<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/NCT03259425</url>
  </required_header>
  <id_info>
    <org_study_id>HCI102346</org_study_id>
    <nct_id>NCT03259425</nct_id>
  </id_info>
  <brief_title>Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma</brief_title>
  <official_title>Phase II Neoadjuvant Trial of Nivolumab in Combination With HF10 Oncolytic Viral Therapy in Resectable Stage IIIB, IIIC, IVM1a Melanoma (Neo-NivoHF10)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Utah</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Takara Bio Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Utah</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 is a single-arm, open label, Phase II study evaluating the safety and efficacy of&#xD;
      neoadjuvant Nivolumab and HF10 in resectable stage IIIB, IIIC, and IVM1a melanoma.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    DSMC Recommendation&#xD;
  </why_stopped>
  <start_date type="Actual">January 3, 2018</start_date>
  <completion_date type="Actual">September 25, 2020</completion_date>
  <primary_completion_date type="Actual">September 21, 2018</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a single-arm, open label, Phase II</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Pathological Response</measure>
    <time_frame>at time of surgery (12 weeks)</time_frame>
    <description>Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, participants underwent definitive surgery. A percent viable tumor was assessed semi-quantitatively in the definitive surgical resection specimen by estimating the proportion of residual tumor in relation to the total tumor area and reported as percentage viability. A pathologic complete response was defined as no viable residual melanoma cells in the surgical specimen. A major pathologic response was defined as &lt;50% viable tumor cells. A minor pathologic response was defined as 50% or greater viable tumor cells, including specimens that had 100% viability at surgery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery</measure>
    <time_frame>up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)</time_frame>
    <description>Recurrence after surgery will be assessed by radiologic scans and confirmed by biopsy. Death within the follow-up period is also considered recurrence. This outcome will report the number of participants who were alive and who had no disease recurrence during the follow-up period.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival: Number of Participants Alive One Year After Completing Adjuvant Nivolumab</measure>
    <time_frame>up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)</time_frame>
    <description>Participants were followed for survival for one year after completion of adjuvant nivolumab. Adjuvant nivolumab was planned for up to one year of adjuvant treatment after surgery. This objective reports the number of participants who were alive one year after the completion of adjuvant nivolumab.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category</measure>
    <time_frame>12 weeks from baseline to surgery</time_frame>
    <description>Participants were assessed radiographically and clinically prior to study start and prior to surgery. Lesions were measured, and lesions that were at least 10 mm on CT, MRI, caliper, or ruler, or at least 20 mm on x-ray were documented as Target Lesions. Lesions that did not meet criteria to be Target Lesions were documented as Non-Target lesions. Measurements of Target Lesions were summed. Change in Target Lesion measurements was used to determine response by RECIST 1.1 criteria. Complete Response (CR) indicates a disappearance of all lesions. Partial Response (PR) indicates at least 30% decrease in the sum of Target Lesions. Progressive Disease (PD) indicates at least 20% increase in the sum of Target Lesions, or the appearance of one or more new lesions after baseline. Stable Disease (SD) is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Objective was reported as number of participants within each response category.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Complete Surgical Resection</measure>
    <time_frame>Within 28 days after Day 84</time_frame>
    <description>Participants' surgical samples were assessed by a pathologist after surgery to determine if complete surgical resection was achieved after neo-adjuvant treatment with nivolumab and HF10. R0 indicates a complete surgical resection was achieved and means no residual tumor was detected after after surgery. R1 means microscopic tumor was detected and a complete surgical resection was not achieved.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events Related to HF10 Treatment</measure>
    <time_frame>throughout HF10 treatment (up to 84 days)</time_frame>
    <description>Participants were monitored for adverse events (AEs) during treatment with HF10 using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to HF10 treatment are grouped by grade 1-2 and grade 3-5 AEs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adverse Events Related to Nivolumab Treatment</measure>
    <time_frame>throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery)</time_frame>
    <description>Participants were monitored for adverse events (AEs) during treatment with nivolumab using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to nivolumab treatment are grouped by grade 1-2 and grade 3-5 AEs.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Melanoma</condition>
  <arm_group>
    <arm_group_label>Nivolumab and HF10, all participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.</description>
    <arm_group_label>Nivolumab and HF10, all participants</arm_group_label>
    <other_name>OPDIVO</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HF10</intervention_name>
    <description>1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections. All eligible tumors except one will be treated with HF10 up to the maximum volume allowed. The untreated tumor will be used as an untreated control lesion.</description>
    <arm_group_label>Nivolumab and HF10, all participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be &gt;18 years or older.&#xD;
&#xD;
          -  Participants must have stage IIIB, IIIC, or IVM1a (equivalent staging at time of&#xD;
             enrollment via American Joint Committee on Cancer (AJCC) 7th edition) metastatic&#xD;
