<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/NCT03294083</url>
  </required_header>
  <id_info>
    <org_study_id>JX594-REN026</org_study_id>
    <nct_id>NCT03294083</nct_id>
  </id_info>
  <brief_title>A Study of Recombinant Vaccinia Virus in Combination With Cemiplimab for Renal Cell Carcinoma</brief_title>
  <official_title>A Phase 1b/2a Dose-escalation and Safety/Efficacy Evaluation Study of Pexa-Vec (Thymidine Kinase-Deactivated Vaccinia Virus Plus GM-CSF) in Combination With Cemiplimab (REGN2810; Anti-PD-1) in Patients With Metastatic or Unresectable Renal Cell Carcinoma (RCC)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>SillaJen, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Regeneron Pharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>SillaJen, Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1b/2a, open-label, multi-center, dose-escalation and safety/efficacy&#xD;
      evaluation trial of Pexa-Vec plus Cemiplimab in patients with metastatic or unresectable&#xD;
      renal cell carcinoma (RCC). The trial consists of a dose-escalation stage, where the maximum&#xD;
      feasible dose of Pexa-Vec in combination with Cemiplimab will be determined, followed by an&#xD;
      expansion stage. During the expansion patients will receive Cemiplimab alone or in&#xD;
      combination with Pexa-Vec, which will be administered either through intravenous (IV) or&#xD;
      intratumoral (IT) injection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">June 7, 2018</start_date>
  <completion_date type="Anticipated">November 2023</completion_date>
  <primary_completion_date type="Anticipated">August 2023</primary_completion_date>
  <phase>Phase 1/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>Maximum tolerated dose(MTD) / Maximum feasible dose (MFD)</measure>
    <time_frame>36 days after first treatment</time_frame>
    <description>MTD/MFD of Pexa-Vec administered by IV infusion in combination with Cemiplimab</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV Cemiplimab</measure>
    <time_frame>From date of first treatment until 28 days after last treatment</time_frame>
    <description>Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate</measure>
    <time_frame>Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months</time_frame>
    <description>Evaluate anti-tumor activity and efficacy of IV or IT Pexa-Vec combined with IV Cemiplimab with respect to overall response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best radiographic response</measure>
    <time_frame>Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months</time_frame>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">89</enrollment>
  <condition>Renal Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Part 1, Dose escalation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pexa-Vec will be administered via IV infusion at a dose of 3 x 10^8 pfu once per week for 4 treatments. Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 1 x 10^9 pfu.&#xD;
Cemiplimab will be administered via IV infusion every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments.&#xD;
Cemiplimab will be administered via IV infusion every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2-Arm B, Cemiplimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Cemiplimab will be administered via IV infusion every 3 weeks.&#xD;
At disease progression, Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will continue every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pexa-Vec will be administered via IV infusion once per week for 4 treatments.&#xD;
Cemiplimab will be administered via IV infusion every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Pexa-Vec will be administered via IV infusion once per week for 4 treatments.&#xD;
Cemiplimab will be administered via IV infusion every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Pexastimogene Devacirepvec (Pexa-Vec)</intervention_name>
    <description>Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells</description>
    <arm_group_label>Part 1, Dose escalation</arm_group_label>
    <arm_group_label>Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab</arm_group_label>
    <arm_group_label>Part 2-Arm B, Cemiplimab</arm_group_label>
    <arm_group_label>Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab</arm_group_label>
    <arm_group_label>Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab</arm_group_label>
    <other_name>JX-594</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Cemiplimab</intervention_name>
    <description>Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)</description>
    <arm_group_label>Part 1, Dose escalation</arm_group_label>
    <arm_group_label>Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab</arm_group_label>
    <arm_group_label>Part 2-Arm B, Cemiplimab</arm_group_label>
    <arm_group_label>Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab</arm_group_label>
    <arm_group_label>Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Histologically or cytologically confirmed metastatic or unresectable clear cell renal&#xD;
             cell carcinoma (ccRCC)&#xD;
&#xD;
          -  Part 2 Arm D ONLY: Patients must be refractory to anti PD-1 or anti-PD-L1 (either as&#xD;
             monotherapy or in-combination with other approved checkpoint inhibitors or targeted&#xD;
             therapies according to their approved label) and patients must meet all of the&#xD;
             following criteria:&#xD;
&#xD;
               1. Received treatment of approved anti PD-1 or anti-PD-L1 (dosed per label of the&#xD;
                  country providing the clinical site) for at least 6 weeks. History of anti-PD-L1&#xD;
                  only is not allowed.&#xD;
&#xD;
               2. Progressive disease after anti PD-1 or anti-PD-L1 will be defined according to&#xD;
