<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/NCT02243371</url>
  </required_header>
  <id_info>
    <org_study_id>J14113</org_study_id>
    <secondary_id>ADU-CL-06</secondary_id>
    <secondary_id>IRB00043936</secondary_id>
    <nct_id>NCT02243371</nct_id>
  </id_info>
  <brief_title>GVAX Pancreas Vaccine (With CY) and CRS-207 With or Without Nivolumab</brief_title>
  <official_title>A Randomized Phase 2 Study of the Safety, Efficacy, and Immune Response of GVAX Pancreas Vaccine (With Cyclophosphamide) and CRS-207 With or Without Nivolumab in Patients With Previously Treated Metastatic Pancreatic Adenocarcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stand Up To Cancer</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Aduro Biotech, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>American Association for Cancer Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Lustgarten Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to compare the overall survival (OS) of subjects with&#xD;
      previously treated metastatic pancreatic cancer treated with cyclophosphamide&#xD;
      (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects&#xD;
      treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2, 2015</start_date>
  <completion_date type="Actual">July 21, 2017</completion_date>
  <primary_completion_date type="Actual">July 21, 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>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>2 years and 7 months</time_frame>
    <description>OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity</measure>
    <time_frame>2 years and 7 months</time_frame>
    <description>When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients</measure>
    <time_frame>2 years and 7 months</time_frame>
    <description>PFS is defined as the number of months from the date of randomization to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is &gt;20% increase in sum of diameters of target lesions, Stable Disease (SD) is &lt;30% decrease or &lt;20% increase in sum of diameters of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients</measure>
    <time_frame>2 years and 7 months</time_frame>
    <description>irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is &gt;20% increase in tumor burden compared with nadir, Stable Disease (SD) is &lt;30% decrease in tumor burden compared with baseline or &lt;20% increase in tumor burden compared to nadir.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients</measure>
    <time_frame>2 years and 7 months</time_frame>
    <description>Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is &gt;20% increase in sum of diameters of target lesions, Stable Disease (SD) is &lt;30% decrease or &lt;20% increase in sum of diameters of target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients</measure>
    <time_frame>2 years and 7 months</time_frame>
    <description>Per RECIST 1.1 criteria, PR is defined as =&gt;30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration</measure>
    <time_frame>120 days</time_frame>
    <description>Number of participants with stable or responding (&lt;50% increase of serum CA19-9 concentration) at 120 days.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">93</enrollment>
  <condition>Previously Treated Metastatic Adenocarcinoma of the Pancreas</condition>
  <arm_group>
    <arm_group_label>Arm A: CY/ GVAX/ CRS-207/ nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: CY/ GVAX/ CRS-207</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CRS-207</intervention_name>
    <description>1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6</description>
    <arm_group_label>Arm A: CY/ GVAX/ CRS-207/ nivolumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CRS-207</intervention_name>
    <description>1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6</description>
    <arm_group_label>Arm B: CY/ GVAX/ CRS-207</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>nivolumab</intervention_name>
    <description>3 mg/kg administered IV on Day 1 of Cycles 1-6</description>
    <arm_group_label>Arm A: CY/ GVAX/ CRS-207/ nivolumab</arm_group_label>
    <other_name>BMS-936558; anti-PD-1 mAb</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>GVAX</intervention_name>
    <description>5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2</description>
    <arm_group_label>Arm A: CY/ GVAX/ CRS-207/ nivolumab</arm_group_label>
    <arm_group_label>Arm B: CY/ GVAX/ CRS-207</arm_group_label>
    <other_name>GVAX pancreas vaccine, Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CY</intervention_name>
    <description>200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
    <arm_group_label>Arm A: CY/ GVAX/ CRS-207/ nivolumab</arm_group_label>
    <arm_group_label>Arm B: CY/ GVAX/ CRS-207</arm_group_label>
    <other_name>Cytoxan, Cyclophosphamide</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥18 years.&#xD;
&#xD;
          -  Have histologically- or cytologically-proven adenocarcinoma of the pancreas. Patients&#xD;
             with mixed histology will be excluded.&#xD;
&#xD;
          -  Have metastatic disease.&#xD;
&#xD;
          -  Have failed only 1 prior chemotherapy regimen for metastatic pancreatic cancer.&#xD;
&#xD;
          -  Patients with the presence of at least one measurable lesion.&#xD;
&#xD;
          -  Patients acceptance to have a tumor biopsy of an accessible lesion at baseline and on&#xD;
             treatment if the lesion can be biopsied with acceptable clinical risk (as judged by&#xD;
             the investigator).&#xD;
&#xD;
          -  ECOG performance status 0 or 1.&#xD;
&#xD;
          -  Life expectancy of greater than 3 months.&#xD;
&#xD;
          -  Patients must have adequate organ and marrow function defined by study-specified&#xD;
             laboratory tests.&#xD;
&#xD;
          -  Must use acceptable form of birth control while on study.&#xD;
&#xD;
          -  Ability to understand and willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  known history or evidence of brain metastases.&#xD;
&#xD;
          -  Had surgery within the last 28 days&#xD;
&#xD;
          -  Have received any non-oncology vaccine therapy used for prevention of infectious&#xD;
             diseases including seasonal vaccinations within 28 days of study treatment.&#xD;
&#xD;
          -  Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA4, GVAX or CRS-207&#xD;
&#xD;
          -  Systemic steroids within the last 14 days&#xD;
&#xD;
          -  Use more than 3 g/day of acetaminophen.&#xD;
&#xD;
          -  Patients on immunosuppressive agents.&#xD;
&#xD;
          -  Patients receiving growth factors within the last 14 days&#xD;
&#xD;
          -  Known allergy to both penicillin and sulfa.&#xD;
&#xD;
          -  Severe hypersensitivity reaction to any monoclonal antibody.&#xD;
&#xD;
          -  Have artificial joints or implants that cannot be easily removed&#xD;
&#xD;
          -  Have any evidence of hepatic cirrhosis or clinical or radiographic ascites.&#xD;
&#xD;
          -  Have significant and/or malignant pleural effusion&#xD;
&#xD;
          -  Infection with HIV or hepatitis B or C at screening&#xD;
&#xD;
          -  Significant heart disease&#xD;
&#xD;
