<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/NCT02978625</url>
  </required_header>
  <id_info>
    <org_study_id>NCI-2016-01804</org_study_id>
    <secondary_id>NCI-2016-01804</secondary_id>
    <secondary_id>CINJ #091701</secondary_id>
    <secondary_id>10057</secondary_id>
    <secondary_id>10057</secondary_id>
    <secondary_id>UM1CA186709</secondary_id>
    <secondary_id>UM1CA186716</secondary_id>
    <nct_id>NCT02978625</nct_id>
  </id_info>
  <brief_title>Talimogene Laherparepvec and Nivolumab in Treating Patients With Refractory Lymphomas or Advanced or Refractory Non-melanoma Skin Cancers</brief_title>
  <official_title>A Phase II Study of Talimogene Laherparepvec Followed by Talimogene Laherparepvec + Nivolumab in Refractory T Cell and NK Cell Lymphomas, Cutaneous Squamous Cell Carcinoma, Merkel Cell Carcinoma, and Other Rare Skin Tumors</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Cancer Institute (NCI)</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well talimogene laherparepvec and nivolumab work in treating&#xD;
      patients with lymphomas that do not responded to treatment (refractory) or non-melanoma skin&#xD;
      cancers that have spread to other places in the body (advanced) or do not responded to&#xD;
      treatment. Biological therapies, such as talimogene laherparepvec, use substances made from&#xD;
      living organisms that may stimulate or suppress the immune system in different ways and stop&#xD;
      tumor cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may&#xD;
      help the body's immune system attack the cancer, and may interfere with the ability of tumor&#xD;
      cells to grow and spread. Giving talimogene laherparepvec and nivolumab may work better&#xD;
      compared to usual treatments in treating patients with lymphomas or non-melanoma skin&#xD;
      cancers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVE:&#xD;
&#xD;
      I. To determine the frequency of patients responding (response rate) to talimogene&#xD;
      laherparepvec monotherapy.&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. To determine the local response rate to talimogene laherparepvec in injected tumors.&#xD;
&#xD;
      II. To determine the response rate to talimogene laherparepvec + nivolumab (NIVO).&#xD;
&#xD;
      III. To identify potential pre-treatment and on-treatment correlative biomarkers of local and&#xD;
      systemic immune response.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      Patients receive talimogene laherparepvec intratumorally (IT) and nivolumab intravenously&#xD;
      (IV) over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for&#xD;
      up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo&#xD;
      computed tomography (CT) scan or positron emission tomography (PET)/CT scan on study.&#xD;
      Patients also undergo blood sample collection and biopsies on study.&#xD;
&#xD;
      After completion of study treatment, patients are followed up every 12 weeks for 3 years.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 27, 2017</start_date>
  <completion_date type="Anticipated">June 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 1, 2024</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Response rate to talimogene laherparepvec alone (Part I)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Best overall response rate to talimogene laherparepvec and nivolumab combination therapy (Part II)</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be assessed by RECIST version 1.1.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Durable response rate</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be defined as complete response or partial response lasting &gt;= 6 months.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate by cancer type</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be assessed by RECIST version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate of injected lesions</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be assessed by RECIST version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Response rate of non-injected lesions</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be assessed by RECIST version 1.1.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frequency of curative surgery (unresectable lesion becomes resectable)</measure>
    <time_frame>Up to 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>From start of treatment to time of progression or death, whichever occurs first, assessed at 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>From start of treatment to time of progression or death, whichever occurs first, assessed at 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 1 year</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival</measure>
    <time_frame>At 2 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of adverse events</measure>
    <time_frame>Up to week 24</time_frame>
    <description>Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Change in herpes simplex virus (HSV) serostatus assessed in blood specimens</measure>
    <time_frame>Baseline to week 6</time_frame>