                  RECIST 1.1. The initial evidence of progressive disease is to be confirmed by a&#xD;
                  second assessment, no less than 4 weeks from the date of the first documented&#xD;
                  progressive disease, in the absence of rapid clinical progression. (This&#xD;
                  determination is made by the Investigator; the Sponsor will collect imaging scans&#xD;
                  for retrospective analysis. Once progressive disease is confirmed, the initial&#xD;
                  date of progressive disease documentation will be considered the date of disease&#xD;
                  progression).&#xD;
&#xD;
               3. Documented disease progression within 12 weeks of the last dose of anti PD-1 or&#xD;
                  anti-PD-L1. Patients who were re-treated or on maintenance with anti-PD-1 or&#xD;
                  anti-PD-L1 will be allowed to enter the study as long as there is documented&#xD;
                  progressive disease within 12 weeks of the last treatment date.&#xD;
&#xD;
          -  Naive to systemic therapy for RCC or have progressed after, or were intolerant of,&#xD;
             prior systemic therapy.&#xD;
&#xD;
          -  Measurable disease based on RECIST 1.1 criteria. Tumor lesions situated in a&#xD;
             previously irradiated area are considered measurable if progression has been&#xD;
             demonstrated in such lesions&#xD;
&#xD;
          -  Karnofsky performance status of 70-100&#xD;
&#xD;
          -  Age ≥20 years old (or appropriate age of consent for the region)&#xD;
&#xD;
          -  Adequate hematological, hepatic, and renal function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Known significant immunodeficiency due to underlying illness (e.g., human&#xD;
             immunodeficiency virus [HIV] / acquired immune deficiency syndrome [AIDS]) and/or&#xD;
             immune-suppressive medication including high-dose corticosteroids&#xD;
&#xD;
          -  Part 2 only: Arm A,B,C: Prior treatment with any anti-cancer immunotherapy, including&#xD;
             therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent (prior IL-2 or interferon&#xD;
             allowed) . For Part 1: patients are excluded if they were intolerant to anti-PD-1 or&#xD;
             anti-PD-L1 targeted therapies&#xD;
&#xD;
          -  Major surgery within 4 weeks of study treatment (minor surgical procedures are&#xD;
             allowed)&#xD;
&#xD;
          -  Ongoing severe inflammatory skin condition requiring prior medical treatment&#xD;
&#xD;
          -  History of eczema requiring prior medical treatment&#xD;
&#xD;
          -  Tumor(s) invading a major vascular structure (e.g., carotid artery) or other key&#xD;
             anatomical structure (e.g., pulmonary airway) OR viable central nervous system&#xD;
             malignancy&#xD;
&#xD;
          -  Clinically significant and/or rapidly accumulating ascites, pericardial and/or pleural&#xD;
             effusions.&#xD;
&#xD;
          -  Symptomatic cardiovascular disease, including but not limited to significant coronary&#xD;
             artery disease (e.g., requiring angioplasty or stenting) or congestive heart failure&#xD;
             within the preceding 12 months.&#xD;
&#xD;
          -  Asymptomatic cardiovascular disease (current or past history) unless cardiology&#xD;
             consultation and clearance has been obtained for study participation.&#xD;
&#xD;
          -  Inability to suspend treatment with anti-hypertensive medication for 48 hours prior to&#xD;
             and 48 hours after all Pexa-Vec treatments&#xD;
&#xD;
          -  Use of interferon/pegylated interferon (PEG-IFN) or ribavirin that cannot be&#xD;
             discontinued within 14 days prior to any Pexa-Vec dose&#xD;
&#xD;
          -  Known active Hepatitis B or Hepatitis C&#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>Site 2644 University of California, Irvine</name>
      <address>
        <city>Irvine</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2641 University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2643 Washington University</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2646 The Ohio State University</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2632 Flinders Medical Centre</name>
      <address>
        <city>Bedford Park</city>
        <zip>SA5042</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2612 Kyungpook National University Chilgok Hospital</name>
      <address>
        <city>Daegu</city>
        <zip>41404</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2616 Chungnam National University Hospital</name>
      <address>
        <city>Daejeon</city>
        <zip>35015</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2618 Chonnam National University Hwasun Hospital</name>
      <address>
        <city>Gwangju</city>
        <zip>58128</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2622 Gachon University Gil Medical Center</name>
      <address>
        <city>Incheon</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2613 Dong-A University Hospital</name>
      <address>
        <city>Pusan</city>
        <zip>49201</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2619 Pusan National University Hospital</name>
      <address>
        <city>Pusan</city>
        <zip>49241</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2620 Seoul National University Bundang Hospital</name>
      <address>
        <city>Seongnam-si</city>
        <zip>13620</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2617 CHA University, CHA Bundang Medical Center</name>
      <address>
        <city>Seongnam</city>
        <zip>35015</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2615 Korea University Anam Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>02841</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2610 Severance Hospital, Yonsei University Health System</name>