          -  Conditions, including alcohol or drug dependence, intercurrent illness, or lack of&#xD;
             sufficient peripheral venous access, that would affect the patient's ability to comply&#xD;
             with study visits and procedures&#xD;
&#xD;
          -  Unable to avoid intimate contact with another individual known to be at high risk of&#xD;
             listeriosis (e.g., newborn infant, pregnant woman, HIV-positive individual) during the&#xD;
             course of CRS-207 treatment until completion of antibiotic regimen.&#xD;
&#xD;
          -  Are pregnant or breastfeeding.&#xD;
&#xD;
          -  Have rapidly progressing disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Dung Le, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Johns Hopkins University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Portland Medical Center</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2020</verification_date>
  <study_first_submitted>September 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 16, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 17, 2014</study_first_posted>
  <results_first_submitted>August 6, 2019</results_first_submitted>
  <results_first_submitted_qc>September 16, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 8, 2019</results_first_posted>
  <last_update_submitted>March 17, 2021</last_update_submitted>
  <last_update_submitted_qc>March 17, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Adenocarcinoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>November 15, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/71/NCT02243371/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>CY/ GVAX/ CRS-207/ Nivolumab</title>
          <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
        </group>
        <group group_id="P2">
          <title>CY/ GVAX/ CRS-207</title>
          <description>CRS-207: 1 × 10^9 CFU administered IV Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="51"/>
                <participants group_id="P2" count="42"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="37"/>
                <participants group_id="P2" count="32"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Progressive Disease (clinic &amp; radio)</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death (unrelated)</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="4"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Adverse Event (unrelated)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lack of Clinical Benefit</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" 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="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>CY/ GVAX/ CRS-207/ Nivolumab</title>
          <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
        </group>
        <group group_id="B2">
          <title>CY/ GVAX/ CRS-207</title>
          <description>CRS-207: 1 × 10^9 CFU administered IV Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
        </group>
        <group group_id="B3">
          <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="51"/>
            <count group_id="B2" value="42"/>
            <count group_id="B3" value="93"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="63.6" spread="8.08"/>
                    <measurement group_id="B2" value="63.2" spread="9.28"/>
                    <measurement group_id="B3" value="63.4" spread="8.60"/>
                  </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="14"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="24"/>
                    <measurement group_id="B3" value="61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="46"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="84"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="7"/>
                  </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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="10"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="44"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="77"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </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_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Overall Survival (OS)</title>
        <description>OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).</description>
        <time_frame>2 years and 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival (OS)</title>
          <description>OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.88" lower_limit="4.73" upper_limit="8.64"/>
                    <measurement group_id="O2" value="6.11" lower_limit="3.52" upper_limit="7.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity</title>
        <description>When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.</description>
        <time_frame>2 years and 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity</title>
          <description>When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.</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="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients</title>
        <description>PFS is defined as the number of months from the date of randomization to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is &gt;20% increase in sum of diameters of target lesions, Stable Disease (SD) is &lt;30% decrease or &lt;20% increase in sum of diameters of target lesions.</description>
        <time_frame>2 years and 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients</title>
          <description>PFS is defined as the number of months from the date of randomization to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is &gt;20% increase in sum of diameters of target lesions, Stable Disease (SD) is &lt;30% decrease or &lt;20% increase in sum of diameters of target lesions.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.23" lower_limit="2.14" upper_limit="2.33"/>
                    <measurement group_id="O2" value="2.17" lower_limit="2.00" upper_limit="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients</title>
        <description>irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is &gt;20% increase in tumor burden compared with nadir, Stable Disease (SD) is &lt;30% decrease in tumor burden compared with baseline or &lt;20% increase in tumor burden compared to nadir.</description>
        <time_frame>2 years and 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients</title>
          <description>irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is &gt;20% increase in tumor burden compared with nadir, Stable Disease (SD) is &lt;30% decrease in tumor burden compared with baseline or &lt;20% increase in tumor burden compared to nadir.</description>
          <units>months</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.27" lower_limit="2.17" upper_limit="2.33"/>
                    <measurement group_id="O2" value="2.23" lower_limit="2.10" upper_limit="2.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients</title>
        <description>Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is &gt;20% increase in sum of diameters of target lesions, Stable Disease (SD) is &lt;30% decrease or &lt;20% increase in sum of diameters of target lesions.</description>
        <time_frame>2 years and 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients</title>