    <description>Will be analyzed using descriptive statistics. A test of proportions will be performed.</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker analysis of %PD-L1, flow cytometry for HVEM, NECTIN1/2, and IDO, tryptophan and L-kynurenine, cytokine levels, Nanostring, number of non-synonymous mutations, and % T-cell receptor (TCR) clonality</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be analyzed using descriptive statistics. Logistic regression of response rate on the variable will be performed.</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker analysis of necrosis and Nanostring</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be analyzed using descriptive statistics. Logistic regression of response rate on the variable will be performed.</description>
  </other_outcome>
  <other_outcome>
    <measure>Biomarker analysis of herpes simplex virus (HSV) status, Merkel cell polyomavirus status, and PD-L1 status</measure>
    <time_frame>Up to 1 year</time_frame>
    <description>Will be analyzed using descriptive statistics. Test of proportions and logistic regression will be performed.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">68</enrollment>
  <condition>Adenoid Cystic Skin Carcinoma</condition>
  <condition>Adnexal Carcinoma</condition>
  <condition>Anaplastic Large Cell Lymphoma, ALK-Negative</condition>
  <condition>Anaplastic Large Cell Lymphoma, ALK-Positive</condition>
  <condition>Apocrine Carcinoma</condition>
  <condition>Cylindrocarcinoma</condition>
  <condition>Digital Papillary Adenocarcinoma</condition>
  <condition>Endocrine Mucin-Producing Sweat Gland Carcinoma</condition>
  <condition>Extramammary Paget Disease</condition>
  <condition>Extraocular Cutaneous Sebaceous Carcinoma</condition>
  <condition>Hidradenocarcinoma</condition>
  <condition>Keratoacanthoma</condition>
  <condition>Malignant Sweat Gland Neoplasm</condition>
  <condition>Merkel Cell Carcinoma</condition>
  <condition>Microcystic Adnexal Carcinoma</condition>
  <condition>NK-Cell Lymphoma, Unclassifiable</condition>
  <condition>Papillary Adenocarcinoma</condition>
  <condition>Porocarcinoma</condition>
  <condition>Primary Cutaneous Mucinous Carcinoma</condition>
  <condition>Recurrent Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Recurrent T-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Anaplastic Large Cell Lymphoma</condition>
  <condition>Refractory Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Merkel Cell Carcinoma</condition>
  <condition>Refractory Mycosis Fungoides</condition>
  <condition>Refractory Primary Cutaneous T-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Refractory Skin Squamous Cell Carcinoma</condition>
  <condition>Refractory T-Cell Non-Hodgkin Lymphoma</condition>
  <condition>Sezary Syndrome</condition>
  <condition>Signet Ring Cell Carcinoma</condition>
  <condition>Skin Basal Cell Carcinoma</condition>
  <condition>Skin Basosquamous Cell Carcinoma</condition>
  <condition>Skin Squamous Cell Carcinoma</condition>
  <condition>Spiradenocarcinoma</condition>
  <condition>Squamoid Eccrine Ductal Carcinoma</condition>
  <condition>Squamous Cell Carcinoma of Unknown Primary</condition>
  <condition>Sweat Gland Carcinoma</condition>
  <condition>Trichilemmal Carcinoma</condition>
  <condition>Vulvar Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients receive talimogene laherparepvec IT and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo, CT scan or PET/CT on study. Patients also undergo blood sample collection and biopsies on study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biopsy</intervention_name>
    <description>Undergo tissue biopsy</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
    <other_name>BIOPSY_TYPE</other_name>
    <other_name>Bx</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Biospecimen Collection</intervention_name>
    <description>Undergo blood sample collection</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
    <other_name>Biological Sample Collection</other_name>
    <other_name>Biospecimen Collected</other_name>
    <other_name>Specimen Collection</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Computed Tomography</intervention_name>
    <description>Undergo CT</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
    <other_name>CAT</other_name>
    <other_name>CAT Scan</other_name>
    <other_name>Computed Axial Tomography</other_name>
    <other_name>Computerized Axial Tomography</other_name>
    <other_name>Computerized axial tomography (procedure)</other_name>
    <other_name>Computerized Tomography</other_name>
    <other_name>CT</other_name>
    <other_name>CT Scan</other_name>
    <other_name>tomography</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Laboratory Biomarker Analysis</intervention_name>
    <description>Correlative studies</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
    <other_name>ABP 206</other_name>
    <other_name>BMS-936558</other_name>
    <other_name>CMAB819</other_name>
    <other_name>MDX-1106</other_name>
    <other_name>NIVO</other_name>
    <other_name>Nivolumab Biosimilar ABP 206</other_name>
    <other_name>Nivolumab Biosimilar CMAB819</other_name>
    <other_name>ONO-4538</other_name>
    <other_name>Opdivo</other_name>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Positron Emission Mammography</intervention_name>
    <description>Undergo PET/CT</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Talimogene Laherparepvec</intervention_name>
    <description>Given IT</description>
    <arm_group_label>Treatment (talimogene laherparepvec, nivolumab)</arm_group_label>
    <other_name>ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene</other_name>
    <other_name>Imlygic</other_name>
    <other_name>JS1 34.5-hGMCSF 47- pA-</other_name>
    <other_name>T-VEC</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must have histologic or cytologic diagnosis of non-melanoma skin cancer&#xD;
