<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/NCT03767348</url>
  </required_header>
  <id_info>
    <org_study_id>RPL-001-16</org_study_id>
    <nct_id>NCT03767348</nct_id>
  </id_info>
  <brief_title>Study of RP1 Monotherapy and RP1 in Combination With Nivolumab</brief_title>
  <acronym>IGNYTE</acronym>
  <official_title>An Open-Label, Multicenter, Phase 1/2 Study of RP1 as a Single Agent and in Combination With PD1 Blockade in Patients With Solid Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Replimune Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Replimune 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>
      RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1&#xD;
      alone and in combination with nivolumab in adult subjects with advanced and/or refractory&#xD;
      solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose&#xD;
      (RP2D), as well as to evaluate preliminary efficacy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly&#xD;
      destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open&#xD;
      label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to&#xD;
      evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of&#xD;
      RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory&#xD;
      solid tumors. The study will include a dose escalation phase for single agent RP1, an&#xD;
      expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified&#xD;
      tumor types for the combination therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 20, 2017</start_date>
  <completion_date type="Anticipated">November 2024</completion_date>
  <primary_completion_date type="Anticipated">November 2024</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percentage of adverse events (AEs)</measure>
    <time_frame>26 months</time_frame>
    <description>Percentage of subjects with adverse events (AEs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of serious adverse events (SAEs)</measure>
    <time_frame>26 months</time_frame>
    <description>Percentage of subjects with serious adverse events (SAEs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of dose limiting toxicities (DLTs)</measure>
    <time_frame>26 months</time_frame>
    <description>Percentage of subjects with dose limiting toxicities (DLTs)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Percentage of overall response rate (ORR)</measure>
    <time_frame>26 months</time_frame>
    <description>Percentage of overall response rate (ORR) for all participants</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1</measure>
    <time_frame>20 weeks</time_frame>
    <description>Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Percentage of biologic activity</measure>
    <time_frame>20 weeks</time_frame>
    <description>Percentage of subjects with biological activity determined by tumor biopsies and biomarker data</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage subjects with detectable RP1</measure>
    <time_frame>20 weeks</time_frame>
    <description>Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of complete response (CR)</measure>
    <time_frame>26 months</time_frame>
    <description>Percentage of subjects with a complete response (CR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median duration of response</measure>
    <time_frame>26 months</time_frame>
    <description>Median duration of response of subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median progression-free survival</measure>
    <time_frame>26 months</time_frame>
    <description>Median duration of progression-free survival of subjects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median overall survival</measure>
    <time_frame>26 months</time_frame>
    <description>Median overall survival rate of subjects</description>
  </secondary_outcome>
  <number_of_arms>10</number_of_arms>
  <enrollment type="Anticipated">340</enrollment>
  <condition>Cancer</condition>
  <condition>Melanoma (Skin)</condition>
  <condition>Mismatch Repair Deficiency</condition>
  <condition>Microsatellite Instability</condition>
  <condition>Non-melanoma Skin Cancer</condition>
  <condition>Cutaneous Melanoma</condition>
  <condition>NSCLC</condition>
  <arm_group>
    <arm_group_label>Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose expansion of RP1 and nivolumab (IV) in superficial tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial tumors with nivolumab (IV)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in melanoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in NMSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>RP1</intervention_name>
    <description>Genetically modified herpes simplex type 1 virus</description>
    <arm_group_label>Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors</arm_group_label>
    <arm_group_label>Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors</arm_group_label>
    <arm_group_label>Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors</arm_group_label>
    <arm_group_label>Dose expansion of RP1 and nivolumab (IV) in superficial tumors</arm_group_label>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors</arm_group_label>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in NMSC</arm_group_label>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in melanoma</arm_group_label>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma</arm_group_label>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC</arm_group_label>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>nivolumab</intervention_name>
