<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/NCT02259582</url>
  </required_header>
  <id_info>
    <org_study_id>M18-007</org_study_id>
    <nct_id>NCT02259582</nct_id>
  </id_info>
  <brief_title>A Study of Carboplatin, Pemetrexed Plus Placebo vs Carboplatin, Pemetrexed Plus 1 or 2 Truncated Courses of Demcizumab in Subjects With Non-Squamous Non-Small Cell Lung Cancer</brief_title>
  <acronym>DENALI</acronym>
  <official_title>A 2-Arm Phase 2 Double-Blind Randomized Study of Carboplatin, Pemetrexed Plus Placebo Versus Carboplatin, Pemetrexed Plus Truncated Demcizumab as First-Line Treatment in Subjects With Stage IV Non-Squamous Non-Small Cell Lung Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>OncoMed Pharmaceuticals, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Celgene Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Mereo BioPharma</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      A randomized, double-blind, 3-arm (1:1:1) study in subjects with first-line Stage IV&#xD;
      non-squamous NSCLC. The purpose is to test the efficacy and safety of demcizumab, when given&#xD;
      in combination with carboplatin and pemetrexed compared to placebo. The administration of&#xD;
      carboplatin and pemetrexed is a standard treatment for patients with non-squamous non-small&#xD;
      cell lung cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will be enrolled at centers in North America, Western Europe, Australia and New&#xD;
      Zealand. Up to 28 days (4 weeks) prior to treatment.&#xD;
&#xD;
      If enrolled in the study, you will receive intravenous (in the vein) infusions of demcizumab&#xD;
      (or placebo), carboplatin, and pemetrexed administered on the same day, every 21 days for 4&#xD;
      cycles, or until it has been shown that your cancer has gotten worse. If your physician&#xD;
      decides to delay treatment with one of the agents due to side effects, the other agents may&#xD;
      still be administered as scheduled. After 4 cycles, if you have stable or improved disease,&#xD;
      you will continue to receive pemetrexed once every 21 days as maintenance therapy. After 8&#xD;
      cycles, if you have stable or improved disease, you may receive demcizumab (or placebo),&#xD;
      every 21 days for 4 more cycles.&#xD;
&#xD;
      You will undergo assessments every 6 weeks to determine the status of your disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 2015</start_date>
  <completion_date type="Actual">April 7, 2017</completion_date>
  <primary_completion_date type="Actual">April 7, 2017</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>To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.</measure>
    <time_frame>Response assessment data was collected until the subject started alternative anti-cancer treatment or developed progressive disease, whichever occurred first, assessed up to approximately 26 months.</time_frame>
    <description>Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">82</enrollment>
  <condition>Nonsquamous Nonsmall Cell Neoplasm of Lung</condition>
  <arm_group>
    <arm_group_label>Arm 1 Pem, carbo, placebo x 4 cycles</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Pemetrexed (500 mg/m2),carboplatin (area under the concentration-time curve of 6 mg/mL x min) once every 21 days X 4 cycles, pemetrexed maintenance and placebo starting at Day 84</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 Pem, carbo x 4 cycles, one course of dem</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, one course of demcizumab 5mg/kg, maintenance pemetrexed + placebo starting on Day 84</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 3 pem, carbo, dem x 4 cycles, dem retreatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, maintenance pemetrexed starting on Day 84. 2 courses of demcizumab 5 mg/kg</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pemetrexed</intervention_name>
    <arm_group_label>Arm 1 Pem, carbo, placebo x 4 cycles</arm_group_label>
    <arm_group_label>Arm 2 Pem, carbo x 4 cycles, one course of dem</arm_group_label>
    <arm_group_label>Arm 3 pem, carbo, dem x 4 cycles, dem retreatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Carboplatin</intervention_name>
    <arm_group_label>Arm 1 Pem, carbo, placebo x 4 cycles</arm_group_label>
    <arm_group_label>Arm 2 Pem, carbo x 4 cycles, one course of dem</arm_group_label>
    <arm_group_label>Arm 3 pem, carbo, dem x 4 cycles, dem retreatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>demcizumab</intervention_name>
    <arm_group_label>Arm 2 Pem, carbo x 4 cycles, one course of dem</arm_group_label>
    <arm_group_label>Arm 3 pem, carbo, dem x 4 cycles, dem retreatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          1. Signed Informed Consent Form&#xD;
&#xD;
          2. Histologically or cytologically confirmed Stage IV non-squamous NSCLC&#xD;
&#xD;
          3. Availability of FFPE (formalin-fixed paraffin-embedded) tumor tissue, either fresh&#xD;
             core-needle-biopsied or archived&#xD;
&#xD;
          4. Age &gt; or = to 21 years&#xD;
&#xD;
          5. ECOG (Eastern Cooperative Oncology Group) performance status of 0 or 1&#xD;
&#xD;
          6. Disease that is measurable per RECIST v1.1&#xD;
&#xD;
          7. Adequate organ and marrow function&#xD;
&#xD;
          8. For women of childbearing potential, agreement to use two effective forms of&#xD;
             contraception&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically documented, advanced, mixed non-small cell and small&#xD;
             cell tumors or mixed adenosquamous carcinomas&#xD;
&#xD;
          2. NSCLC with known EGFR (epidermal growth factor receptor ) mutation or anaplastic&#xD;
             lymphoma kinase (ALK) gene translocation (such as EML4 [echinoderm&#xD;