             (NMSC) or lymphomas other than B-cell lymphomas; as both of those terms are categories&#xD;
             rather than specific diagnoses, specific guidance on eligible tumor types is provided&#xD;
             below&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Included tumor types&#xD;
&#xD;
               -  T cell and NK cell lymphomas, including, but not limited to: cutaneous T-cell&#xD;
                  lymphomas (CTCL), mycosis fungoides (MF), Sezary syndrome (SS), peripheral T-cell&#xD;
                  lymphoma (PTCL), ALK-positive and ALK-negative anaplastic large cell lymphoma&#xD;
                  (ALCL), and NK-cell lymphomas&#xD;
&#xD;
               -  Merkel cell carcinoma&#xD;
&#xD;
               -  Squamous cell carcinoma of the skin, including keratoacanthomas, vulvar squamous&#xD;
                  carcinoma, and mixed histology tumors, such as basosquamous carcinoma, and&#xD;
                  squamous cell carcinoma of unknown primary consistent with skin origin&#xD;
&#xD;
               -  Other non-melanoma skin cancers&#xD;
&#xD;
                    -  Basal cell carcinoma&#xD;
&#xD;
                    -  Malignant sweat gland tumors, including porocarcinoma, hidradenocarcinoma,&#xD;
                       spiradenocarcinoma, cylindrocarcinoma, microcystic adnexal carcinoma and&#xD;
                       related entities, squamoid eccrine ductal carcinoma, cutaneous adenoid&#xD;
                       cystic carcinoma, digital papillary adenocarcinoma, primary cutaneous&#xD;
                       mucinous carcinoma, endocrine mucin-producing sweat gland carcinoma, primary&#xD;
                       cutaneous signet ring cell carcinoma, cutaneous apocrine gland carcinoma,&#xD;
                       and extraocular sebaceous carcinoma&#xD;
&#xD;
                    -  Adnexal carcinoma&#xD;
&#xD;
                    -  Trichilemmal carcinoma&#xD;
&#xD;
                    -  Extramammary Paget's disease&#xD;
&#xD;
                    -  Any other rare tumor of the skin with approval of principle investigator&#xD;
                       (PI)&#xD;
&#xD;
          -  PART II (after February 2020 amendment):&#xD;
&#xD;
               -  The Merkel cell carcinoma (MCC)-2 cohort will include patients with MCC&#xD;
&#xD;
               -  The squamous cell carcinoma (SCC)-2 cohort will include patients with SCC&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Patients with T cell and natural killer (NK)&#xD;
             cell lymphomas must be refractory to, be intolerant of, have relapsed following, or&#xD;
             have refused all standard life-prolonging therapies&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Patients with non-melanoma skin cancers&#xD;
             (NMSC) must have advanced or refractory tumors&#xD;
&#xD;
               -  Advanced/unresectable is defined by at least 1 of the following criteria: tumors&#xD;
                  2 cm or more, tumors considered unresectable, tumors invading deep tissues such&#xD;
                  as muscle, cartilage or bone, tumors showing perineural invasion, and/or tumors&#xD;
                  metastatic to loco-regional lymph nodes and/or distant sites&#xD;
&#xD;
               -  Refractory is defined by persistent or recurrent tumor despite prior therapy&#xD;
                  consisting of at least 1 of the following: surgery, radiation therapy,&#xD;
                  intralesional therapy, topical therapy, or systemic therapy&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Subjects must have at least 1 cutaneous,&#xD;
             subcutaneous, or nodal lesion that is suitable for intralesional injection, with or&#xD;
             without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc)&#xD;
             are not eligible for injection because the area cannot be properly contained with an&#xD;
             occlusive dressing&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Subjects must have radiographically or&#xD;
             clinically measurable disease, defined as at least one lesion that is &gt;= 10 mm in&#xD;
             diameter in at least 1 dimension, or an aggregate of lesions that measures &gt;= 10 mm in&#xD;
             diameter in at least 1 dimension&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Subjects must be able and willing to undergo&#xD;
             serial biopsies of injected lesion(s) and, when applicable and clinically feasible,&#xD;
             non-injected lesions&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Eastern Cooperative Oncology Group (ECOG)&#xD;
             performance status =&lt; 2 (Karnofsky &gt;= 60%)&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Absolute neutrophil count (ANC) &gt;= 1.2 x&#xD;
             10^9/L&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Hemoglobin &gt;= 9 g/dL without transfusion in&#xD;
             the preceding 7 days&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Platelets &gt;= 75 x 10^9/L&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Serum total bilirubin =&lt; 1.5 x institutional&#xD;
             upper limit of normal (ULN) (patients with Gilbert's syndrome with a total bilirubin &lt;&#xD;
             3.0 mg/dL)&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Aspartate aminotransferase (AST) and alanine&#xD;
             aminotransferase (ALT) =&lt; 2.5 x institutional ULN&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Serum creatinine =&lt; 1.5 mg/dL OR calculated&#xD;