    <description>anti-PD-1 monoclonal antibody</description>
    <arm_group_label>Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors</arm_group_label>
    <arm_group_label>Dose expansion of RP1 and nivolumab (IV) in superficial tumors</arm_group_label>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors</arm_group_label>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in NMSC</arm_group_label>
    <arm_group_label>RP1 (IT) and nivolumab (IV) in melanoma</arm_group_label>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma</arm_group_label>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC</arm_group_label>
    <arm_group_label>RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC</arm_group_label>
    <other_name>Opdivo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1.&#xD;
&#xD;
          -  At least one measurable and injectable lesion&#xD;
&#xD;
          -  Have provided a former tumor pathology specimen or be willing to supply a new tumor&#xD;
             sample from a biopsy&#xD;
&#xD;
          -  Have a predicted life expectancy of ≥ 3 months&#xD;
&#xD;
          -  Measurable disease, according to Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             v1.1 criteria&#xD;
&#xD;
          -  Subjects with MSI-H or dMMR tumors: has diagnosis of MSI-H or metatstatic dMMR tumor&#xD;
             (according to protocol definition) who has progressed on prior anti-PD1/PD-L1 therapy.&#xD;
&#xD;
          -  Subjects with NMSC: has diagnosis of locally advanced or metastatic NMSC that are not&#xD;
             considered treatable by surgery including basal cell carcinoma, cutaneous squamous&#xD;
             cell carcinoma, basosquamous carcinoma, Merkel cell carcinoma and other non-melanoma&#xD;
             skin cancers (per protocol). Patients must have received 8 weeks of anti-PD1/PD-L1 as&#xD;
             their last line of therapy and progressed while on treatment.&#xD;
&#xD;
          -  Subjects with anti-PD1 failed cutaneous melanoma: has confirmed progressive disease&#xD;
             while on anti-PD1 treatment for at least 8 weeks and documented BRAF mutation status&#xD;
&#xD;
          -  Subjects with anti-PD1 failed NSCLC: must have failed prior treatment, including&#xD;
             PD1/PD-L1 directed therapy administered either as monotherapy or in combination with&#xD;
             platinum-based chemotherapy or anti-CTLA-4. The most recent treatment given must have&#xD;
             included an anti-PD1/PD-L1 directed therapy with radiologic disease progression on or&#xD;
             after treatment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with an oncolytic therapy&#xD;
&#xD;
          -  History of viral infections according to the protocol&#xD;
&#xD;
          -  Prior complications with herpes infections&#xD;
&#xD;
          -  Chronic use of anti-virals&#xD;
&#xD;
          -  Uncontrolled/untreated brain metastasis&#xD;
&#xD;
          -  History of interstitial lung disease&#xD;
&#xD;
          -  History of non-infectious pneumonitis&#xD;
&#xD;
          -  History of clinically significant cardiovascular 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>Jeannie Hou, MD</last_name>
    <role>Study Director</role>
    <affiliation>Replimune Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Clinical Trials at Replimune</last_name>
    <phone>1-781-222-9570</phone>
    <email>Clinicaltrials@replimune.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University of Birmingham Alabama</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35294</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Banner MD Anderson Cancer Center</name>
      <address>
        <city>Gilbert</city>
        <state>Arizona</state>
        <zip>85234</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jenesse Moffett</last_name>
    </contact>
    <investigator>
      <last_name>Jiaxin Niu, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Mahesh Seetharam, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Carti Cancer Center</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Issam Makhoul, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>UC San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>University of Southern California</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gino In, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>UCLA</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Danell Johnson</last_name>
    </contact>
    <investigator>
      <last_name>Bartosz Chmielowski, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California, Irvine</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>John Fruehauf, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of California- San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Melissa Chow</last_name>
    </contact>
    <investigator>
      <last_name>Katy Tsai, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Sylvester Comprehensive Cancer Center- University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Estelamari Rodriguez, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Iowa-Cancer Center Research</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mariel McKay</last_name>
    </contact>
    <investigator>
      <last_name>Mohammed Milhem, MBBS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>James Graham Brown Cancer Center- University of Louisville</name>
      <address>
        <city>Louisville</city>