          <description>Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =&gt;30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is &gt;20% increase in sum of diameters of target lesions, Stable Disease (SD) is &lt;30% decrease or &lt;20% increase in sum of diameters of target lesions.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.20" lower_limit="2.10" upper_limit="2.33"/>
                    <measurement group_id="O2" value="2.20" lower_limit="2.00" upper_limit="2.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients</title>
        <description>Per RECIST 1.1 criteria, PR is defined as =&gt;30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.</description>
        <time_frame>2 years and 7 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients</title>
          <description>Per RECIST 1.1 criteria, PR is defined as =&gt;30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.</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="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration</title>
        <description>Number of participants with stable or responding (&lt;50% increase of serum CA19-9 concentration) at 120 days.</description>
        <time_frame>120 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
          <group group_id="O2">
            <title>Arm B: CY/ GVAX/ CRS-207</title>
            <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration</title>
          <description>Number of participants with stable or responding (&lt;50% increase of serum CA19-9 concentration) at 120 days.</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="51"/>
                <count group_id="O2" value="42"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>2 years and 7 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A: CY/ GVAX/ CRS-207/ Nivolumab</title>
          <description>CRS-207: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
nivolumab: 3 mg/kg administered IV on Day 1 of Cycles 1-6&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
        </group>
        <group group_id="E2">
          <title>Arm B: CY/ GVAX/ CRS-207</title>
          <description>CRS-207: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6&#xD;
GVAX: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2&#xD;
CY: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2</description>
        </group>
      </group_list>
      <serious_events>
        <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="45" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="36" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>THROMBOCYTOPENIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>MYOCARDITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>DIARRHOEA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>LISTERIA SEPSIS</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="51"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>HYPERGLYCAEMIA</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>PNEUMONITIS</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="51"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="46" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>LYMPHOPENIA</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>SINUS TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>TACHYCARDIA</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>NAUSEA</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="19" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VOMITING</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>VACCINATION SITE ERYTHEMA</sub_title>
                <counts group_id="E1" subjects_affected="46" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="40" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE INDURATION</sub_title>
                <counts group_id="E1" subjects_affected="41" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="31" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>CHILLS</sub_title>
                <counts group_id="E1" subjects_affected="42" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE PRURITUS</sub_title>
                <counts group_id="E1" subjects_affected="36" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="30" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>PYREXIA</sub_title>
                <counts group_id="E1" subjects_affected="38" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="27" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE PAIN</sub_title>
                <counts group_id="E1" subjects_affected="34" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="29" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE DISCOMFORT</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>FATIGUE</sub_title>
                <counts group_id="E1" subjects_affected="23" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="12" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>INFLUENZA LIKE ILLNESS</sub_title>
                <counts group_id="E1" subjects_affected="13" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE OEDEMA</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE SWELLING</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE VESICLES</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE REACTION</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>VACCINATION SITE BRUISING</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>PAIN</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>ALANINE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>ASPARTATE AMINOTRANSFERASE INCREASED</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>ARTHRALGIA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>MYALGIA</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>HEADACHE</sub_title>
                <counts group_id="E1" subjects_affected="10" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>DIZZINESS</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>HYPERTENSION</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="42"/>
              </event>
              <event>
                <sub_title>HYPOTENSION</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="51"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="42"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Dung Le, MD</name_or_title>
      <organization>The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</organization>
      <phone>443-287-0002</phone>
      <email>dle@jhmi.edu</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/NCT02243371
org study id: J14113
secondary id: ADU-CL-06
secondary id: IRB00043936
nct id: NCT02243371
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
The primary objective of this study is to compare the overall survival (OS) of subjects with
      previously treated metastatic pancreatic cancer treated with cyclophosphamide
      (CY)/nivolumab/GVAX pancreas vaccine followed by nivolumab/CRS-207 (Arm A) to subjects
      treated with CY/GVAX pancreas vaccine followed by CRS-207 (Arm B).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Overall Survival (OS)
time frame: 2 years and 7 months
description: OS will be measured from date of randomization until death or end of followup (OS will be censored on the date the subject was last known to be alive for subjects without documentation of death at the time of analysis).