             microtubule-associated protein-like 4]-ALK [anaplastic lymphoma kinase])&#xD;
&#xD;
          3. Prior or ongoing therapy (including chemotherapy, antibody therapy, tyrosine kinase&#xD;
             inhibitors, radiotherapy, immunotherapy, hormonal therapy, or investigational therapy)&#xD;
             for the treatment of Stage IV non-squamous NSCLC&#xD;
&#xD;
          4. Evidence of tumor invading major blood vessels, cavitation of one or more pulmonary&#xD;
             tumor mass(es) or tracheo-esophageal fistula&#xD;
&#xD;
          5. Brain metastases, leptomeningeal disease, uncontrolled seizure disorder, or active&#xD;
             neurologic disease&#xD;
&#xD;
          6. Malignancies other than non-squamous NSCLC successfully treated within 3 years prior&#xD;
             to randomization (with the exception of certain early-stage cancers)&#xD;
&#xD;
          7. History of a significant allergic reaction attributed to humanized or human monoclonal&#xD;
             antibody therapy&#xD;
&#xD;
          8. Significant intercurrent illness defined as an illness that may result in the&#xD;
             subject's death prior to their death from non-squamous NSCLC and/or significantly&#xD;
             limit their ability to comply with the requirements of this study&#xD;
&#xD;
          9. Recent hemoptysis &gt;2.5 mL or serious bleeding from another site, known bleeding&#xD;
             disorder or coagulopathy or therapeutic anti-coagulation&#xD;
&#xD;
         10. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days&#xD;
             prior to randomization, or anticipation of need for major surgical procedure during&#xD;
             the course of the study&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Desert Hematology Oncology Medical Group, Inc.</name>
      <address>
        <city>Rancho Mirage</city>
        <state>California</state>
        <zip>92270</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>. 94143-1705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital at Yale-New Haven</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510-3221</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ocala Oncology Center</name>
      <address>
        <city>Ocala</city>
        <state>Florida</state>
        <zip>34471</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edward H. Kaplan MD &amp; Associates</name>
      <address>
        <city>Skokie</city>
        <state>Illinois</state>
        <zip>60076</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Anne Arundel Medical Center</name>
      <address>
        <city>Annapolis</city>
        <state>Maryland</state>
        <zip>21401</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>Karmanos Cancer Institute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>4820I</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Broome Oncology, LLC</name>
      <address>
        <city>Binghamton</city>
        <state>New York</state>
        <zip>13905</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology Oncology Associates of Rockland</name>
      <address>
        <city>Nyack</city>
        <state>New York</state>
        <zip>10960</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gaston Hematology &amp; Oncology</name>
      <address>
        <city>Gastonia</city>
        <state>North Carolina</state>
        <zip>28054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Gabrail Cancer Center Research</name>
      <address>
        <city>Canton</city>
        <state>Ohio</state>
        <zip>44718</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospitals of Cleveland</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Baylor Charles A. Sammons Cancer Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75246</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Texas Medical Branch at Galveston</name>
      <address>
        <city>Galveston</city>
        <state>Texas</state>
        <zip>77555</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Texas Oncology-Sherman</name>
      <address>
        <city>Sherman</city>
        <state>Texas</state>
        <zip>75090-0504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Compass Oncology</name>
      <address>
        <city>Vancouver</city>
        <state>Washington</state>
        <zip>98684</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chris O'Brien Lifehouse</name>
      <address>
        <city>Camperdown</city>
        <state>New South Wales</state>
        <zip>2050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Kinghorn Cancer Centre</name>
      <address>
        <city>Darlinghurst</city>
        <state>New South Wales</state>
        <zip>2010</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Coast Cancer Institute Port Macquarie Base Hospital</name>
      <address>
        <city>Port Macquarie</city>
        <state>New South Wales</state>
        <zip>2444</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Royall Brisbane &amp; Women's Hospital</name>
      <address>
        <city>Herston</city>
        <state>Queensland</state>
        <zip>4029</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Icon Cancer Foundation</name>
      <address>
        <city>Milton</city>
        <state>Queensland</state>
        <zip>4064</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Queen Elizabeth Hospital</name>
      <address>
        <city>Woodville South</city>
        <state>South Australia</state>
        <zip>5011</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Monash Health, Monash Cancer Centre-Moorabbin</name>
      <address>
        <city>Bentleigh East</city>
        <state>Victoria</state>
        <zip>3165</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. John of God Subiaco Hospital</name>
      <address>