             creatinine clearance (Cockcroft-Gault formula) &gt;= 50 mL/min OR 24-hour urine&#xD;
             creatinine clearance &gt;= 50 mL/min&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Prothrombin time (PT)/international&#xD;
             normalized ratio (INR) and partial thromboplastin time (PTT) =&lt; 1.5 x institutional&#xD;
             ULN, unless the subject is on anticoagulant therapy; (if the subject is receiving&#xD;
             anticoagulant therapy, PT, and activated PTT [aPTT] must be within therapeutic range&#xD;
             of intended use of anticoagulants)&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Talimogene laherparepvec, nivolumab and other&#xD;
             therapeutic agents used in this trial may cause fetal harm when administered to a&#xD;
             pregnant woman; women of child-bearing potential (WOCBP) and must agree to use&#xD;
             adequate contraception (hormonal or barrier method of birth control; abstinence from&#xD;
             heterosexual intercourse) prior to study entry, during the study participation, and&#xD;
             for 7 months after the last dose of the drug; WOCBP must have a negative serum&#xD;
             pregnancy test within 14 days prior to randomization; should a woman become pregnant&#xD;
             or suspect she is pregnant while she or her partner is participating in this study,&#xD;
             she should inform her treating physician immediately; men must agree to use adequate&#xD;
             contraception prior to study entry, during the study participation and for 7 months&#xD;
             after the last dose of the drug&#xD;
&#xD;
          -  PART I (before February 2020 amendment): Ability to understand and the willingness to&#xD;
             sign a written informed consent document&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Subjects in expansion cohorts MCC-2 and SCC-2&#xD;
             must have a diagnosis of MCC or SCC, respectively&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Subjects must have refractory disease,&#xD;
             defined as evidence of progressive disease despite prior therapy with a PD-1 or PD-L1&#xD;
             blocking antibody (avelumab, pembrolizumab, nivolumab, cemiplimab, etc.); progression&#xD;
             must have occurred during PD-1 or PD-L1 directed therapy or within 6 months of the&#xD;
             last dose of PD-1 or PD-L1 directed therapy&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Subjects must have at least 1 cutaneous,&#xD;
             subcutaneous, or nodal lesion that is suitable for intralesional injection, with or&#xD;
             without the use of ultrasound; lesions in mucosal surfaces (periocular, nasal, etc)&#xD;
             are not eligible for injection because the area cannot be properly contained with an&#xD;
             occlusive dressing&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Subjects must have radiographically or&#xD;
             clinically measurable disease, defined as at least one lesion that is &gt;= 10 mm in&#xD;
             diameter in at least 1 dimension, or an aggregate of lesions that measures &gt;= 10 mm in&#xD;
             diameter in at least 1 dimension&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Subjects must be able and willing to undergo&#xD;
             serial biopsies of injected lesion(s) and, when applicable and clinically feasible,&#xD;
             non-injected lesions&#xD;
&#xD;
          -  PART II (after February 2020 amendment): ECOG performance status =&lt; 2 (Karnofsky &gt;=&#xD;
             60%)&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Absolute neutrophil count (ANC) &gt;= 1.2 x&#xD;
             10^9/L&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Hemoglobin &gt;= 9 g/dL without transfusion in&#xD;
             the preceding 7 days&#xD;
&#xD;
          -  PART II: P (after February 2020 amendment): Platelets &gt;= 75 x 10^9/L&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Serum total bilirubin =&lt; 1.5 x institutional&#xD;
             upper limit of normal (ULN) (Patients with Gilbert's Syndrome with a total bilirubin &lt;&#xD;
             3.0 mg/dL.)&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Aspartate aminotransferase (AST) and alanine&#xD;
             aminotransferase (ALT) =&lt; 2.5 x institutional ULN&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Serum creatinine =&lt; 1.5 mg/dL OR calculated&#xD;
             creatinine clearance (Cockcroft-Gault formula) &gt;= 50 mL/min OR 24-hour urine&#xD;
             creatinine clearance &gt;= 50 mL/min&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Prothrombin time (PT)/international&#xD;
             normalized ratio (INR) and partial thromboplastin time (PTT) =&lt; 1.5 x institutional&#xD;
             ULN, unless the subject is on anticoagulant therapy; (if the subject is receiving&#xD;
             anticoagulant therapy, PT, and aPTT must be within therapeutic range of intended use&#xD;
             of anticoagulants)&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Talimogene laherparepvec, nivolumab and other&#xD;
             therapeutic agents used in this trial may cause fetal harm when administered to a&#xD;
             pregnant woman; women of child-bearing potential (WOCBP) and must agree to use&#xD;
             adequate contraception (hormonal or barrier method of birth control; abstinence from&#xD;
             heterosexual intercourse) prior to study entry, during the study participation, and&#xD;
