<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/NCT03823131</url>
  </required_header>
  <id_info>
    <org_study_id>172021</org_study_id>
    <secondary_id>NCI-2018-02901</secondary_id>
    <nct_id>NCT03823131</nct_id>
  </id_info>
  <brief_title>Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat</brief_title>
  <official_title>The Trifecta Study: Optimizing Antitumor Immunity Using Plasmid Electroporation, Pembrolizumab, and Epacadostat</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chase Heaton, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Incyte Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>OncoSec Medical Incorporated</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This phase II trial studies how well tavokinogene telseplasmid with electroporation&#xD;
      (tavo-EP), pembrolizumab, and epacadostat work in treating patients with squamous cell&#xD;
      carcinoma of the head and neck that cannot be removed by surgery. Tavokinogene telseplasmid&#xD;
      with electroporation is a gene therapy that may delay of tumor growth and which may have less&#xD;
      toxicity than other methods of gene delivery. Immunotherapy with monoclonal antibodies, such&#xD;
      as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with&#xD;
      the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells&#xD;
      by blocking some of the enzymes needed for cell growth. Giving tavokinogene telseplasmid with&#xD;
      electroporation, pembrolizumab, and epacadostat may work better in treating squamous cell&#xD;
      carcinoma of the head and neck.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      PRIMARY OBJECTIVES:&#xD;
&#xD;
      I. Dose Escalation Safety Lead-Ins: Assess the safety of tavo-EP and pembrolizumab in&#xD;
      combination with epacadostat (CTCAE version 4).&#xD;
&#xD;
      II. Dose Expansion: Determine whether the combination therapy in each arm increases the best&#xD;
      overall response rate (BORR) compared with historical data for pembrolizumab monotherapy&#xD;
&#xD;
      SECONDARY OBJECTIVES:&#xD;
&#xD;
      I. Dose Expansion: Determine the durability of clinical benefits in participants treated with&#xD;
      combination therapy in each arm, as assessed by time to progression, median progression-free&#xD;
      survival (PFS), median overall survival (OS).&#xD;
&#xD;
      EXPLORATORY OBJECTIVES:&#xD;
&#xD;
      I. Determine the effects of combination therapy on treated and untreated lesions by examining&#xD;
      paired biopsy specimens for changes in inflammatory gene expression, relative proportion of&#xD;
      effector versus regulatory T cells, evaluation of inflammatory cytokines, T-cell activation,&#xD;
      clonality, and other hallmarks of immune activation.&#xD;
&#xD;
      II. Explore systemic markers of immune activation by examining circulating T-cell populations&#xD;
      for changes in the frequency and effector function of short-lived effector cells and memory T&#xD;
      cells.&#xD;
&#xD;
      III. Explore changes in functional immune responses using Elispot and other assays.&#xD;
&#xD;
      IV. To explore biomarkers that inform scientific understanding of this therapeutic treatment&#xD;
      through analysis of specimens retained for Future Biomedical Research.&#xD;
&#xD;
      OUTLINE:&#xD;
&#xD;
      This is a multi-center, open label, 2-stage, double-arm, clinical trial in which participants&#xD;
      in Stage 1 will receive either tavo-EP with pembrolizumab, and epacadostat (Arm A), tavo-EP&#xD;
      and pembrolizumab (Arm B), or CORVax, tavo-EP and pembrolizumab (Arm C). Arms B and C will&#xD;
      only open to enrollment if the treatment is determined to be effective in Arm A.&#xD;
&#xD;
      Participants will be followed at 3-month intervals for toxicity and radiographic imaging (1)&#xD;
      until start of a new anti-cancer treatment, (2) until 30 days after documented disease&#xD;
      progression, (3) until death, or (4) until 36 months from the initiation of treatment on&#xD;
      study, whichever comes first. Each subject will be followed for overall survival until death,&#xD;
      withdrawal of consent, or at the time of study closure, whichever occurs first.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Treatment Ineffective&#xD;
  </why_stopped>
  <start_date type="Actual">May 2, 2019</start_date>
  <completion_date type="Actual">July 31, 2022</completion_date>
  <primary_completion_date type="Actual">July 31, 2022</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Best Overall Response Rate</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Months of Progression-Free Survival (PFS)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Progression-free survival will be calculated as number of months from the first dosing date until the date of disease progression (i.e the date of the tumor imaging following baseline per central imaging assessment by a radiologist) or death from any cause. Per RECIST version 1.1, Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants who do not have documented disease progression will have their months of PFS censored on the last date of tumor assessment, or death, whichever comes first. Censoring data on date of last tumor imaging to calculate the median PFS will not occur until the overall survival data collection for all participants has been completed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Overall Survival (OS)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Overall survival (OS) is defined as the number of months from the date of enrollment until the date of death regardless of cause, last date of follow-up, or date of study closure (if still alive), whichever comes first. Median months of overall participant survival will be reported using descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Time to Response</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Time to response is defined as the number of days from the date of enrollment to the date of the first documented response of CR or PR. The median time to response will be summarized by descriptive statistics.