<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/NCT03836352</url>
  </required_header>
  <id_info>
    <org_study_id>P1719-SUR-Z11</org_study_id>
    <secondary_id>Keynote 903</secondary_id>
    <nct_id>NCT03836352</nct_id>
  </id_info>
  <brief_title>Study of an Immunotherapeutic, DPX-Survivac, in Combination With Low Dose Cyclophosphamide &amp; Pembrolizumab, in Subjects With Selected Advanced &amp; Recurrent Solid Tumors</brief_title>
  <official_title>A Phase 2, Open-label, Multicenter, Study of an Immunotherapeutic Treatment, DPX-Survivac in Combination With Low Dose Cyclophosphamide and Pembrolizumab, in Subjects With Selected Advanced and Recurrent Solid Tumours.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>ImmunoVaccine Technologies, Inc. (IMV Inc.)</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>ImmunoVaccine Technologies, Inc. (IMV Inc.)</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will assess the safety and efficacy of DPX-Survivac and low dose cyclophosphamide&#xD;
      with pembrolizumab in subjects with selected advanced and recurrent solid tumours.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a Phase 2 with safety lead-in study to assess the safety and efficacy of&#xD;
      DPX-Survivac, low dose cyclophosphamide, and pembrolizumab combination therapy in subjects&#xD;
      with selected advanced and recurrent solid tumours. Two ovarian cancer arms will be recruited&#xD;
      and randomized in this study, one with and one without cyclophosphamide. All other cohorts&#xD;
      will be single arm, receiving treatment with the triple combination.&#xD;
&#xD;
      Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments&#xD;
      before the study moves to the expansion phase. Once the safety lead-in is completed, the five&#xD;
      cohorts will be expanded to recruit additional subjects following a Simon two stage design.&#xD;
      Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">December 21, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <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>Efficacy as measured by objective response rate</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Centrally evaluated using RECIST v1.1</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Safety as measured by the rate of adverse events</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Centrally evaluated using iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Approximately 24 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Cell mediated immunology</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>As measured by antigen specific immune response in peripheral blood</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes in immune cell infiltration</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>As measured by multiplex immunohistochemistry</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">184</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Hepatocellular Carcinoma</condition>
  <condition>Non-small Cell Lung Cancer</condition>
  <condition>Bladder Cancer</condition>
  <condition>Microsatellite Instability-High</condition>
  <arm_group>
    <arm_group_label>Arm 1 (All cohorts)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DPX-Survivac, Cyclophosphamide, Pembrolizumab</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2 (Ovarian cohort only)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>DPX-Survivac, Pembrolizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>DPX-Survivac</intervention_name>
    <description>SubQ injection (q9w)</description>
    <arm_group_label>Arm 1 (All cohorts)</arm_group_label>
    <arm_group_label>Arm 2 (Ovarian cohort only)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>PO (BID)</description>
    <arm_group_label>Arm 1 (All cohorts)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>IV Infusion (q3w)</description>
    <arm_group_label>Arm 1 (All cohorts)</arm_group_label>
    <arm_group_label>Arm 2 (Ovarian cohort only)</arm_group_label>
    <other_name>MK-3475</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          -  Subjects with advanced or metastatic solid tumours who have completed treatment with&#xD;
             first line therapy:&#xD;
&#xD;
               1. Epithelial ovarian, fallopian tube, or peritoneal cancer&#xD;
&#xD;
               2. Hepatocellular carcinoma&#xD;
&#xD;
               3. Non-small cell lung cancer&#xD;
&#xD;
               4. Urothelial cancer&#xD;
&#xD;
               5. Microsatellite instability high solid tumours, other than the above indications&#xD;
&#xD;
          -  Radiologic and/or biochemical evidence of disease progression&#xD;
&#xD;
          -  Completion of pre-treatment tumour biopsy&#xD;
&#xD;
          -  Must have measurable disease by RECIST v1.1&#xD;
&#xD;
          -  Ambulatory with an ECOG 0-1&#xD;
&#xD;
          -  Life expectancy ≥ 6 months&#xD;
&#xD;
          -  Meet protocol-specified laboratory requirements&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Chemotherapy or immunotherapy within treatment within 28 days of start of study&#xD;