measure: Number of Patients Experiencing a Grade 3 or Above Treatment-related Toxicity
time frame: 2 years and 7 months
description: When calculating the incidence of AEs, each AE (as defined by NCI CTCAE v4.03) will be counted only once for a given subject.
measure: Progression-free Survival (PFS) in Metastatic Pancreatic Cancer Patients
time frame: 2 years and 7 months
description: PFS is defined as the number of months from the date of randomization to disease progression (progressive disease [PD] or relapse from complete response [CR] as assessed using RECIST 1.1 criteria) or death due to any cause. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
measure: Immune-related Progression-free Survival (irPFS) by IRRC in Metastatic Pancreatic Cancer Patients
time frame: 2 years and 7 months
description: irPFS is defined as the number of months from the date of randomization to disease progression (PD or relapse from CR as assessed using irRC RECIST 1.1 criteria) or death due to any cause. Per irRC criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in tumor burden compared with baseline, Progressive Disease (PD) is >20% increase in tumor burden compared with nadir, Stable Disease (SD) is <30% decrease in tumor burden compared with baseline or <20% increase in tumor burden compared to nadir.
measure: Time to Progression (TTP) by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
time frame: 2 years and 7 months
description: Time to progression (TTP) is defined as the time from randomization to the date of documented disease progression as defined by RECIST 1.1 criteria. Individuals are censored at the date of the last radiological assessment that occurs prior to any of the following: death, switch to another anti-cancer therapy, or end of follow-up. Individuals without follow-up or baseline measurements are censored at 1 day. Per RECIST 1.1 criteria, CR = disappearance of all target lesions, Partial Response (PR) is =>30% decrease in sum of diameters of target lesions, Progressive Disease (PD) is >20% increase in sum of diameters of target lesions, Stable Disease (SD) is <30% decrease or <20% increase in sum of diameters of target lesions.
measure: Number of Participants With Partial Response (PR) or Complete Response (CR) as Defined by RECIST 1.1 in Metastatic Pancreatic Cancer Patients
time frame: 2 years and 7 months
description: Per RECIST 1.1 criteria, PR is defined as =>30% decrease in sum of diameters of target lesions and CR is the disappearance of all target lesions.
measure: Tumor Marker Kinetics (CA 19-9) in Patients With Baseline Abnormal Levels as Measured by Number of Participants With Stable or Responding CA19-9 Concentration
time frame: 120 days
description: Number of participants with stable or responding (<50% increase of serum CA19-9 concentration) at 120 days.
arm group label: Arm A: CY/ GVAX/ CRS-207/ nivolumab
arm group type: Experimental
arm group label: Arm B: CY/ GVAX/ CRS-207
arm group type: Experimental
intervention type: Biological
intervention name: CRS-207
description: 1 × 10^9 CFU administered IV on Day 2 of Cycles 3-6
arm group label: Arm A: CY/ GVAX/ CRS-207/ nivolumab
intervention type: Biological
intervention name: CRS-207
description: 1 × 10^9 CFU administered IV on Day 1 of Cycles 3-6
arm group label: Arm B: CY/ GVAX/ CRS-207
intervention type: Drug
intervention name: nivolumab
description: 3 mg/kg administered IV on Day 1 of Cycles 1-6
arm group label: Arm A: CY/ GVAX/ CRS-207/ nivolumab
other name: BMS-936558; anti-PD-1 mAb
intervention type: Biological
intervention name: GVAX
description: 5x10^8 cells administered in 6 intradermal injections on Day 2 of Cycles 1 and 2
arm group label: Arm A: CY/ GVAX/ CRS-207/ nivolumab
arm group label: Arm B: CY/ GVAX/ CRS-207
other name: GVAX pancreas vaccine, Panc 10.05 pcDNA-1/GM-Neo, Panc 6.03 pcDNA-1/GM-Neo
intervention type: Drug
intervention name: CY
description: 200 mg/m^2 administered IV on Day 1 of Cycles 1 and 2
arm group label: Arm A: CY/ GVAX/ CRS-207/ nivolumab
arm group label: Arm B: CY/ GVAX/ CRS-207
other name: Cytoxan, Cyclophosphamide
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dung Le, MD
role: Principal Investigator
affiliation: Johns Hopkins University
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Adenocarcinoma
mesh term: Cyclophosphamide
mesh term: Nivolumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 