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>The disease control rate is defined as the best response recorded from the start of treatment including stable disease, until disease progression/recurrence (PD). Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The proportion of participants relative to the total size of the All Treated Subjects population having a demonstrated response of CR, PR, or SD, with a confirmatory scan will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Benefit Rate (CBR)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Clinical benefit rate (CBR) is defined as the percentage of participants who achieved a best overall response of CR, PR and SD with a duration of response lasting at least 6 months or longer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Duration of Response</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>The duration of response (DOR) will be calculated for participants who achieved a best overall response of CR or PR and calculated as the number of days from the date when CR or PR is first confirmed to the date of progression or death. Participants who do not have a documented progression or death will be censored on the last date of tumor assessment. The median DOR and 95% confidence intervals will be reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of Participants With Reported Treatment-related Adverse Events (AEs)</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>The proportion of participants with reported treatment-related adverse events, which are adverse events defined as having an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 will be reported.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">14</enrollment>
  <condition>Metastatic Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Recurrent Head and Neck Squamous Cell Carcinoma</condition>
  <condition>Unresectable Head and Neck Squamous Cell Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm A: Tavo-EP, pembrolizumab, epacadostat</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm B: Tavo-EP, pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm C: Tavo-EP, pembrolizumab, CORVax</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ImmunoPulse</intervention_name>
    <description>Intratumoral</description>
    <arm_group_label>Arm A: Tavo-EP, pembrolizumab, epacadostat</arm_group_label>
    <arm_group_label>Arm B: Tavo-EP, pembrolizumab</arm_group_label>
    <arm_group_label>Arm C: Tavo-EP, pembrolizumab, CORVax</arm_group_label>
    <other_name>Electroporation</other_name>
    <other_name>electroporation therapy (EPT)</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Epacadostat</intervention_name>
    <description>Given PO</description>
    <arm_group_label>Arm A: Tavo-EP, pembrolizumab, epacadostat</arm_group_label>
    <other_name>INCB 024360</other_name>
    <other_name>INCB024360</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Given IV</description>
    <arm_group_label>Arm A: Tavo-EP, pembrolizumab, epacadostat</arm_group_label>
    <arm_group_label>Arm B: Tavo-EP, pembrolizumab</arm_group_label>
    <arm_group_label>Arm C: Tavo-EP, pembrolizumab, CORVax</arm_group_label>
    <other_name>Keytruda</other_name>
    <other_name>Lambrolizumab</other_name>
    <other_name>MK-3475</other_name>
    <other_name>SCH 900475</other_name>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CORVax</intervention_name>
    <description>Intratumoral</description>
    <arm_group_label>Arm C: Tavo-EP, pembrolizumab, CORVax</arm_group_label>
    <other_name>DNA-encodable coronaviral vaccine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tavokinogene telseplasmid</intervention_name>
    <description>Intratumoral</description>
    <arm_group_label>Arm A: Tavo-EP, pembrolizumab, epacadostat</arm_group_label>
    <arm_group_label>Arm B: Tavo-EP, pembrolizumab</arm_group_label>
    <arm_group_label>Arm C: Tavo-EP, pembrolizumab, CORVax</arm_group_label>
    <other_name>Tavo-EP</other_name>
    <other_name>DNA plasmid</other_name>
    <other_name>plasmid IL-12 pUMVC3-hIL-12-NGVL3</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt;= 18 years old.&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status 0-2.&#xD;
&#xD;
          -  Life expectancy of at least 4 months.&#xD;
&#xD;
          -  Patients must have histological or cytological diagnosis of cancer originating in the&#xD;
             head and neck that is not amenable to surgical resection or locoregional radiation&#xD;
             therapy with curative intent.&#xD;
&#xD;
          -  At least one accessible lesion (AL) for intratumoral injection. An AL is defined as&#xD;
             meeting the following criteria; (1) at least 0.3 cm x 0.3 cm in longest perpendicular&#xD;
             diameters (2) in a suitable location for application of electroporation. Tumors&#xD;
             invading the carotid artery or at other sites that the investigator believes to be at&#xD;
             high risk of life-threatening hemorrhage should not be injected and these lesions may&#xD;
             not be used to meet the inclusion criterion for injectable lesions.&#xD;
&#xD;
          -  Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST)&#xD;
             v1.1; at least one lesion where the longest perpendicular diameter is at least 1.0 cm&#xD;
             by clinical measurement; or at least 1.0 cm by radiographic imaging for non-nodal&#xD;
             lesions; at least 1.5 cm in short axis by radiographic imaging for malignant lymph&#xD;
             nodes; If the biopsied lesions were previously irradiated, they must demonstrate&#xD;
             either radiographic or pathological evidence of recurrent or residual disease. It is&#xD;
             not necessary that this lesion is also an AL.&#xD;
&#xD;
          -  If patient has known brain metastases, they must have stable neurologic status&#xD;