             for 7 months after the last dose of the drug; WOCBP must have a negative serum&#xD;
             pregnancy test within 14 days prior to randomization; should a woman become pregnant&#xD;
             or suspect she is pregnant while she or her partner is participating in this study,&#xD;
             she should inform her treating physician immediately; men must agree to use adequate&#xD;
             contraception prior to study entry, during the study participation and for 7 months&#xD;
             after the last dose of the drug&#xD;
&#xD;
          -  PART II (after February 2020 amendment): Ability to understand and the willingness to&#xD;
             sign a written informed consent document&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Excluded tumor types&#xD;
&#xD;
               -  Melanoma&#xD;
&#xD;
               -  Bone sarcomas&#xD;
&#xD;
               -  Soft tissue sarcomas, including angiosarcoma, primary cutaneous leiomyosarcoma,&#xD;
                  dermatofibrosarcoma protuberans&#xD;
&#xD;
               -  Leukemias&#xD;
&#xD;
               -  Myeloid sarcoma, leukemia cutis, and chloroma&#xD;
&#xD;
               -  Hodgkin's lymphoma&#xD;
&#xD;
               -  B cell lymphoma&#xD;
&#xD;
          -  Patients who have had systemic therapy or radiotherapy within 3 weeks prior to the&#xD;
             first dose of study therapy&#xD;
&#xD;
          -  Untreated central nervous system (CNS) involvement; patients with known brain&#xD;
             metastases are eligible if they have been treated and are stable in the view of the&#xD;
             treating investigator&#xD;
&#xD;
          -  Previous treatment with talimogene laherparepvec or other herpes virus based therapy;&#xD;
             (prior therapy with checkpoint inhibitors and/or other immunotherapy is allowed)&#xD;
&#xD;
          -  Patients who have not recovered from adverse events due to prior anti-cancer therapy&#xD;
             (i.e., have residual toxicities &gt; grade 1 excepting alopecia, peripheral sensory&#xD;
             neuropathy, and stable endocrine insufficiencies such as thyroid and adrenal&#xD;
             insufficiency)&#xD;
&#xD;
          -  Second primary malignancy, only if it would affect the safety of the treatment or the&#xD;
             subject's ability to complete study-related procedures&#xD;
&#xD;
          -  History or evidence of active autoimmune disease (e.g., pneumonitis,&#xD;
             glomerulonephritis, vasculitis, or other); or history of active autoimmune disease&#xD;
             that has required systemic treatment (i.e., use of corticosteroids, immunosuppressive&#xD;
             drugs or biological agents used for treatment of autoimmune diseases) within 2 months&#xD;
             of enrollment; (replacement therapy [e.g., thyroxine for hypothyroidism, insulin for&#xD;
             diabetes or physiologic corticosteroid replacement therapy for adrenal or pituitary&#xD;
             insufficiency] is not considered a form of systemic treatment for autoimmune disease)&#xD;
&#xD;
          -  Evidence of clinically significant immunosuppression such as the following:&#xD;
&#xD;
               -  Primary immunodeficiency state such as severe combined immunodeficiency disease&#xD;
&#xD;
               -  Receiving systemic immunosuppressive therapy including prednisone &gt; 10 mg per day&#xD;
                  (or equivalent), tacrolimus, everolimus, sirolimus, mycophenolate mofetil,&#xD;
                  etanercept, infliximab, etc.&#xD;
&#xD;
               -  Recipients of solid organ, bone marrow, or stem cell transplants; auto transplant&#xD;
                  recipients are allowed&#xD;
&#xD;
               -  Notes: Oral steroid doses =&lt; 10 mg/day of prednisone (or equivalent) are not&#xD;
                  considered immunosuppressive and are permitted; inhaled and intraarticular&#xD;
                  corticosteroids are permitted&#xD;
&#xD;
          -  Active herpetic skin lesions or prior complications of herpetic infection (e.g.,&#xD;
             herpetic keratitis or encephalitis)&#xD;
&#xD;
          -  Viral infections requiring intermittent or chronic systemic (intravenous or oral)&#xD;
             treatment with an antiherpetic drug (e.g., acyclovir), other than intermittent topical&#xD;
             use&#xD;
&#xD;
          -  Other viral infections:&#xD;
&#xD;
               -  Known to have acute or chronic active hepatitis B or hepatitis C infection&#xD;
&#xD;
               -  Known to have human immunodeficiency virus (HIV) infection&#xD;
&#xD;
               -  Prior therapy with viral-based tumor vaccine&#xD;
&#xD;
               -  Received live vaccine within 28 days prior to enrollment&#xD;
&#xD;
          -  Subject who is unwilling to minimize exposure with his/her blood or other body fluids&#xD;
             to individuals who are at higher risks for human herpesvirus 1 (HSV-1) induced&#xD;
             complications such as immunosuppressed individuals, individuals known to have HIV&#xD;
             infection, pregnant women, or children under the age of 1 year, during talimogene&#xD;
             laherparepvec treatment and through 30 days after the last dose of talimogene&#xD;
             laherparepvec&#xD;
&#xD;
          -  Has a history of (non-infectious) pneumonitis that required steroids or current&#xD;
             pneumonitis&#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&#xD;
&#xD;
          -  Female subject is pregnant or breast-feeding, or planning to become pregnant during&#xD;
