose of 500 mg/m^2 intravenously over 10 minutes or according to local standards on Days 1, 22, and 43 during cCRT.
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Drug
intervention name: Carboplatin
description: Participants will receive carboplatin intravenously based on area under curve (AUC) 2 over 30 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Drug
intervention name: Paclitaxel
description: Participants will receive paclitaxel intravenously at a dose of 45 mg/m^2 over 60 minutes on Day 1, Day 8, Day 15, Day 22, Day 29, Day 36, and Day 43 during cCRT.
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Drug
intervention name: Cisplatin
description: In combination with etoposide, participants will receive cisplatin 50 mg/m^2 intravenously over 60 minutes on Days 1, 8, 29, and 36 during cCRT. In combination with pemetrexed, participants will receive cisplatin 75 mg/m2 intravenously over 60 minutes on Days 1, 22, and 43 during cCRT.
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
intervention type: Radiation
intervention name: Intensity Modulated Radiation Therapy (IMRT)
description: Participants will receive IMRT 5 fractions per week for about 6 weeks (Total 60 gray [Gy]).
arm group label: Arm 1: cCRT plus M7824 followed by M7824
arm group label: Arm 2: cCRT plus placebo followed by durvalumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Responsible
role: Study Director
affiliation: Merck KGaA, Darmstadt, Germany
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country: Argentina
country: Australia
country: Belgium
country: Brazil
country: Canada
country: China
country: Czechia
country: France
country: Germany
country: Japan
country: Korea, Republic of
country: Netherlands
country: Spain
country: Taiwan
country: United States
url: https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200647_0005
description: Trial Awareness and Transparency website
url: https://medical.emdserono.com/en_US/home.html
description: US Medical Information website, Medical Resources
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carcinoma, Non-Small-Cell Lung
mesh term: Paclitaxel
mesh term: Etoposide
mesh term: Carboplatin
mesh term: Pemetrexed
mesh term: Durvalumab
sharing ipd: Yes
ipd description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
ipd info type: Study Protocol
ipd info type: Statistical Analysis Plan (SAP)
ipd info type: Clinical Study Report (CSR)
ipd time frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
ipd access criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
ipd url: http://bit.ly/IPD21