             following local therapy (surgery or radiation) for at least 4 weeks without the use of&#xD;
             steroids or on stable or decreasing dose of &lt;=10 mg daily prednisone (or equivalent),&#xD;
             and must be without neurologic dysfunction that would confound the evaluation of&#xD;
             neurologic and other adverse events (AEs) (patients with a history of carcinomatous&#xD;
             meningitis are not eligible).&#xD;
&#xD;
          -  Patients may have had prior chemotherapy or immunotherapy or radiation therapy. Any&#xD;
             drug related adverse events identified during prior therapy must be well controlled&#xD;
             (typically resolution to =&lt; grade 1, OR resolved upon investigator review prior to&#xD;
             initiation of this therapy.&#xD;
&#xD;
          -  No systemic antineoplastic therapy may be received by the patient between the time of&#xD;
             the biopsy and the first administration of study treatment.&#xD;
&#xD;
          -  Patient must agree to any protocol mandated biopsies of tumor (deemed accessible and&#xD;
             safe for biopsy by the investigator's assessment) and they must allow acquired tissue&#xD;
             to be used for biomarker analysis.&#xD;
&#xD;
          -  For women of childbearing potential, negative serum or urine pregnancy test within 14&#xD;
             days of first dose of study drug(s) and use of birth control from 30 days prior to the&#xD;
             first study drug administration and 120 days following last administration of study&#xD;
             drug, or for participants in Arm C, 180 days after last dose of CORVax, whichever is&#xD;
             longer.&#xD;
&#xD;
          -  Male patients must be surgically sterile or must agree to use contraception during the&#xD;
             study and at least 120 days following the last administration of study drug, or for&#xD;
             participants in Arm C, 180 days after last dose of CORVax, whichever is longer.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic treatment in past 2 years.&#xD;
             Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency) is not considered a form&#xD;
             of systemic treatment.&#xD;
&#xD;
          -  Congestive heart failure (New York Heart Association class III to IV)&#xD;
&#xD;
          -  History or presence of an abnormal electrocardiogram (ECG) that, in the investigator's&#xD;
             opinion, is clinically meaningful. Screening corrected QT (QTc) interval &gt; 480&#xD;
             milliseconds is excluded. In the event that a single QTc is &gt; 480 milliseconds, the&#xD;
             subject may enroll if the average QTc for the 3 ECGs is &lt; 480 milliseconds. For&#xD;
             subjects with an intraventricular conduction delay (QRS interval &gt; 120 milliseconds),&#xD;
             the corrected JT (JTc) interval may be used in place of the QTc with sponsor approval.&#xD;
             The JTc must be &lt; 340 milliseconds if JTc is used in place of the QTc. Subjects with&#xD;
             left bundle branch block are excluded.&#xD;
&#xD;
          -  Uncontrolled or clinically significant conduction abnormalities (e.g., ventricular&#xD;
             tachycardia on anti-arrhythmics are excluded), 1st degree atrioventricular (AV) block&#xD;
             or asymptomatic left anterior fascicular block (LAFB)/right bundle branch block (RBBB)&#xD;
             are eligible.&#xD;
&#xD;
          -  Uncontrolled, symptomatic ischemia within 6 months of first dose of study treatment or&#xD;
             known myocardial infarction in the previous six months.&#xD;
&#xD;
          -  Patients with electronic pacemakers or defibrillators.&#xD;
&#xD;
          -  Has history of (non-infectious) pneumonitis/interstitial lung disease that required&#xD;
             steroids or has current pneumonitis/interstitial lung disease.&#xD;
&#xD;
          -  Any other current or previous malignancy within the past 2 years that, in the opinion&#xD;
             of the principal investigator will interfere with study-specific endpoints.&#xD;
&#xD;
          -  Evidence of significant active infection (e.g., pneumonia, cellulitis, wound abscess,&#xD;
             etc.) requiring systemic therapy at time of study enrollment.&#xD;
&#xD;
          -  Hepatitis B: Most nasopharyngeal cancer (NPC) patients have been infected with&#xD;
             hepatitis B (Cancer Epidemol Biomarkers Prev. 2015. 24:1766-73, N = 711) and,&#xD;
             therefore, the inclusion of healthy patients with a history of hepatitis B is a&#xD;
             central part of this study. In addition, programmed cell death protein 1 (PD-1)&#xD;
             antibodies have been proven to be safe in patients with active hepatitis and&#xD;
             hepatocellular carcinoma (e.g. KEYNOTE 224). However, patients with hepatitis B virus&#xD;
             (HBV) surface antigen positive (HBSAg) must have aspartate aminotransferase (AST) and&#xD;
             total bilirubin &lt; 1.5 x upper limit of normal (ULN) AND&#xD;
&#xD;
          -  Negative HBV ribonucleic acid (RNA) polymerase chain reaction (PCR) OR&#xD;
&#xD;
          -  On antivirals for HBV AND at least 8 weeks of prior anti-PD-1 antibody therapy AND no&#xD;
             history of AST or total bilirubin levels &gt; 1.5 x ULN due to PD-1 antibody therapy&#xD;
&#xD;
          -  Hepatitis C (hepatitis C virus (HCV) RNA (qualitative) is detected).&#xD;
&#xD;
          -  Presence of a gastrointestinal condition that may affect drug absorption.&#xD;
             Administration of epacadostat through a feeding tube is permitted.&#xD;
&#xD;
          -  Patients receiving systemic steroid therapy for a chronic inflammatory condition.&#xD;
             Topical steroids, nasal and inhaled steroids are permitted. Prednisone or equivalent&#xD;
             =&lt; 10 mg/day is permitted as hormone replacement; higher dosage prednisone should be&#xD;