        <city>Subiaco</city>
        <state>Western Australia</state>
        <zip>6008</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ziekenhuisnetwerk Antwerpen- Koningin Paola Kinderzickenhuis</name>
      <address>
        <city>Antwerpen</city>
        <zip>2020</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Hopital de Charleroi- Site Notre-Dame</name>
      <address>
        <city>Charleroi</city>
        <zip>6000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre Hospitalier Jolimont-Lobbes</name>
      <address>
        <city>La Louviere</city>
        <zip>7100</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHR de Ia Citadelle</name>
      <address>
        <city>Liege</city>
        <zip>4000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Istituti Ospitalieri</name>
      <address>
        <city>Cremona</city>
        <state>Lombardia</state>
        <zip>26100</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliera Città della Salute e della Scienza di Torino</name>
      <address>
        <city>Torino</city>
        <state>Piemonte</state>
        <zip>10126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Smilow Cancer Hospital at Yale-New Haven</name>
      <address>
        <city>Aviano</city>
        <state>Pordenone</state>
        <zip>33081</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Azienda Ospedaliero Universitaria Pisana</name>
      <address>
        <city>Pisa</city>
        <state>Toscana</state>
        <zip>56126</zip>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Badalona</city>
        <state>Barcelona</state>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Puerta de Hierro Majadahonda</name>
      <address>
        <city>Majadahonda</city>
        <state>Madrid</state>
        <zip>28222</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Nuestra Senora de Sonsoles</name>
      <address>
        <city>Avila</city>
        <zip>05004</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall D'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic de Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institute Catalan de Oncologia (ICO L'Hospitalet)</name>
      <address>
        <city>Barcelona</city>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Germans Trias i Pujol</name>
      <address>
        <city>Barcelona</city>
        <zip>08916</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario Gregorio Marañon</name>
      <address>
        <city>Madrid</city>
        <zip>28009</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Clinico San Carlos</name>
      <address>
        <city>Madrid</city>
        <zip>28040</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Madrid Universitario Sanchinarro</name>
      <address>
        <city>Madrid</city>
        <zip>28050</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Belgium</country>
    <country>Italy</country>
    <country>Spain</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2020</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>October 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 8, 2014</study_first_posted>
  <results_first_submitted>May 21, 2018</results_first_submitted>
  <results_first_submitted_qc>August 14, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 20, 2018</results_first_posted>
  <last_update_submitted>September 7, 2020</last_update_submitted>
  <last_update_submitted_qc>September 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Phase 2</keyword>
  <keyword>histologically</keyword>
  <keyword>confirmed</keyword>
  <keyword>malignancy</keyword>
  <keyword>metastatic</keyword>
  <keyword>pemetrexed</keyword>
  <keyword>carboplatin</keyword>
  <keyword>carcinoma</keyword>
  <keyword>non small cell lung</keyword>
  <keyword>lung neoplasms</keyword>
  <keyword>lung diseases</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carboplatin</mesh_term>
    <mesh_term>Pemetrexed</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>April 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT02259582/SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 29, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/82/NCT02259582/Prot_ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo/Placebo Arm (Arm 1)</title>
          <description>Placebo plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="P2">
          <title>Demcizumab/Placebo Arm (Arm 2)</title>
          <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="P3">
          <title>Demcizumab/Demcizumab Arm (Arm 3)</title>
          <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), demcizumab plus pemetrexed (4 cycles)</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="25"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="17"/>
                <participants group_id="P3" count="21"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Disease progression</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="15"/>
                <participants group_id="P3" count="17"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Subject Adherence to Protocol</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo/Placebo Arm (Arm 1)</title>
          <description>Placebo plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="B2">
          <title>Demcizumab/Placebo Arm (Arm 2)</title>
          <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="B3">
          <title>Demcizumab/Demcizumab Arm (Arm 3)</title>
          <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), demcizumab plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="25"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="29"/>
            <count group_id="B4" value="82"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60" lower_limit="40" upper_limit="77"/>
                    <measurement group_id="B2" value="66" lower_limit="31" upper_limit="76"/>