             study treatment and through 7 months after the last dose of treatment; female subject&#xD;
             of childbearing potential who is unwilling to use acceptable method(s) of effective&#xD;
             contraception during study treatment and through 7 months after the last dose of&#xD;
             treatment; sexually active subjects and their partners unwilling to use male or female&#xD;
             latex condom to avoid potential viral transmission during sexual contact while on&#xD;
             treatment and within 30 days after treatment with talimogene laherparepvec&#xD;
&#xD;
          -  Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to&#xD;
             talimogene laherparepvec or any of its components or nivolumab, or history of severe&#xD;
             hypersensitivity reaction to any monoclonal antibody&#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>Ann (Annie) W Silk</last_name>
    <role>Principal Investigator</role>
    <affiliation>Dana-Farber - Harvard Cancer Center LAO</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Los Angeles County-USC Medical Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>USC / Norris Comprehensive Cancer Center</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UC Irvine Health/Chao Family Comprehensive Cancer Center</name>
      <address>
        <city>Orange</city>
        <state>California</state>
        <zip>92868</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Keck Medical Center of USC Pasadena</name>
      <address>
        <city>Pasadena</city>
        <state>California</state>
        <zip>91105</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California Davis Comprehensive Cancer Center</name>
      <address>
        <city>Sacramento</city>
        <state>California</state>
        <zip>95817</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UCHealth University of Colorado Hospital</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Aventura</name>
      <address>
        <city>Aventura</city>
        <state>Florida</state>
        <zip>33180</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Coral Gables</name>
      <address>
        <city>Coral Gables</city>
        <state>Florida</state>
        <zip>33146</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Deerfield Beach</name>
      <address>
        <city>Deerfield Beach</city>
        <state>Florida</state>
        <zip>33442</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Miami Miller School of Medicine-Sylvester Cancer Center</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Kendall</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33176</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UM Sylvester Comprehensive Cancer Center at Plantation</name>
      <address>
        <city>Plantation</city>
        <state>Florida</state>
        <zip>33324</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Northwestern University</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Clinical Research Center</name>
      <address>
        <city>Fairway</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center-Overland Park</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital-Indian Creek Campus</name>
      <address>
        <city>Overland Park</city>
        <state>Kansas</state>
        <zip>66211</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Hospital-Westwood Cancer Center</name>
      <address>
        <city>Westwood</city>
        <state>Kansas</state>
        <zip>66205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins University/Sidney Kimmel Cancer Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital Cancer Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center at West County Hospital</name>
      <address>
        <city>Creve Coeur</city>
        <state>Missouri</state>
        <zip>63141</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center - North</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64154</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center - Lee's Summit</name>
      <address>
        <city>Lee's Summit</city>
        <state>Missouri</state>
        <zip>64064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Cancer Center at North Kansas City Hospital</name>
      <address>
        <city>North Kansas City</city>
        <state>Missouri</state>
        <zip>64116</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center-South County</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Siteman Cancer Center at Saint Peters Hospital</name>
      <address>
        <city>Saint Peters</city>
        <state>Missouri</state>
        <zip>63376</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Nebraska Medical Center</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68198</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center</name>
      <address>
        <city>Lebanon</city>
        <state>New Hampshire</state>
        <zip>03756</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rutgers Cancer Institute of New Jersey</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Roswell Park Cancer Institute</name>
      <address>
        <city>Buffalo</city>
        <state>New York</state>