             stopped at least 14 days prior to course 1 day 1 (C1D1).&#xD;
&#xD;
          -  Receipt of a live vaccine or live attenuated vaccine within 30 days before the first&#xD;
             dose of study treatment. Administration of killed vaccines is allowed.&#xD;
&#xD;
          -  Subjects receiving monoamine oxidase inhibitors (MAOIs) or drug which has significant&#xD;
             MAOI activity (meperidine, linezolid, methylene blue) within the 21 days before&#xD;
             screening.&#xD;
&#xD;
          -  Any history of serotonin syndrome (SS) after receiving serotonergic drugs.&#xD;
&#xD;
          -  Use of any uridine 5'-diphospho-glucuronosyltransferase 1-9 (UGT1A9) inhibitor from&#xD;
             screening through follow-up period, including the following: diclofenac, imipramine,&#xD;
             ketoconazole, mefenamic acid, and probenecid.&#xD;
&#xD;
          -  Known allergy or reaction to any component of study drug formulation.&#xD;
&#xD;
          -  Absolute neutrophil count (ANC) &lt; 1.0 x 10^9/L.&#xD;
&#xD;
          -  Platelets &lt; 75 x 10^9/L.&#xD;
&#xD;
          -  Hemoglobin &lt; 9 g/dL or &lt; 5.6 mmol/L (transfusion is acceptable to meet this&#xD;
             criterion).&#xD;
&#xD;
          -  Serum creatinine &gt;= 1.5 x institutional upper limit of normal (ULN) OR measured or&#xD;
             calculated creatinine clearance [glomerular filtration rate can also be used in place&#xD;
             of creatinine or creatinine clearance (CrCl)] &lt; 50 mL/min for subjects with creatinine&#xD;
             levels &gt; 1.5 x institutional ULN.&#xD;
&#xD;
          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) &gt; 2.5 x&#xD;
             institutional ULN.&#xD;
&#xD;
          -  Alkaline phosphatase &gt; 2.5 x ULN. Note: Subjects with 1) bone metastases and&#xD;
             gamma-glutamyl transpeptidase (GGT) &lt; 2.5 x ULN may enroll if the alkaline phosphatase&#xD;
             is &lt; 5 x ULN.&#xD;
&#xD;
          -  Total bilirubin above 1.5 x the institutional ULN AND conjugated bilirubin &gt;= 2.0 x&#xD;
             ULN.&#xD;
&#xD;
          -  International normalized ratio (INR) or prothrombin time (PT) &gt; 1.5 x ULN.&#xD;
&#xD;
          -  Activated partial thromboplastin time (aPTT) &gt; 1.5 x ULN.&#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>Chase Heaton, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 28, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 30, 2019</study_first_posted>
  <results_first_submitted>March 20, 2023</results_first_submitted>
  <results_first_submitted_qc>April 17, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">May 9, 2023</results_first_posted>
  <last_update_submitted>April 17, 2023</last_update_submitted>
  <last_update_submitted_qc>April 17, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Francisco</investigator_affiliation>
    <investigator_full_name>Chase Heaton, MD</investigator_full_name>
    <investigator_title>Asst Clinical Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>August 12, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/31/NCT03823131/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Enrollment in Arm A was terminated earlier than expected. Arms B and Arm C were never opened for enrollment.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
        </group>
        <group group_id="P2">
          <title>Arm B: Tavo-EP, Pembrolizumab</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.</description>
        </group>
        <group group_id="P3">
          <title>Arm C: Tavo-EP, Pembrolizumab, CORVax</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>The safety and efficacy analysis population is defined as all enrolled subjects who received at least one dose of study treatment.</population>
      <group_list>
        <group group_id="B1">
          <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
        </group>
        <group group_id="B2">
          <title>Arm B: Tavo-EP, Pembrolizumab</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Arm C: Tavo-EP, Pembrolizumab, CORVax</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="14"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="0"/>
            <count group_id="B4" value="14"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>30-39 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>40-49 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>50-59 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>60-69 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>70-79 years old</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="3"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="12"/>
                  </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="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" 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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Best Overall Response Rate</title>
        <description>The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.</description>
        <time_frame>Up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Best Overall Response Rate</title>
          <description>The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Months of Progression-Free Survival (PFS)</title>
        <description>Progression-free survival will be calculated as number of months from the first dosing date until the date of disease progression (i.e the date of the tumor imaging following baseline per central imaging assessment by a radiologist) or death from any cause. Per RECIST version 1.1, Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants who do not have documented disease progression will have their months of PFS censored on the last date of tumor assessment, or death, whichever comes first. Censoring data on date of last tumor imaging to calculate the median PFS will not occur until the overall survival data collection for all participants has been completed.</description>