             melanoma which is eligible for complete surgical resection.&#xD;
&#xD;
          -  Prior systemic, regional and radiation anticancer therapies must have been completed&#xD;
             at least three months prior to enrollment. Prior therapies (including anti-programmed&#xD;
             death (PD)-1 inhibitors) are allowed provided three months have elapsed from last&#xD;
             dose.&#xD;
&#xD;
          -  Participants must be a candidate for intralesional therapy.&#xD;
&#xD;
          -  At least 1 injectable cutaneous, subcutaneous, or nodal melanoma lesion &gt; 10 mm in&#xD;
             longest diameter OR&#xD;
&#xD;
          -  Multiple injectable melanoma lesions which in aggregate have a longest diameter of &gt;&#xD;
             10 mm AND&#xD;
&#xD;
          -  Must have no known bleeding diathesis or coagulopathy that would make intratumoral&#xD;
             injection unsafe.&#xD;
&#xD;
          -  Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status&#xD;
             of 0 or 1.&#xD;
&#xD;
          -  Serum (LDH) level &lt; 1.5 upper limit of normal (ULN) within 28 days prior to&#xD;
             enrollment.&#xD;
&#xD;
          -  Participants have adequate organ function within 28 days prior to enrollment, as&#xD;
             defined in the protocol&#xD;
&#xD;
          -  Men and women of childbearing potential must agree to use adequate contraception from&#xD;
             the time of consent through 7 months after final nivolumab study treatment.&#xD;
&#xD;
          -  Females of childbearing potential must have a negative urine or serum pregnancy test&#xD;
             within 1 week prior to the start of treatment.&#xD;
&#xD;
          -  Participants must be able to provide informed consent and willing to sign an approved&#xD;
             consent form that conforms to federal and institutional guidelines.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Participants with active visceral, central nervous system, or any bone metastases&#xD;
             melanoma (Stage IVM1b or IVM1c).&#xD;
&#xD;
          -  Participants whose primary diagnosis was ocular melanoma.&#xD;
&#xD;
          -  Participants receiving anti-herpes medication (i.e., acyclovir, famciclovir, or&#xD;
             valacyclovir) within 1 week prior to initiating HF10 treatment. Participants may not&#xD;
             require intermittent or chronic systemic (intravenous or oral) treatment with an&#xD;
             antiherpetic drug other than intermittent topical use.&#xD;
&#xD;
          -  Participants who have an active herpetic skin lesion(s) or prior complications of&#xD;
             herpes simplex virus (HSV)-1 infection.&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements, as determined by the investigator.&#xD;
&#xD;
          -  Medical history of autoimmune disease (e.g. Crohn's disease, ulcerative colitis) or&#xD;
             other disease requiring systemic glucocorticoid or immunosuppressive therapy. Subjects&#xD;
             who receive daily steroid replacement therapy serve as an exception to this rule.&#xD;
             Daily prednisone equivalent at doses up to 10 mg would qualify.&#xD;
&#xD;
          -  Participants with clinically evident Human Immunodeficiency Virus (HIV), Hepatitis B&#xD;
             Virus (HBV), Hepatitis C Virus (HCV), or Epstein-Barr Virus (EBV) infection are&#xD;
             excluded.&#xD;
&#xD;
          -  Pregnant or breast feeding women; women desiring to become pregnant within the&#xD;
             timeframe of the study are also excluded.&#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>Huntsman Cancer Institute</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84112</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>August 18, 2017</study_first_submitted>
  <study_first_submitted_qc>August 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 23, 2017</study_first_posted>
  <results_first_submitted>September 20, 2019</results_first_submitted>
  <results_first_submitted_qc>September 20, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">October 10, 2019</results_first_posted>
  <last_update_submitted>June 9, 2022</last_update_submitted>
  <last_update_submitted_qc>June 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 13, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Resectable Stage IIIB, IIIC, and IVM1a</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 22, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/25/NCT03259425/Prot_SAP_003.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Nivolumab and HF10 (All Participants)</title>
          <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Surgery</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Disease progression to an extent that didn't allow surgery</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Nivolumab and HF10 (All Participants )</title>
          <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="7"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64.14" spread="22.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="71" lower_limit="18" upper_limit="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Tumor Viability Percentage</title>
          <description>Following a pre-treatment biopsy at baseline, a pathologist reviewed the tumor tissue collected and estimated tumor viability, expressed as a percentage of viable tumor from 0-100%. This is reported here as a count of participants with greater than 90% tumor viability at baseline.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Tumor Viability &gt;= 90%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Tumor Viability &lt; 90%</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Pathological Response</title>
        <description>Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, participants underwent definitive surgery. A percent viable tumor was assessed semi-quantitatively in the definitive surgical resection specimen by estimating the proportion of residual tumor in relation to the total tumor area and reported as percentage viability. A pathologic complete response was defined as no viable residual melanoma cells in the surgical specimen. A major pathologic response was defined as &lt;50% viable tumor cells. A minor pathologic response was defined as 50% or greater viable tumor cells, including specimens that had 100% viability at surgery.</description>