        <state>Kentucky</state>
        <zip>40202</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Stacy Baum</last_name>
    </contact>
    <investigator>
      <last_name>Jason Chesney, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Robert McWilliams, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Atlantic Health System</name>
      <address>
        <city>Morristown</city>
        <state>New Jersey</state>
        <zip>07960</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Eric Whitman, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>New York University Clinical Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Anna Pavlick, DO</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Rochester Medical Center</name>
      <address>
        <city>Rochester</city>
        <state>New York</state>
        <zip>14642</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Delaney Dretto</last_name>
    </contact>
    <contact_backup>
      <last_name>Janice Cifelli</last_name>
    </contact_backup>
    <investigator>
      <last_name>Rachael Turner, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Duke Cancer Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Georgia Beasley, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Trisha Wise-Draper, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>MUSC Health</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>John Kaczmar, MD</last_name>
    </contact>
  </location>
  <location>
    <facility>
      <name>West Cancer Center</name>
      <address>
        <city>Germantown</city>
        <state>Tennessee</state>
        <zip>38138</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Alisa Harber</last_name>
    </contact>
    <investigator>
      <last_name>Ari Vanderwalde, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The University of Texas MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Michael Wong, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Eccles Outpatient Care Center- Oncology Clinical Trials</name>
      <address>
        <city>Murray</city>
        <state>Utah</state>
        <zip>84107</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tawnya Bowles</last_name>
    </contact>
    <investigator>
      <last_name>Tawnya Bowles, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Intermountain Cancer Center- Saint George Cancer Center</name>
      <address>
        <city>Saint George</city>
        <state>Utah</state>
        <zip>84790</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Angi Cox</last_name>
    </contact>
    <investigator>
      <last_name>Terence Rhodes, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Seattle Cancer Care Alliance- University of Washington</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98109</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Katie Kim</last_name>
    </contact>
    <investigator>
      <last_name>Evan Hall, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin-Carbone Cancer Center</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>CHU Besancon - Hopital Jean Minjoz</name>
      <address>
        <city>Besançon</city>
        <zip>25000</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Nardin Charlee, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Bergonié</name>
      <address>
        <city>Bordeaux</city>
        <zip>33076</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Antoine Italiano, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU Dijon</name>
      <address>
        <city>Dijon</city>
        <zip>21079</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Sophie Dalac-Rat, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Centre Léon Bérard Lyon</name>
      <address>
        <city>Lyon</city>
        <zip>69373</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Mona AMINI-ADLE, MD</last_name>
    </contact>
    <investigator>
      <last_name>Mona AMINI-ADLE, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Service de Dermatologie et Cancerologie Cutanee Hopital de la Timone</name>
      <address>
        <city>Marseille</city>
        <zip>13005</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Caroline Gaudy, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>CHU de Nice Hôpital l'Archet</name>
      <address>
        <city>Nice</city>
        <zip>06200</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Henri Montaudie, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis APHP</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Céleste Lebbe, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Villejuif</city>
        <zip>94800</zip>
        <country>France</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Judith Michels, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Charité (Campus Benjamin Franklin)</name>
      <address>
        <city>Berlin</city>
        <zip>12203</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Sebastian Ochsenreither, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University Hospital Essen, Klinik für Dermatologie</name>
      <address>
        <city>Essen</city>
        <zip>45147</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Dirk Schadendorf, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Kiel (UKSH), Dep. of Dermatology</name>
      <address>
        <city>Kiel</city>
        <zip>24105</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Katharina Kahler, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Uniklinik Marburg</name>