        <time_frame>Up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Months of Progression-Free Survival (PFS)</title>
          <description>Progression-free survival will be calculated as number of months from the first dosing date until the date of disease progression (i.e the date of the tumor imaging following baseline per central imaging assessment by a radiologist) or death from any cause. Per RECIST version 1.1, Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants who do not have documented disease progression will have their months of PFS censored on the last date of tumor assessment, or death, whichever comes first. Censoring data on date of last tumor imaging to calculate the median PFS will not occur until the overall survival data collection for all participants has been completed.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.76" lower_limit="0.89" upper_limit="5.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Overall Survival (OS)</title>
        <description>Overall survival (OS) is defined as the number of months from the date of enrollment until the date of death regardless of cause, last date of follow-up, or date of study closure (if still alive), whichever comes first. Median months of overall participant survival will be reported using descriptive statistics.</description>
        <time_frame>Up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Overall Survival (OS)</title>
          <description>Overall survival (OS) is defined as the number of months from the date of enrollment until the date of death regardless of cause, last date of follow-up, or date of study closure (if still alive), whichever comes first. Median months of overall participant survival will be reported using descriptive statistics.</description>
          <units>months</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.6" lower_limit="1.02" upper_limit="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Time to Response</title>
        <description>Time to response is defined as the number of days from the date of enrollment to the date of the first documented response of CR or PR. The median time to response will be summarized by descriptive statistics.</description>
        <time_frame>Up to 36 months</time_frame>
        <population>No participants achieved an objective response, therefore a time to response could not be calculated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Time to Response</title>
          <description>Time to response is defined as the number of days from the date of enrollment to the date of the first documented response of CR or PR. The median time to response will be summarized by descriptive statistics.</description>
          <population>No participants achieved an objective response, therefore a time to response could not be calculated.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Disease Control Rate (DCR)</title>
        <description>The disease control rate is defined as the best response recorded from the start of treatment including stable disease, until disease progression/recurrence (PD). Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The proportion of participants relative to the total size of the All Treated Subjects population having a demonstrated response of CR, PR, or SD, with a confirmatory scan will be reported.</description>
        <time_frame>Up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Disease Control Rate (DCR)</title>
          <description>The disease control rate is defined as the best response recorded from the start of treatment including stable disease, until disease progression/recurrence (PD). Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to &lt;10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The proportion of participants relative to the total size of the All Treated Subjects population having a demonstrated response of CR, PR, or SD, with a confirmatory scan will be reported.</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Complete Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Partial Response</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Stable Disease</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Clinical Benefit Rate (CBR)</title>
        <description>Clinical benefit rate (CBR) is defined as the percentage of participants who achieved a best overall response of CR, PR and SD with a duration of response lasting at least 6 months or longer.</description>
        <time_frame>Up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Benefit Rate (CBR)</title>
          <description>Clinical benefit rate (CBR) is defined as the percentage of participants who achieved a best overall response of CR, PR and SD with a duration of response lasting at least 6 months or longer.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Duration of Response</title>
        <description>The duration of response (DOR) will be calculated for participants who achieved a best overall response of CR or PR and calculated as the number of days from the date when CR or PR is first confirmed to the date of progression or death. Participants who do not have a documented progression or death will be censored on the last date of tumor assessment. The median DOR and 95% confidence intervals will be reported.</description>
        <time_frame>Up to 36 months</time_frame>
        <population>No participants achieved an objective response, therefore a duration of response could not be calculated.</population>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Median Duration of Response</title>
          <description>The duration of response (DOR) will be calculated for participants who achieved a best overall response of CR or PR and calculated as the number of days from the date when CR or PR is first confirmed to the date of progression or death. Participants who do not have a documented progression or death will be censored on the last date of tumor assessment. The median DOR and 95% confidence intervals will be reported.</description>