        <time_frame>at time of surgery (12 weeks)</time_frame>
        <population>One of seven participants had progressive disease while receiving neoadjuvant therapy and did not receive surgical resection and therefore per protocol was not assessed for response.</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Pathological Response</title>
          <description>Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, participants underwent definitive surgery. A percent viable tumor was assessed semi-quantitatively in the definitive surgical resection specimen by estimating the proportion of residual tumor in relation to the total tumor area and reported as percentage viability. A pathologic complete response was defined as no viable residual melanoma cells in the surgical specimen. A major pathologic response was defined as &lt;50% viable tumor cells. A minor pathologic response was defined as 50% or greater viable tumor cells, including specimens that had 100% viability at surgery.</description>
          <population>One of seven participants had progressive disease while receiving neoadjuvant therapy and did not receive surgical resection and therefore per protocol was not assessed for response.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Pathologic Complete Response (0% Tumor Viability)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Major Pathologic Response (&lt;50% Tumor Viability)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Minor Pathologic Response (&gt;=50% Tumor Viability)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery</title>
        <description>Recurrence after surgery will be assessed by radiologic scans and confirmed by biopsy. Death within the follow-up period is also considered recurrence. This outcome will report the number of participants who were alive and who had no disease recurrence during the follow-up period.</description>
        <time_frame>up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)</time_frame>
        <population>The participant who did not complete surgery was not followed for post-surgery outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery</title>
          <description>Recurrence after surgery will be assessed by radiologic scans and confirmed by biopsy. Death within the follow-up period is also considered recurrence. This outcome will report the number of participants who were alive and who had no disease recurrence during the follow-up period.</description>
          <population>The participant who did not complete surgery was not followed for post-surgery outcomes.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Overall Survival: Number of Participants Alive One Year After Completing Adjuvant Nivolumab</title>
        <description>Participants were followed for survival for one year after completion of adjuvant nivolumab. Adjuvant nivolumab was planned for up to one year of adjuvant treatment after surgery. This objective reports the number of participants who were alive one year after the completion of adjuvant nivolumab.</description>
        <time_frame>up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)</time_frame>
        <population>The participant who did not complete surgery was not followed for post-surgery outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Overall Survival: Number of Participants Alive One Year After Completing Adjuvant Nivolumab</title>
          <description>Participants were followed for survival for one year after completion of adjuvant nivolumab. Adjuvant nivolumab was planned for up to one year of adjuvant treatment after surgery. This objective reports the number of participants who were alive one year after the completion of adjuvant nivolumab.</description>
          <population>The participant who did not complete surgery was not followed for post-surgery outcomes.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category</title>
        <description>Participants were assessed radiographically and clinically prior to study start and prior to surgery. Lesions were measured, and lesions that were at least 10 mm on CT, MRI, caliper, or ruler, or at least 20 mm on x-ray were documented as Target Lesions. Lesions that did not meet criteria to be Target Lesions were documented as Non-Target lesions. Measurements of Target Lesions were summed. Change in Target Lesion measurements was used to determine response by RECIST 1.1 criteria. Complete Response (CR) indicates a disappearance of all lesions. Partial Response (PR) indicates at least 30% decrease in the sum of Target Lesions. Progressive Disease (PD) indicates at least 20% increase in the sum of Target Lesions, or the appearance of one or more new lesions after baseline. Stable Disease (SD) is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Objective was reported as number of participants within each response category.</description>
        <time_frame>12 weeks from baseline to surgery</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category</title>
          <description>Participants were assessed radiographically and clinically prior to study start and prior to surgery. Lesions were measured, and lesions that were at least 10 mm on CT, MRI, caliper, or ruler, or at least 20 mm on x-ray were documented as Target Lesions. Lesions that did not meet criteria to be Target Lesions were documented as Non-Target lesions. Measurements of Target Lesions were summed. Change in Target Lesion measurements was used to determine response by RECIST 1.1 criteria. Complete Response (CR) indicates a disappearance of all lesions. Partial Response (PR) indicates at least 30% decrease in the sum of Target Lesions. Progressive Disease (PD) indicates at least 20% increase in the sum of Target Lesions, or the appearance of one or more new lesions after baseline. Stable Disease (SD) is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Objective was reported as number of participants within each response category.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Complete Response (CR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Partial Response (PR)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Stable Disease (SD)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Progressive Disease (PD)</title>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Complete Surgical Resection</title>