                    <measurement group_id="B3" value="61" lower_limit="39" upper_limit="76"/>
                    <measurement group_id="B4" value="62" lower_limit="31" upper_limit="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="12"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="17"/>
                    <measurement group_id="B4" value="40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="28"/>
                    <measurement group_id="B4" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>Belgium</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="7"/>
                    <measurement group_id="B4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Italy</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Australia</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="10"/>
                    <measurement group_id="B4" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Spain</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.</title>
        <description>Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.</description>
        <time_frame>Response assessment data was collected until the subject started alternative anti-cancer treatment or developed progressive disease, whichever occurred first, assessed up to approximately 26 months.</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo/Placebo Arm (Arm 1)</title>
            <description>Placebo plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
          </group>
          <group group_id="O2">
            <title>Demcizumab/Placebo Arm (Arm 2)</title>
            <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
          </group>
          <group group_id="O3">
            <title>Demcizumab/Demcizumab Arm (Arm 3)</title>
            <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), demcizumab plus pemetrexed (4 cycles)</description>
          </group>
        </group_list>
        <measure>
          <title>To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.</title>
          <description>Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="28"/>
                <count group_id="O3" value="29"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete response (CR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial response (PR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="13"/>
                    <measurement group_id="O2" value="10"/>
                    <measurement group_id="O3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable disease (SD)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive disease (PD)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not evaluable (NE)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Missing</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>The Kaplan-Meier method was used to estimate both the survival curves and the median survival time. The 95% confidence interval (CI) for the median survival time was calculated. A p-value for treatment effect was generated using a stratified Cox proportional hazards model.</groups_desc>
            <non_inferiority_type>Superiority</non_inferiority_type>
            <non_inferiority_desc>Based on RECIST v1.1. Response outcomes from an assessment done anytime less than Day 35 were considered as not evaluable unless the response assessment was progress disease.</non_inferiority_desc>
            <p_value>=0.0401</p_value>
            <method>Log Rank</method>
            <param_type>Hazard Ratio (HR)</param_type>
            <param_value>0.04</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>.013</ci_lower_limit>
            <ci_upper_limit>.095</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected at every weekly study visit from randomization until 30 days after the termination visit for up to approximately 26 months.</time_frame>
      <desc>All reported adverse events were mapped to standard MedDRA coding terms, grouped by system organ class and preferred term and tabulated by treatment arm.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo/Placebo Arm (Arm 1)</title>
          <description>Placebo plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="E2">
          <title>Demcizumab/Placebo Arm (Arm 2)</title>
          <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), placebo plus pemetrexed (4 cycles)</description>
        </group>
        <group group_id="E3">
          <title>Demcizumab/Demcizumab Arm (Arm 3)</title>
          <description>Demcizumab plus pemetrexed and carboplatin (4 cycles), pemetrexed (4 cycles), demcizumab plus pemetrexed (4 cycles)</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pericardial effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pancreatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Pyrexia</sub_title>
                <description>administration site conditions</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>General physical health deterioration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Performance status decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Gastroenteritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Influenza</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Lung infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Respiratory tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Ejection fraction decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pathological fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Cancer pain</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Metastases to liver</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Cervical cord compression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (17.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="25" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="29" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="11" subjects_affected="11" subjects_at_risk="25"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E3" events="8" subjects_affected="8" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutropenia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Febrile neutropenia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus tachycardia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Vertigo</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Lacrimation increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="18" subjects_affected="18" subjects_at_risk="25"/>