          <population>No participants achieved an objective response, therefore a duration of response could not be calculated.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proportion of Participants With Reported Treatment-related Adverse Events (AEs)</title>
        <description>The proportion of participants with reported treatment-related adverse events, which are adverse events defined as having an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 will be reported.</description>
        <time_frame>Up to 36 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
            <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</description>
          </group>
        </group_list>
        <measure>
          <title>Proportion of Participants With Reported Treatment-related Adverse Events (AEs)</title>
          <description>The proportion of participants with reported treatment-related adverse events, which are adverse events defined as having an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 will be reported.</description>
          <units>proportion of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 36 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm A: Tavo-EP, Pembrolizumab, Epacadostat</title>
          <description>Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks, for up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.</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="9" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Blood and lymphatic system disorders, Other</sub_title>
                <description>Aspiration of blood into airway due to disease progression</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Edema, Face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Psychiatric disorders - Other</sub_title>
                <description>Altered mental status</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Pneumonitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pneumothorax</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </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="14" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>External ear inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>External ear pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gastroesophageal reflux disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dry Mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Nasuea</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Fever</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Injection site reaction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Chills</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Edema face</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Localized edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Gait Disturbance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other</sub_title>
                <description>Restless leg during evenings</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other</sub_title>
                <description>Tingling sensation in earlobe</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>General disorders and administration site conditions - Other</sub_title>
                <description>Discharge from tumor</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic Reaction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Sepsis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Tracheostomy site bleeding</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Generalized muscle weakness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Back pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Tumor Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dysgeusia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Anosmia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Insomnia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nasal congestion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Dyspnea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Epistaxis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Hyperhidrosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Skin and subcutaneous tissue disorders - Other</sub_title>
                <description>Intermittent rash</description>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="14"/>
              </event>
              <event>
                <sub_title>Pruritus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="14"/>
              </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>
    <limitations_and_caveats>The study closed earlier than expected during enrollment into Arm A. Arm B and Arm C were never opened to accrual.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Dr Chase Heaton, MD</name_or_title>
      <organization>University of California, San Francisco</organization>
      <phone>(415) 502-1889</phone>
      <email>Chase.Heaton@ucsf.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/NCT03823131
org study id: 172021
secondary id: NCI-2018-02901
nct id: NCT03823131
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
This phase II trial studies how well tavokinogene telseplasmid with electroporation
      (tavo-EP), pembrolizumab, and epacadostat work in treating patients with squamous cell
      carcinoma of the head and neck that cannot be removed by surgery. Tavokinogene telseplasmid
      with electroporation is a gene therapy that may delay of tumor growth and which may have less
      toxicity than other methods of gene delivery. Immunotherapy with monoclonal antibodies, such
      as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with
      the ability of tumor cells to grow and spread. Epacadostat may stop the growth of tumor cells
      by blocking some of the enzymes needed for cell growth. Giving tavokinogene telseplasmid with
      electroporation, pembrolizumab, and epacadostat may work better in treating squamous cell
      carcinoma of the head and neck.