        <description>Participants' surgical samples were assessed by a pathologist after surgery to determine if complete surgical resection was achieved after neo-adjuvant treatment with nivolumab and HF10. R0 indicates a complete surgical resection was achieved and means no residual tumor was detected after after surgery. R1 means microscopic tumor was detected and a complete surgical resection was not achieved.</description>
        <time_frame>Within 28 days after Day 84</time_frame>
        <population>The participant who did not complete surgery was not followed for post-surgery outcomes.</population>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Complete Surgical Resection</title>
          <description>Participants' surgical samples were assessed by a pathologist after surgery to determine if complete surgical resection was achieved after neo-adjuvant treatment with nivolumab and HF10. R0 indicates a complete surgical resection was achieved and means no residual tumor was detected after after surgery. R1 means microscopic tumor was detected and a complete surgical resection was not achieved.</description>
          <population>The participant who did not complete surgery was not followed for post-surgery outcomes.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>R0 Complete Surgical Resection</title>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>R1 Incomplete Surgical Resection</title>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events Related to HF10 Treatment</title>
        <description>Participants were monitored for adverse events (AEs) during treatment with HF10 using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to HF10 treatment are grouped by grade 1-2 and grade 3-5 AEs.</description>
        <time_frame>throughout HF10 treatment (up to 84 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events Related to HF10 Treatment</title>
          <description>Participants were monitored for adverse events (AEs) during treatment with HF10 using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to HF10 treatment are grouped by grade 1-2 and grade 3-5 AEs.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with G1-2 AEs related to HF10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with G3-5 AEs related to HF10</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adverse Events Related to Nivolumab Treatment</title>
        <description>Participants were monitored for adverse events (AEs) during treatment with nivolumab using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to nivolumab treatment are grouped by grade 1-2 and grade 3-5 AEs.</description>
        <time_frame>throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Nivolumab and HF10 (All Participants)</title>
            <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adverse Events Related to Nivolumab Treatment</title>
          <description>Participants were monitored for adverse events (AEs) during treatment with nivolumab using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to nivolumab treatment are grouped by grade 1-2 and grade 3-5 AEs.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Participants with G1-2 AEs related to Nivolumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Participants with G3-5 AEs related to Nivolumab</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From first dose of study treatment to 30 days after last dose of study treatment (up to 1 year, 8 months)</time_frame>
      <desc>Per protocol: The occurrence of adverse events should be sought by non-directive questioning of the participant at each visit or phone contact during the study. Adverse events also may be detected when they are volunteered by the participant during or between visits or through physical examination, laboratory test, or other assessments.</desc>
      <group_list>
        <group group_id="E1">
          <title>Nivolumab and HF10 (All Participants)</title>
          <description>Nivolumab: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.&#xD;
HF10: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiac disorders - Other, specify</sub_title>
                <description>non-ST-elevation myocardial infarction (NSTEMI), likely demand ischemia</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Heart failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Adrenal insufficiency</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Endocrine disorders - Other, specify</sub_title>
                <description>hypophysitis</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hyponatremia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify</sub_title>
                <description>basosquamous cell carcinoma</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute kidney injury</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Respiratory, thoracic and mediastinal disorders - Other, specify</sub_title>
                <description>pneumonia left lung</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <description>lichenoid eruptive keratoacanthomas; squamous cell carcinoma</description>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Thromboembolic event</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (4.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Endocrine disorders</title>
            <event_list>
              <event>
                <sub_title>Hypothyroidism</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Dry eye</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Toothache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="9" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Flu like symptoms</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Infusion related reaction</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Eye infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Mucosal infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Creatinine increased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Anorexia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dehydration</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Bone pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Joint range of motion decreased</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify</sub_title>
                <description>right 3rd digit papule</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="5" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Nervous system disorders - Other, specify</sub_title>