             treatment&#xD;
&#xD;
          -  Radiotherapy within treatment within 2 weeks of start of study treatment&#xD;
&#xD;
          -  Prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent&#xD;
             directed to another stimulatory or co-inhibitory T cell receptor where subject was&#xD;
             discontinued from that treatment due to a Grade 3 or higher immune-related toxicity&#xD;
&#xD;
          -  For NSCLC subjects: Known EGFR mutations or ALK rearrangements&#xD;
&#xD;
          -  Prior receipt of survivin-based vaccine(s) and/or immunotherapies&#xD;
&#xD;
          -  Concurrent second malignancy other than non-melanoma skin cancer, cervical carcinoma&#xD;
             in situ, or controlled bladder cancer&#xD;
&#xD;
          -  Clinical ascites or pleural fluid that cannot be managed&#xD;
&#xD;
          -  Malignant bowel obstruction or recent history of bowel obstruction&#xD;
&#xD;
          -  For OvCa, subjects with any single lesion greater than 5 cm&#xD;
&#xD;
          -  Autoimmune disease requiring treatment within the last two years (except replacement&#xD;
             therapy)&#xD;
&#xD;
          -  Recent history of thyroiditis&#xD;
&#xD;
          -  Any history of (non-infectious) pneumonitis that required steroid therapy or current&#xD;
             pneumonitis&#xD;
&#xD;
          -  Presence of a serious acute or chronic infection&#xD;
&#xD;
          -  Active CNS metastases and/or carcinomatous meningitis&#xD;
&#xD;
          -  GI condition that might limit absorption of oral agents&#xD;
&#xD;
          -  Allogenic tissue/solid organ transplant&#xD;
&#xD;
          -  Other serious intercurrent chronic or acute illness, including myocardial infarction&#xD;
             or cerebrovascular event within 6 months&#xD;
&#xD;
          -  Ongoing treatment with steroid therapy or other immunosuppressive&#xD;
&#xD;
          -  Receipt of live attenuated vaccines&#xD;
&#xD;
          -  Acute or chronic skin and/or microvascular disorders&#xD;
&#xD;
          -  Edema or lymphedema in the lower limbs &gt; grade 2&#xD;
&#xD;
          -  Severe hypersensitivity (≥ Grade 3) to pembrolizumab&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>The University of Arizona Cancer Center</name>
      <address>
        <city>Tucson</city>
        <state>Arizona</state>
        <zip>58724</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cedars Sinai Medical Center: Samuel Oschin Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90048</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boca Raton Regional Hospital, Lynn Cancer Institute</name>
      <address>
        <city>Boca Raton</city>
        <state>Florida</state>
        <zip>33486</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hematology Oncology Associates of the Treasure Coast</name>
      <address>
        <city>Port Saint Lucie</city>
        <state>Florida</state>
        <zip>34952</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Comprehensive Hematology and Oncology</name>
      <address>
        <city>Saint Petersburg</city>
        <state>Florida</state>
        <zip>33709</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Winship Cancer Institute: The Emory Clinic</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>James Brown Graham Cancer Center:University of Louisville Hospital</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ochsner Cancer Institute</name>
      <address>
        <city>New Orleans</city>
        <state>Louisiana</state>
        <zip>70121</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Allina Health, Virginia Piper Cancer Institute</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55407</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Christus St. Vincent Regional Cancer Center</name>
      <address>
        <city>Santa Fe</city>
        <state>New Mexico</state>
        <zip>87505</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Montefiore Medical Center</name>
      <address>
        <city>Bronx</city>
        <state>New York</state>
        <zip>10461</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>NYU Winthrop Hospital</name>
      <address>
        <city>Mineola</city>
        <state>New York</state>
        <zip>11501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Toledo</name>
      <address>
        <city>Toledo</city>
        <state>Ohio</state>
        <zip>43614</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mary Crowley Cancer Research Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75230</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William Osler Health System</name>
      <address>
        <city>Brampton</city>
        <state>Ontario</state>
        <zip>L6R3J7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Juravinski Cancer Center</name>
      <address>
        <city>Hamilton</city>
        <state>Ontario</state>
        <zip>L8V 5C2</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Southlake Regional Health Center</name>
      <address>
        <city>Newmarket</city>