        <zip>14263</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Laura and Isaac Perlmutter Cancer Center at NYU Langone</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UNC Lineberger Comprehensive Cancer Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Cancer Institute (UPCI)</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntsman Cancer Institute/University of Utah</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>July 2023</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>November 30, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 1, 2016</study_first_posted>
  <last_update_submitted>September 12, 2023</last_update_submitted>
  <last_update_submitted_qc>September 12, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycoses</mesh_term>
    <mesh_term>Carcinoma, Merkel Cell</mesh_term>
    <mesh_term>Lymphoma</mesh_term>
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Adenocarcinoma</mesh_term>
    <mesh_term>Lymphoma, Non-Hodgkin</mesh_term>
    <mesh_term>Mycosis Fungoides</mesh_term>
    <mesh_term>Carcinoma, Basal Cell</mesh_term>
    <mesh_term>Sezary Syndrome</mesh_term>
    <mesh_term>Lymphoma, T-Cell</mesh_term>
    <mesh_term>Lymphoma, T-Cell, Cutaneous</mesh_term>
    <mesh_term>Lymphoma, Large-Cell, Anaplastic</mesh_term>
    <mesh_term>Carcinoma, Ductal</mesh_term>
    <mesh_term>Paget Disease, Extramammary</mesh_term>
    <mesh_term>Adenocarcinoma, Papillary</mesh_term>
    <mesh_term>Carcinoma, Signet Ring Cell</mesh_term>
    <mesh_term>Carcinoma, Skin Appendage</mesh_term>
    <mesh_term>Adenocarcinoma, Mucinous</mesh_term>
    <mesh_term>Adenocarcinoma, Sebaceous</mesh_term>
    <mesh_term>Sweat Gland Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Basosquamous</mesh_term>
    <mesh_term>Keratoacanthoma</mesh_term>
    <mesh_term>Recurrence</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Talimogene laherparepvec</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02978625
org study id: NCI-2016-01804
secondary id: NCI-2016-01804
secondary id: CINJ #091701
secondary id: 10057
secondary id: 10057
secondary id: UM1CA186709
secondary id: UM1CA186716
nct id: NCT02978625
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This phase II trial studies how well talimogene laherparepvec and nivolumab work in treating
      patients with lymphomas that do not responded to treatment (refractory) or non-melanoma skin
      cancers that have spread to other places in the body (advanced) or do not responded to
      treatment. Biological therapies, such as talimogene laherparepvec, use substances made from
      living organisms that may stimulate or suppress the immune system in different ways and stop
      tumor cells from growing. Immunotherapy with monoclonal antibodies, such as nivolumab, may
      help the body's immune system attack the cancer, and may interfere with the ability of tumor
      cells to grow and spread. Giving talimogene laherparepvec and nivolumab may work better
      compared to usual treatments in treating patients with lymphomas or non-melanoma skin
      cancers.
PRIMARY OBJECTIVE:

      I. To determine the frequency of patients responding (response rate) to talimogene
      laherparepvec monotherapy.

      SECONDARY OBJECTIVES:

      I. To determine the local response rate to talimogene laherparepvec in injected tumors.

      II. To determine the response rate to talimogene laherparepvec + nivolumab (NIVO).

      III. To identify potential pre-treatment and on-treatment correlative biomarkers of local and
      systemic immune response.

      OUTLINE:

      Patients receive talimogene laherparepvec intratumorally (IT) and nivolumab intravenously
      (IV) over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for
      up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo
      computed tomography (CT) scan or positron emission tomography (PET)/CT scan on study.
      Patients also undergo blood sample collection and biopsies on study.

      After completion of study treatment, patients are followed up every 12 weeks for 3 years.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Response rate to talimogene laherparepvec alone (Part I)
time frame: Up to 1 year
description: Will be assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
measure: Best overall response rate to talimogene laherparepvec and nivolumab combination therapy (Part II)
time frame: Up to 1 year
description: Will be assessed by RECIST version 1.1.
measure: Durable response rate
time frame: Up to 1 year
description: Will be defined as complete response or partial response lasting >= 6 months.
measure: Response rate by cancer type
time frame: Up to 1 year
description: Will be assessed by RECIST version 1.1.
measure: Response rate of injected lesions
time frame: Up to 1 year
description: Will be assessed by RECIST version 1.1.
measure: Response rate of non-injected lesions
time frame: Up to 1 year
description: Will be assessed by RECIST version 1.1.
measure: Frequency of curative surgery (unresectable lesion becomes resectable)
time frame: Up to 1 year
measure: Progression free survival
time frame: From start of treatment to time of progression or death, whichever occurs first, assessed at 1 year
measure: Progression free survival
time frame: From start of treatment to time of progression or death, whichever occurs first, assessed at 2 years
measure: Overall survival
time frame: At 1 year
measure: Overall survival
time frame: At 2 years
measure: Incidence of adverse events
time frame: Up to week 24
description: Will be assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
measure: Change in herpes simplex virus (HSV) serostatus assessed in blood specimens
time frame: Baseline to week 6
description: Will be analyzed using descriptive statistics. A test of proportions will be performed.