                <counts group_id="E2" events="18" subjects_affected="18" subjects_at_risk="28"/>
                <counts group_id="E3" events="14" subjects_affected="14" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="25"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E3" events="11" subjects_affected="11" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="9" subjects_affected="9" subjects_at_risk="25"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="28"/>
                <counts group_id="E3" events="11" subjects_affected="11" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="25"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E3" events="13" subjects_affected="13" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Stomatitis</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Abdominal pain</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspepsia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="15" subjects_affected="15" subjects_at_risk="25"/>
                <counts group_id="E2" events="16" subjects_affected="16" subjects_at_risk="28"/>
                <counts group_id="E3" events="12" subjects_affected="12" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Asthenia</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="25"/>
                <counts group_id="E2" events="28" subjects_affected="10" subjects_at_risk="28"/>
                <counts group_id="E3" events="29" subjects_affected="9" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="6" subjects_affected="6" subjects_at_risk="28"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Oedema peripheral</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Malaise</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Brain natriuretic peptide increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="28"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Platelet count decreased</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neutrophil count decreased</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Weight decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Decreased appetite</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="4" subjects_affected="4" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="25"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypomagnesaemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hyperkalaemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Musculoskeletal chest pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="25"/>
                <counts group_id="E2" events="11" subjects_affected="11" subjects_at_risk="28"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="8" subjects_affected="8" subjects_at_risk="25"/>
                <counts group_id="E2" events="9" subjects_affected="9" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" subjects_affected="8" subjects_at_risk="25"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="5" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" events="7" subjects_affected="7" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnoea</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E3" events="9" subjects_affected="9" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="6" subjects_affected="6" subjects_at_risk="25"/>
                <counts group_id="E2" events="8" subjects_affected="8" subjects_at_risk="28"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="5" subjects_affected="5" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Haemoptysis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Rhinorrhoea</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="25"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Dyspnoea exertional</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Pulmonary hypertension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="25"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="7" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E3" events="6" subjects_affected="6" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Alopecia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="25"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="14" subjects_affected="14" subjects_at_risk="28"/>
                <counts group_id="E3" events="12" subjects_affected="12" subjects_at_risk="29"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="25"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="29"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Manager, Regulatory Affairs</name_or_title>
      <organization>OncoMed Pharmaceuticals, Inc.</organization>
      <phone>6509958322</phone>
      <email>imran.chaudhry@oncomed.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02259582
org study id: M18-007
nct id: NCT02259582
lead sponsor: 
collaborator: 
has dmc: Yes
A randomized, double-blind, 3-arm (1:1:1) study in subjects with first-line Stage IV
      non-squamous NSCLC. The purpose is to test the efficacy and safety of demcizumab, when given
      in combination with carboplatin and pemetrexed compared to placebo. The administration of
      carboplatin and pemetrexed is a standard treatment for patients with non-squamous non-small
      cell lung cancer.