                <description>numbness of the lower left ear lobe/jaw</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Peripheral motor neuropathy</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Genital edema</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Testicular pain</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hiccups</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hoarseness</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Productive cough</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="6" subjects_affected="5" subjects_at_risk="7"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other, specify</sub_title>
                <description>scalp psoriasis; wasp sting; erythematous plaque; nodular amelanotic area scapha left ear</description>
                <counts group_id="E1" events="7" subjects_affected="3" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Surgical and medical procedures - Other, specify</sub_title>
                <description>shave biopsy of left lateral lower eyelid</description>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="7"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Data Manager, Research Compliance Office</name_or_title>
      <organization>Huntsman Cancer Institute</organization>
      <phone>8015850601</phone>
      <email>compliance@hci.utah.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03259425
org study id: HCI102346
nct id: NCT03259425
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a single-arm, open label, Phase II study evaluating the safety and efficacy of
      neoadjuvant Nivolumab and HF10 in resectable stage IIIB, IIIC, and IVM1a melanoma.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a single-arm, open label, Phase II
primary purpose: Treatment
masking: None (Open Label)
measure: Pathological Response
time frame: at time of surgery (12 weeks)
description: Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, participants underwent definitive surgery. A percent viable tumor was assessed semi-quantitatively in the definitive surgical resection specimen by estimating the proportion of residual tumor in relation to the total tumor area and reported as percentage viability. A pathologic complete response was defined as no viable residual melanoma cells in the surgical specimen. A major pathologic response was defined as <50% viable tumor cells. A minor pathologic response was defined as 50% or greater viable tumor cells, including specimens that had 100% viability at surgery.
measure: Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery
time frame: up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)
description: Recurrence after surgery will be assessed by radiologic scans and confirmed by biopsy. Death within the follow-up period is also considered recurrence. This outcome will report the number of participants who were alive and who had no disease recurrence during the follow-up period.
measure: Overall Survival: Number of Participants Alive One Year After Completing Adjuvant Nivolumab
time frame: up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)
description: Participants were followed for survival for one year after completion of adjuvant nivolumab. Adjuvant nivolumab was planned for up to one year of adjuvant treatment after surgery. This objective reports the number of participants who were alive one year after the completion of adjuvant nivolumab.
measure: Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category
time frame: 12 weeks from baseline to surgery
description: Participants were assessed radiographically and clinically prior to study start and prior to surgery. Lesions were measured, and lesions that were at least 10 mm on CT, MRI, caliper, or ruler, or at least 20 mm on x-ray were documented as Target Lesions. Lesions that did not meet criteria to be Target Lesions were documented as Non-Target lesions. Measurements of Target Lesions were summed. Change in Target Lesion measurements was used to determine response by RECIST 1.1 criteria. Complete Response (CR) indicates a disappearance of all lesions. Partial Response (PR) indicates at least 30% decrease in the sum of Target Lesions. Progressive Disease (PD) indicates at least 20% increase in the sum of Target Lesions, or the appearance of one or more new lesions after baseline. Stable Disease (SD) is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Objective was reported as number of participants within each response category.
measure: Number of Participants With Complete Surgical Resection
time frame: Within 28 days after Day 84
description: Participants' surgical samples were assessed by a pathologist after surgery to determine if complete surgical resection was achieved after neo-adjuvant treatment with nivolumab and HF10. R0 indicates a complete surgical resection was achieved and means no residual tumor was detected after after surgery. R1 means microscopic tumor was detected and a complete surgical resection was not achieved.
measure: Number of Participants With Adverse Events Related to HF10 Treatment
time frame: throughout HF10 treatment (up to 84 days)
description: Participants were monitored for adverse events (AEs) during treatment with HF10 using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to HF10 treatment are grouped by grade 1-2 and grade 3-5 AEs.
measure: Number of Participants With Adverse Events Related to Nivolumab Treatment
time frame: throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery)
description: Participants were monitored for adverse events (AEs) during treatment with nivolumab using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to nivolumab treatment are grouped by grade 1-2 and grade 3-5 AEs.
arm group label: Nivolumab and HF10, all participants
arm group type: Experimental
intervention type: Drug
intervention name: Nivolumab
description: Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.
arm group label: Nivolumab and HF10, all participants
other name: OPDIVO
intervention type: Drug
intervention name: HF10
description: 1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections. All eligible tumors except one will be treated with HF10 up to the maximum volume allowed. The untreated tumor will be used as an untreated control lesion.
arm group label: Nivolumab and HF10, all participants
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Nivolumab
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 