measure: Biomarker analysis of %PD-L1, flow cytometry for HVEM, NECTIN1/2, and IDO, tryptophan and L-kynurenine, cytokine levels, Nanostring, number of non-synonymous mutations, and % T-cell receptor (TCR) clonality
time frame: Up to 1 year
description: Will be analyzed using descriptive statistics. Logistic regression of response rate on the variable will be performed.
measure: Biomarker analysis of necrosis and Nanostring
time frame: Up to 1 year
description: Will be analyzed using descriptive statistics. Logistic regression of response rate on the variable will be performed.
measure: Biomarker analysis of herpes simplex virus (HSV) status, Merkel cell polyomavirus status, and PD-L1 status
time frame: Up to 1 year
description: Will be analyzed using descriptive statistics. Test of proportions and logistic regression will be performed.
arm group label: Treatment (talimogene laherparepvec, nivolumab)
arm group type: Experimental
description: Patients receive talimogene laherparepvec IT and nivolumab IV over 30 minutes on day 1. Cycles repeat every 21 days for cycle 1 then every 14 days for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients undergo, CT scan or PET/CT on study. Patients also undergo blood sample collection and biopsies on study.
intervention type: Procedure
intervention name: Biopsy
description: Undergo tissue biopsy
arm group label: Treatment (talimogene laherparepvec, nivolumab)
other name: BIOPSY_TYPE
other name: Bx
intervention type: Procedure
intervention name: Biospecimen Collection
description: Undergo blood sample collection
arm group label: Treatment (talimogene laherparepvec, nivolumab)
other name: Biological Sample Collection
other name: Biospecimen Collected
other name: Specimen Collection
intervention type: Procedure
intervention name: Computed Tomography
description: Undergo CT
arm group label: Treatment (talimogene laherparepvec, nivolumab)
other name: CAT
other name: CAT Scan
other name: Computed Axial Tomography
other name: Computerized Axial Tomography
other name: Computerized axial tomography (procedure)
other name: Computerized Tomography
other name: CT
other name: CT Scan
other name: tomography
intervention type: Other
intervention name: Laboratory Biomarker Analysis
description: Correlative studies
arm group label: Treatment (talimogene laherparepvec, nivolumab)
intervention type: Biological
intervention name: Nivolumab
description: Given IV
arm group label: Treatment (talimogene laherparepvec, nivolumab)
other name: ABP 206
other name: BMS-936558
other name: CMAB819
other name: MDX-1106
other name: NIVO
other name: Nivolumab Biosimilar ABP 206
other name: Nivolumab Biosimilar CMAB819
other name: ONO-4538
other name: Opdivo
intervention type: Procedure
intervention name: Positron Emission Mammography
description: Undergo PET/CT
arm group label: Treatment (talimogene laherparepvec, nivolumab)
intervention type: Biological
intervention name: Talimogene Laherparepvec
description: Given IT
arm group label: Treatment (talimogene laherparepvec, nivolumab)
other name: ICP34.5-, ICP47-deleted Herpes Simplex Virus 1 (HSV-1) Incorporating the Human GM-CSF Gene
other name: Imlygic
other name: JS1 34.5-hGMCSF 47- pA-
other name: T-VEC
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ann (Annie) W Silk
role: Principal Investigator
affiliation: Dana-Farber - Harvard Cancer Center LAO
facility: 
facility: 
facility: 
facility: 
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country: United States
responsible party type: Sponsor
mesh term: Mycoses
mesh term: Carcinoma, Merkel Cell
mesh term: Lymphoma
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Adenocarcinoma
mesh term: Lymphoma, Non-Hodgkin
mesh term: Mycosis Fungoides
mesh term: Carcinoma, Basal Cell
mesh term: Sezary Syndrome
mesh term: Lymphoma, T-Cell
mesh term: Lymphoma, T-Cell, Cutaneous
mesh term: Lymphoma, Large-Cell, Anaplastic
mesh term: Carcinoma, Ductal
mesh term: Paget Disease, Extramammary
mesh term: Adenocarcinoma, Papillary
mesh term: Carcinoma, Signet Ring Cell
mesh term: Carcinoma, Skin Appendage
mesh term: Adenocarcinoma, Mucinous
mesh term: Adenocarcinoma, Sebaceous
mesh term: Sweat Gland Neoplasms
mesh term: Carcinoma, Basosquamous
mesh term: Keratoacanthoma
mesh term: Recurrence
mesh term: Nivolumab
mesh term: Talimogene laherparepvec