      <address>
        <city>Marburg</city>
        <zip>35043</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Martin Gschnell, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <zip>08035</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Eva Couselo Munoz, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Clinic Barcelona</name>
      <address>
        <city>Barcelona</city>
        <zip>08036</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ana Arance Fernández, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Institut Catala D'Oncologia - Hospital Duran I</name>
      <address>
        <city>Barcelona</city>
        <zip>08908</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Juan Liberal Martin, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clínica Universidad de Navarra (Madrid)</name>
      <address>
        <city>Madrid</city>
        <zip>28027</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Miguel Fernández de Sanmamed</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Arrixaca</name>
      <address>
        <city>Murcia</city>
        <zip>30120</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Pablo Cerezuela, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Clinica Universitaria de Navarra</name>
      <address>
        <city>Pamplona</city>
        <zip>31008</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Miguel Gutiérrez Sanmamed, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen del Rocio</name>
      <address>
        <city>Sevilla</city>
        <zip>41013</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ana Gill, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hospital General Universitario de Valencia</name>
      <address>
        <city>Valencia</city>
        <zip>46014</zip>
        <country>Spain</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Alfonso Jaime Berrocal, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>University of Leeds- Teaching Hospital</name>
      <address>
        <city>Leeds</city>
        <state>England</state>
        <zip>LS97TF</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Adel Samson, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Oxford University Hospitals NHS Trust</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Mark R Middleton, MD,PhD,FRCP</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beatson West of Scotland Cancer Center</name>
      <address>
        <city>Glasgow</city>
        <state>Scotland</state>
        <zip>G12 0YN</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Patricia Roxburgh, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>The Clatterbridge Cancer Centre NHS Foundation Trust</name>
      <address>
        <city>Bebington</city>
        <state>Wirral</state>
        <zip>CH634JY</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Joseph Sacco, MRCP, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Royal Marsden Hospital</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Kevin Harrington, BSc FRCP PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Southampton General Hospital</name>
      <address>
        <city>Southampton</city>
        <zip>SO16 6YD</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <investigator>
      <last_name>Ioannis Karydis, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>France</country>
    <country>Germany</country>
    <country>Spain</country>
    <country>United Kingdom</country>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>December 5, 2018</study_first_submitted>
  <study_first_submitted_qc>December 5, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 6, 2018</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Oncolytic virus</keyword>
  <keyword>Oncolytic Immuno-gene therapy</keyword>
  <keyword>Non-melanoma Skin Cancer</keyword>
  <keyword>Cutaneous Melanoma</keyword>
  <keyword>Anti-PD1 failed</keyword>
  <keyword>Melanoma (skin)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
    <mesh_term>Skin Neoplasms</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>Nivolumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03767348
org study id: RPL-001-16
nct id: NCT03767348
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
RPL-001-16 is a Phase 1/2, open label, dose escalation and expansion clinical study of RP1
      alone and in combination with nivolumab in adult subjects with advanced and/or refractory
      solid tumors, to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose
      (RP2D), as well as to evaluate preliminary efficacy.
RP1 is a genetically modified herpes simplex type 1 virus that is designed to directly
      destroy tumors and to generate an anti-tumor immune response. This is a Phase 1/2, open
      label, multicenter, dose escalation and expansion, first-in-human (FIH) clinical study to
      evaluate the safety and tolerability, biodistribution, shedding, and preliminary efficacy of
      RP1 alone and in combination with nivolumab in adult subjects with advanced and/or refractory
      solid tumors. The study will include a dose escalation phase for single agent RP1, an
      expansion phase with a combination of RP1 and nivolumab and a Phase 2 portion in specified
      tumor types for the combination therapy.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Percentage of adverse events (AEs)
time frame: 26 months
description: Percentage of subjects with adverse events (AEs)
measure: Percentage of serious adverse events (SAEs)
time frame: 26 months