        <state>Ontario</state>
        <zip>L3Y 2P9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ottawa Hospital</name>
      <address>
        <city>Ottawa</city>
        <state>Ontario</state>
        <zip>K1H 8L6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sunnybrook Research Institute</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre hospitalier de l'Université de Montréal (CHUM)</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H2X 0A9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>McGill University Health Center</name>
      <address>
        <city>Montreal</city>
        <state>Quebec</state>
        <zip>H4A 3J1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>CHU de Québec-Université Laval</name>
      <address>
        <city>Québec</city>
        <state>Quebec</state>
        <zip>G1R 2J6</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>February 7, 2019</study_first_submitted>
  <study_first_submitted_qc>February 7, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 11, 2019</study_first_posted>
  <last_update_submitted>March 28, 2022</last_update_submitted>
  <last_update_submitted_qc>March 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 31, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>T cell activation</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Ovarian</keyword>
  <keyword>Hepatocellular Carcinoma</keyword>
  <keyword>Non-small Cell Lung</keyword>
  <keyword>Bladder</keyword>
  <keyword>Microsatellite Instability-High</keyword>
  <keyword>Survivin</keyword>
  <keyword>Anti-PD-1</keyword>
  <keyword>MK-3475</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma, Hepatocellular</mesh_term>
    <mesh_term>Microsatellite Instability</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <pending_results>
    <submitted>September 11, 2023</submitted>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03836352
org study id: P1719-SUR-Z11
secondary id: Keynote 903
nct id: NCT03836352
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study will assess the safety and efficacy of DPX-Survivac and low dose cyclophosphamide
      with pembrolizumab in subjects with selected advanced and recurrent solid tumours.
This study is a Phase 2 with safety lead-in study to assess the safety and efficacy of
      DPX-Survivac, low dose cyclophosphamide, and pembrolizumab combination therapy in subjects
      with selected advanced and recurrent solid tumours. Two ovarian cancer arms will be recruited
      and randomized in this study, one with and one without cyclophosphamide. All other cohorts
      will be single arm, receiving treatment with the triple combination.

      Up to 20 subjects, from any cohort, will be enrolled to assess the safety of study treatments
      before the study moves to the expansion phase. Once the safety lead-in is completed, the five
      cohorts will be expanded to recruit additional subjects following a Simon two stage design.
      Enrollment in the ovarian cancer cohort will be randomized 1:1 into two arms.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy as measured by objective response rate
time frame: Approximately 24 months
description: Centrally evaluated using RECIST v1.1
measure: Safety as measured by the rate of adverse events
time frame: Approximately 24 months
description: Using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0
measure: Objective response rate
time frame: Approximately 24 months
description: Centrally evaluated using iRECIST
measure: Duration of response
time frame: Approximately 24 months
measure: Disease control rate
time frame: Approximately 24 months
measure: Progression Free Survival
time frame: Approximately 24 months
measure: Overall survival
time frame: Approximately 24 months
measure: Cell mediated immunology
time frame: Approximately 24 months
description: As measured by antigen specific immune response in peripheral blood
measure: Changes in immune cell infiltration
time frame: Approximately 24 months
description: As measured by multiplex immunohistochemistry
arm group label: Arm 1 (All cohorts)
arm group type: Experimental
description: DPX-Survivac, Cyclophosphamide, Pembrolizumab
arm group label: Arm 2 (Ovarian cohort only)
arm group type: Experimental
description: DPX-Survivac, Pembrolizumab
intervention type: Other
intervention name: DPX-Survivac
description: SubQ injection (q9w)
arm group label: Arm 1 (All cohorts)
arm group label: Arm 2 (Ovarian cohort only)
intervention type: Drug
intervention name: Cyclophosphamide
description: PO (BID)
arm group label: Arm 1 (All cohorts)
intervention type: Drug
intervention name: Pembrolizumab
description: IV Infusion (q3w)
arm group label: Arm 1 (All cohorts)
arm group label: Arm 2 (Ovarian cohort only)
other name: MK-3475
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
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country: Canada
country: United States
responsible party type: Sponsor
mesh term: Carcinoma, Hepatocellular
mesh term: Microsatellite Instability
mesh term: Cyclophosphamide
mesh term: Pembrolizumab
submitted: September 11, 2023