PRIMARY OBJECTIVES:

      I. Dose Escalation Safety Lead-Ins: Assess the safety of tavo-EP and pembrolizumab in
      combination with epacadostat (CTCAE version 4).

      II. Dose Expansion: Determine whether the combination therapy in each arm increases the best
      overall response rate (BORR) compared with historical data for pembrolizumab monotherapy

      SECONDARY OBJECTIVES:

      I. Dose Expansion: Determine the durability of clinical benefits in participants treated with
      combination therapy in each arm, as assessed by time to progression, median progression-free
      survival (PFS), median overall survival (OS).

      EXPLORATORY OBJECTIVES:

      I. Determine the effects of combination therapy on treated and untreated lesions by examining
      paired biopsy specimens for changes in inflammatory gene expression, relative proportion of
      effector versus regulatory T cells, evaluation of inflammatory cytokines, T-cell activation,
      clonality, and other hallmarks of immune activation.

      II. Explore systemic markers of immune activation by examining circulating T-cell populations
      for changes in the frequency and effector function of short-lived effector cells and memory T
      cells.

      III. Explore changes in functional immune responses using Elispot and other assays.

      IV. To explore biomarkers that inform scientific understanding of this therapeutic treatment
      through analysis of specimens retained for Future Biomedical Research.

      OUTLINE:

      This is a multi-center, open label, 2-stage, double-arm, clinical trial in which participants
      in Stage 1 will receive either tavo-EP with pembrolizumab, and epacadostat (Arm A), tavo-EP
      and pembrolizumab (Arm B), or CORVax, tavo-EP and pembrolizumab (Arm C). Arms B and C will
      only open to enrollment if the treatment is determined to be effective in Arm A.

      Participants will be followed at 3-month intervals for toxicity and radiographic imaging (1)
      until start of a new anti-cancer treatment, (2) until 30 days after documented disease
      progression, (3) until death, or (4) until 36 months from the initiation of treatment on
      study, whichever comes first. Each subject will be followed for overall survival until death,
      withdrawal of consent, or at the time of study closure, whichever occurs first.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Best Overall Response Rate
time frame: Up to 36 months
description: The best overall response (BORR) is defined as the best response recorded from the start of treatment until disease progression/recurrence. Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. The combined percentage of participants relative to the total size of the All Treated Subjects population having a demonstrated best response of CR or PR, with a confirmatory scan will be reported.
measure: Median Months of Progression-Free Survival (PFS)
time frame: Up to 36 months
description: Progression-free survival will be calculated as number of months from the first dosing date until the date of disease progression (i.e the date of the tumor imaging following baseline per central imaging assessment by a radiologist) or death from any cause. Per RECIST version 1.1, Progressive Disease (PD) is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants who do not have documented disease progression will have their months of PFS censored on the last date of tumor assessment, or death, whichever comes first. Censoring data on date of last tumor imaging to calculate the median PFS will not occur until the overall survival data collection for all participants has been completed.
measure: Median Overall Survival (OS)
time frame: Up to 36 months
description: Overall survival (OS) is defined as the number of months from the date of enrollment until the date of death regardless of cause, last date of follow-up, or date of study closure (if still alive), whichever comes first. Median months of overall participant survival will be reported using descriptive statistics.
measure: Median Time to Response
time frame: Up to 36 months
description: Time to response is defined as the number of days from the date of enrollment to the date of the first documented response of CR or PR. The median time to response will be summarized by descriptive statistics.