Patients will be enrolled at centers in North America, Western Europe, Australia and New
      Zealand. Up to 28 days (4 weeks) prior to treatment.

      If enrolled in the study, you will receive intravenous (in the vein) infusions of demcizumab
      (or placebo), carboplatin, and pemetrexed administered on the same day, every 21 days for 4
      cycles, or until it has been shown that your cancer has gotten worse. If your physician
      decides to delay treatment with one of the agents due to side effects, the other agents may
      still be administered as scheduled. After 4 cycles, if you have stable or improved disease,
      you will continue to receive pemetrexed once every 21 days as maintenance therapy. After 8
      cycles, if you have stable or improved disease, you may receive demcizumab (or placebo),
      every 21 days for 4 more cycles.

      You will undergo assessments every 6 weeks to determine the status of your disease.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: To Compare the Investigator-assessed (RECIST) v1.1 Response Rate in the Treatment Arms.
time frame: Response assessment data was collected until the subject started alternative anti-cancer treatment or developed progressive disease, whichever occurred first, assessed up to approximately 26 months.
description: Investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 response rate (unconfirmed) in placebo/placebo arm to demcizumab/placebo arm and demcizumab/demcizumab arm combined in subjects with first-line stage IV non-small cell lung cancer (NSCLC). Response rate was based on Investigator-assessed best-overall-response (BOR) and was defined as the best unconfirmed response determined by RECIST version 1.1 recorded from the start of the treatment until disease progression in the following order of importance: CR, PR , SD, progressive disease (PD), not evaluable, or missing.
arm group label: Arm 1 Pem, carbo, placebo x 4 cycles
arm group type: Placebo Comparator
description: Pemetrexed (500 mg/m2),carboplatin (area under the concentration-time curve of 6 mg/mL x min) once every 21 days X 4 cycles, pemetrexed maintenance and placebo starting at Day 84
arm group label: Arm 2 Pem, carbo x 4 cycles, one course of dem
arm group type: Active Comparator
description: Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, one course of demcizumab 5mg/kg, maintenance pemetrexed + placebo starting on Day 84
arm group label: Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
arm group type: Active Comparator
description: Pemetrexed (500 mg/m2), carboplatin (area under the concentration-time curve of 6 mg/mL x min) x 4 cycles, maintenance pemetrexed starting on Day 84. 2 courses of demcizumab 5 mg/kg
intervention type: Drug
intervention name: Pemetrexed
arm group label: Arm 1 Pem, carbo, placebo x 4 cycles
arm group label: Arm 2 Pem, carbo x 4 cycles, one course of dem
arm group label: Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
intervention type: Drug
intervention name: Carboplatin
arm group label: Arm 1 Pem, carbo, placebo x 4 cycles
arm group label: Arm 2 Pem, carbo x 4 cycles, one course of dem
arm group label: Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
intervention type: Drug
intervention name: demcizumab
arm group label: Arm 2 Pem, carbo x 4 cycles, one course of dem
arm group label: Arm 3 pem, carbo, dem x 4 cycles, dem retreatment
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: No
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country: Australia
country: Belgium
country: Italy
country: Spain
country: United States
responsible party type: Sponsor
mesh term: Lung Neoplasms
mesh term: Carboplatin
mesh term: Pemetrexed
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 