      <address>
        <city>Seoul</city>
        <zip>03722</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2623 Ajou University Hospital</name>
      <address>
        <city>Suwon</city>
        <zip>16499</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2625 Wonju Severance Christian Hospital</name>
      <address>
        <city>Wŏnju</city>
        <zip>50612</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Site 2624 Pusan National University Yangsan Hospital</name>
      <address>
        <city>Yangsan</city>
        <zip>50612</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Korea, Republic of</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>September 19, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 26, 2017</study_first_posted>
  <last_update_submitted>October 26, 2022</last_update_submitted>
  <last_update_submitted_qc>October 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cancer</keyword>
  <keyword>Renal cell carcinoma</keyword>
  <keyword>Clear cell renal cell carcinoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vaccinia</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Renal Cell</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cemiplimab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03294083
org study id: JX594-REN026
nct id: NCT03294083
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1b/2a, open-label, multi-center, dose-escalation and safety/efficacy
      evaluation trial of Pexa-Vec plus Cemiplimab in patients with metastatic or unresectable
      renal cell carcinoma (RCC). The trial consists of a dose-escalation stage, where the maximum
      feasible dose of Pexa-Vec in combination with Cemiplimab will be determined, followed by an
      expansion stage. During the expansion patients will receive Cemiplimab alone or in
      combination with Pexa-Vec, which will be administered either through intravenous (IV) or
      intratumoral (IT) injection.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Maximum tolerated dose(MTD) / Maximum feasible dose (MFD)
time frame: 36 days after first treatment
description: MTD/MFD of Pexa-Vec administered by IV infusion in combination with Cemiplimab
measure: Severity and frequency of adverse events to determine safety of Pexa-Vec administered by IV infusions or IT injections in combination with IV Cemiplimab
time frame: From date of first treatment until 28 days after last treatment
description: Safety will be determined by assessing the severity and frequency of adverse events and laboratory toxicity using CTCAE v4.03
measure: Overall response rate
time frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
description: Evaluate anti-tumor activity and efficacy of IV or IT Pexa-Vec combined with IV Cemiplimab with respect to overall response rate (ORR) per Response Evaluation Criteria In Solid Tumors (RECIST 1.1)
measure: Progression free survival
time frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
measure: Disease control rate
time frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
measure: Best radiographic response
time frame: Every 9 weeks, then every 12 weeks after 1 year until date of first documented progression, up to 72 months
measure: Overall survival
time frame: Every 9 weeks, then every 12 weeks after 1 year until date of death from any cause, up to 72 months
arm group label: Part 1, Dose escalation
arm group type: Experimental
description: Pexa-Vec will be administered via IV infusion at a dose of 3 x 10^8 pfu once per week for 4 treatments. Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 1 x 10^9 pfu.
Cemiplimab will be administered via IV infusion every 3 weeks.
arm group label: Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab
arm group type: Experimental
description: Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments.
Cemiplimab will be administered via IV infusion every 3 weeks.
arm group label: Part 2-Arm B, Cemiplimab
arm group type: Experimental
description: Cemiplimab will be administered via IV infusion every 3 weeks.
At disease progression, Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will continue every 3 weeks.
arm group label: Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab
arm group type: Experimental
description: Pexa-Vec will be administered via IV infusion once per week for 4 treatments.
Cemiplimab will be administered via IV infusion every 3 weeks.
arm group label: Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab
arm group type: Experimental
description: Pexa-Vec will be administered via IV infusion once per week for 4 treatments.
Cemiplimab will be administered via IV infusion every 3 weeks.
intervention type: Biological
intervention name: Pexastimogene Devacirepvec (Pexa-Vec)
description: Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells
arm group label: Part 1, Dose escalation
arm group label: Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab
arm group label: Part 2-Arm B, Cemiplimab
arm group label: Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab
arm group label: Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab
other name: JX-594
intervention type: Biological
intervention name: Cemiplimab
description: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1)
arm group label: Part 1, Dose escalation
arm group label: Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab
arm group label: Part 2-Arm B, Cemiplimab
arm group label: Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab
arm group label: Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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facility: 
facility: 
facility: 
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country: Australia
country: Korea, Republic of
country: United States
responsible party type: Sponsor
mesh term: Vaccinia
mesh term: Carcinoma
mesh term: Carcinoma, Renal Cell
mesh term: Cemiplimab