description: Percentage of subjects with serious adverse events (SAEs)
measure: Percentage of dose limiting toxicities (DLTs)
time frame: 26 months
description: Percentage of subjects with dose limiting toxicities (DLTs)
measure: Percentage of overall response rate (ORR)
time frame: 26 months
description: Percentage of overall response rate (ORR) for all participants
measure: Maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1
time frame: 20 weeks
description: Assess the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of RP1 based on the safety and response data collected during Phase 1 Escalation
measure: Percentage of biologic activity
time frame: 20 weeks
description: Percentage of subjects with biological activity determined by tumor biopsies and biomarker data
measure: Percentage subjects with detectable RP1
time frame: 20 weeks
description: Data gathered from blood, urine, swabs of injection site, dressings, and oral mucosa to determine the shedding and biodistribution of RP1
measure: Percentage of complete response (CR)
time frame: 26 months
description: Percentage of subjects with a complete response (CR)
measure: Median duration of response
time frame: 26 months
description: Median duration of response of subjects
measure: Median progression-free survival
time frame: 26 months
description: Median duration of progression-free survival of subjects
measure: Median overall survival
time frame: 26 months
description: Median overall survival rate of subjects
arm group label: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors
arm group type: Experimental
description: Dose escalation of RP1 alone in 3 cohorts with IT injections in superficial tumors
arm group label: Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors
arm group type: Experimental
description: Dose escalation of RP1 alone in 3 cohorts with IT injections in deep/visceral tumors
arm group label: Dose expansion of RP1 and nivolumab (IV) in superficial tumors
arm group type: Experimental
description: Doses of RP1 (IT) in superficial tumors with nivolumab (IV)
arm group label: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
arm group type: Experimental
description: Doses of RP1 (IT) in deep/visceral tumors with nivolumab (IV)
arm group label: RP1 (IT) and nivolumab (IV) in melanoma
arm group type: Experimental
description: Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with melanoma
arm group label: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
arm group type: Experimental
description: Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with MSI-H or dMMR solid tumors
arm group label: RP1 (IT) and nivolumab (IV) in NMSC
arm group type: Experimental
description: Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
arm group type: Experimental
description: Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with cutaneous melanoma who have been previously treated with anti-PD1 therapy
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
arm group type: Experimental
description: Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non-melanoma skin cancer who have been previously treated with anti-PD1/PD-L1 therapy
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
arm group type: Experimental
description: Doses of RP1 (IT) in superficial or deep tumors with nivolumab (IV) in subjects with non small cell lung cancer who have been previously treated with anti-PD1/PD-L1 therapy
intervention type: Biological
intervention name: RP1
description: Genetically modified herpes simplex type 1 virus
arm group label: Dose escalation of RP1 by intratumoral (IT) injection in deep/visceral tumors
arm group label: Dose escalation of RP1 by intratumoral (IT) injection in superficial tumors
arm group label: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
arm group label: Dose expansion of RP1 and nivolumab (IV) in superficial tumors
arm group label: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
arm group label: RP1 (IT) and nivolumab (IV) in NMSC
arm group label: RP1 (IT) and nivolumab (IV) in melanoma
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
intervention type: Biological
intervention name: nivolumab
description: anti-PD-1 monoclonal antibody
arm group label: Dose expansion of RP1 and nivolumab (IV) in deep/visceral tumors
arm group label: Dose expansion of RP1 and nivolumab (IV) in superficial tumors
arm group label: RP1 (IT) and nivolumab (IV) in MSI-H/dMMR solid tumors
arm group label: RP1 (IT) and nivolumab (IV) in NMSC
arm group label: RP1 (IT) and nivolumab (IV) in melanoma
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1 Failed Cutaneous Melanoma
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NMSC
arm group label: RP1(IT) and nivolumab (IV) in anti-PD1/PD-L1 Failed NSCLC
other name: Opdivo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeannie Hou, MD
role: Study Director
affiliation: Replimune Inc.
last name: Clinical Trials at Replimune
phone: 1-781-222-9570
email: Clinicaltrials@replimune.com
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
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status: Recruiting
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facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
facility: 
status: Recruiting
investigator: 
country: France
country: Germany
country: Spain
country: United Kingdom
country: United States
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Skin Neoplasms
mesh term: Microsatellite Instability
mesh term: Nivolumab
sharing ipd: Undecided