measure: Disease Control Rate (DCR)
time frame: Up to 36 months
description: The disease control rate is defined as the best response recorded from the start of treatment including stable disease, until disease progression/recurrence (PD). Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Complete Response (CR) is defined as the disappearance of all target lesions and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is defined as having at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD) is defined as having neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The proportion of participants relative to the total size of the All Treated Subjects population having a demonstrated response of CR, PR, or SD, with a confirmatory scan will be reported.
measure: Clinical Benefit Rate (CBR)
time frame: Up to 36 months
description: Clinical benefit rate (CBR) is defined as the percentage of participants who achieved a best overall response of CR, PR and SD with a duration of response lasting at least 6 months or longer.
measure: Median Duration of Response
time frame: Up to 36 months
description: The duration of response (DOR) will be calculated for participants who achieved a best overall response of CR or PR and calculated as the number of days from the date when CR or PR is first confirmed to the date of progression or death. Participants who do not have a documented progression or death will be censored on the last date of tumor assessment. The median DOR and 95% confidence intervals will be reported.
measure: Proportion of Participants With Reported Treatment-related Adverse Events (AEs)
time frame: Up to 36 months
description: The proportion of participants with reported treatment-related adverse events, which are adverse events defined as having an attribution of possible, probable, or definite according to NCI Common Terminology Criteria for Adverse Events (CTCAE) v. 4 will be reported.
arm group label: Arm A: Tavo-EP, pembrolizumab, epacadostat
arm group type: Experimental
description: Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks. Epacadostat will be administered at the dose level determined in the dose escalation safety lead-in.
arm group label: Arm B: Tavo-EP, pembrolizumab
arm group type: Experimental
description: Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30 minute IV infusion at a dose of 200 mg every 3 weeks.
arm group label: Arm C: Tavo-EP, pembrolizumab, CORVax
arm group type: Experimental
description: Tavo-EP will be injected intratumorally on Days 1, 5 and 8 every 6 weeks to up to 7 accessible lesions without exceeding 20 mL per day. Injected lesions will then be electroporated using the ImmunoPulse electroporation device. Pembrolizumab will be administered by a 30-minute IV infusion at a dose of 200 mg every 3 weeks. CORVax will be administered at a total dose of 0.2 mg of (S) protein plasmid in 120 microliter (uL) per lesion intratumorally into a maximum of 4 lesions of at least 0.3 mm in diameter for a total plasmid dose of 0.8 mg on treatment days 1 and 29 of cycle 1 followed by electroporation of the plasmid solution in infiltrated regions. On days when both tavo and CORVax is administered to the same lesions, tavo and CORVax will each be injected into the lesion followed by electroporation.
intervention type: Device
intervention name: ImmunoPulse
description: Intratumoral
arm group label: Arm A: Tavo-EP, pembrolizumab, epacadostat
arm group label: Arm B: Tavo-EP, pembrolizumab
arm group label: Arm C: Tavo-EP, pembrolizumab, CORVax
other name: Electroporation
other name: electroporation therapy (EPT)
intervention type: Drug
intervention name: Epacadostat
description: Given PO
arm group label: Arm A: Tavo-EP, pembrolizumab, epacadostat
other name: INCB 024360
other name: INCB024360
intervention type: Drug
intervention name: Pembrolizumab
description: Given IV
arm group label: Arm A: Tavo-EP, pembrolizumab, epacadostat
arm group label: Arm B: Tavo-EP, pembrolizumab
arm group label: Arm C: Tavo-EP, pembrolizumab, CORVax
other name: Keytruda
other name: Lambrolizumab
other name: MK-3475
other name: SCH 900475
intervention type: Biological
intervention name: CORVax
description: Intratumoral
arm group label: Arm C: Tavo-EP, pembrolizumab, CORVax
other name: DNA-encodable coronaviral vaccine
intervention type: Drug
intervention name: Tavokinogene telseplasmid
description: Intratumoral
arm group label: Arm A: Tavo-EP, pembrolizumab, epacadostat
arm group label: Arm B: Tavo-EP, pembrolizumab
arm group label: Arm C: Tavo-EP, pembrolizumab, CORVax
other name: Tavo-EP
other name: DNA plasmid
other name: plasmid IL-12 pUMVC3-hIL-12-NGVL3
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Chase Heaton, MD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of California, San Francisco
investigator full name: Chase Heaton, MD
investigator title: Asst Clinical Professor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Pembrolizumab
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study closed earlier than expected during enrollment into Arm A. Arm B and Arm C were never opened to accrual.
point of contact: 