<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/NCT03832855</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00104093</org_study_id>
    <nct_id>NCT03832855</nct_id>
  </id_info>
  <brief_title>Assessing the Immunogenicity of pING-hHER3FL</brief_title>
  <official_title>Assessing the Immunogenicity of pING-hHER3FL in Patients With Resected Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Herbert Lyerly</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a phase I clinical trial will that will use an investigational cancer vaccine&#xD;
      called pING-hHER3FL. pING-hHER3FL is a circular piece of DNA that produces the full length&#xD;
      human HER3 protein and will be used in a phase I study as immunotherapeutic agent to target&#xD;
      cancers that are known to express the human epidermal growth factor receptor HER3. The human&#xD;
      epidermal growth factor receptor (HER) family including: HER1 (also known as EGFR), HER2,&#xD;
      HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important receptor&#xD;
      family for the development of many malignancies. HER3 is overexpressed in breast, lung,&#xD;
      gastric, head and neck, ovarian cancer, and melanoma.&#xD;
&#xD;
      The objectives of this clinical study is to determine the safety and tolerability of&#xD;
      pING-hHER3FL in patients with solid tumor malignancies that have been removed surgically and&#xD;
      to test whether immunization with pING-hHER3FL can cause a HER3 specific immune response in&#xD;
      patients. Patients enrolled in the study will receive pING-hHER3FL by intramuscular injection&#xD;
      (IM) every 4 weeks for 3 total doses. Potential benefits of the research include learning the&#xD;
      safety of a vaccine targeting HER3 expressing cancers, whether the pING-hHER3FL vaccine can&#xD;
      induce HER3 specific immune responses, and see possible clinical benefit to patients&#xD;
      receiving pING-hHER3FL.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The human epidermal growth factor receptor (HER) family including HER1 (also known as EGFR),&#xD;
      HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important&#xD;
      receptor family for the development of many malignancies. HER3 is overexpressed in breast,&#xD;
      lung, gastric, head and neck, and ovarian cancer and melanoma and its overexpression is&#xD;
      associated with poor prognosis. Because of the negligible tyrosine kinase function of HER3,&#xD;
      it is typically present in heterodimers with HER1 or HER2, through which downstream signaling&#xD;
      occurs involving extracellular-signal-regulated kinase (ERK) 1/2 and AKT. In breast cancer,&#xD;
      HER3 is associated with resistance to anti-HER2 therapeutics. HER3 is also one of several&#xD;
      important causes of endocrine resistance in breast cancer.&#xD;
&#xD;
      A HER3 specific cancer vaccine that induces polyclonal antibody and T cell responses can&#xD;
      provide long term anti-HER3 immune responses and potentially prevent the emergence of&#xD;
      resistant clones. In addition to the long term protection afforded by vaccination, polyclonal&#xD;
      immune responses to a target protein may offer additional benefits. It has been established&#xD;
      that the binding of multiple antibodies to different epitopes is more efficient than a single&#xD;
      monoclonal antibody in mediating receptor internalization. Additionally, T cell responses&#xD;
      induced by vaccination are also a potent mechanism of tumor rejection in numerous animal&#xD;
      studies and the adoptive transfer of T cells in human clinical trials has shown clinical&#xD;
      efficacy. Although HER3 is expressed on a number of normal tissues, and is only rarely&#xD;
      mutated in cancers, it remains an attractive immunotherapeutic target as it is not abundant&#xD;
      on the cell surface in normal cells, tumor cells may have higher levels of membrane-bound&#xD;
      HER3, and HER3 peptides are presented on the cell surface by MHC complexes for presentation&#xD;
      to T cells.&#xD;
&#xD;
      The primary objective of the study is to evaluate the safety of immunization with pING-hHER3&#xD;
      in patients with solid tumor malignancies that have been removed surgically. The study will&#xD;
      also monitor immune responses to HER3 and preliminary data on survival and tumor response&#xD;
      rate will be collected.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 13, 2020</start_date>
  <completion_date type="Anticipated">December 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2023</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Rate of T and B cell activity</measure>
    <time_frame>12 months</time_frame>
    <description>B cell and T cell specific immune response to pING-hHER3FL vaccinationvaccination</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tolerability of pING-hHER3FL</measure>
    <time_frame>12 weeks</time_frame>
    <description>Assessment of adverse events in response to pING-hHER3FL</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Relapse-free survival</measure>
    <time_frame>5 years</time_frame>
    <description>Time until relapse of cancer</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>4 mg pING-hHER3FL ID or IM</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>pING-hHER3FL</intervention_name>
    <description>Plasmid vaccine containing HER3</description>
    <arm_group_label>Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Documented history of solid tumor where HER3 expression is expected (this includes&#xD;
             breast, colon, lung, prostate, ovarian, cervical, endometrial, gastric, pancreatic,&#xD;
             bladder, head and neck, liver, and esophageal cancer, but other tumors will be&#xD;
             considered based on emerging HER3 expression data in the literature). Demonstration of&#xD;
             HER3 expression is not required for enrollment.&#xD;
&#xD;
          -  Has undergone surgical resection of malignancy and has completed intended standard&#xD;
             course of chemotherapy and HER2 targeted therapy and radiotherapy under the direction&#xD;
             of their physician. Subjects may continue on adjuvant hormonal therapy.&#xD;
&#xD;
          -  Has no evidence of disease by standard imaging studies (performed at the direction of&#xD;
             their physician) within 60 days prior to initiating study treatment.&#xD;
&#xD;
          -  Between 3 weeks and 2 years since prior cytotoxic chemotherapy, HER2-targeted therapy&#xD;
             or radiotherapy to the start of study treatment.&#xD;
&#xD;
          -  ECOG 0 or 1&#xD;
&#xD;
          -  Estimated life expectancy &gt; 3 months.&#xD;
&#xD;
          -  Age ≥ 18 years.&#xD;
&#xD;
          -  Adequate hematologic function, with ANC &gt;1500/µL, Hemoglobin ≥ 9 g/dL, and Platelets ≥&#xD;
             75,000/µL.&#xD;
&#xD;
          -  Adequate renal and hepatic function, with Serum Creatinine &lt; 1.5 mg/dL, Bilirubin &lt;&#xD;
             1.5 mg/dL (except for Gilbert's syndrome which will allow bilirubin ≤ 2.0 mg/dL), ALT&#xD;
             and AST ≤ 2.5 x ULN or if liver metastases are present &lt; 5 x ULN.&#xD;
&#xD;
          -  Female patients must be of non-child-bearing potential or use effective contraception,&#xD;
             .&#xD;
&#xD;
          -  Labs performed as standard of care prior to signing consent can be used to fulfill&#xD;
             eligibility requirements if they were performed within 4 weeks of the start of study&#xD;
             treatment.&#xD;
&#xD;
          -  Ability to understand and provide signed informed consent.&#xD;
&#xD;
          -  Ability to return to the study site for adequate follow-up, as required by this&#xD;
             protocol.&#xD;
&#xD;
          -  Negative serum pregnancy test within 7 days prior to the start of study treatment, for&#xD;
             women of childbearing potential only.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients must have recovered to Grade 1 toxicities from any prior treatment(s).&#xD;
&#xD;
          -  Known CNS/brain metastases&#xD;
&#xD;
          -  History of auto-immune disease such as, but not restricted to, inflammatory bowel&#xD;
             disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or&#xD;
             multiple sclerosis.&#xD;
&#xD;
          -  Serious chronic or acute illness considered by the Principal Investigator to&#xD;
             constitute an unwarranted high risk for investigational treatment.&#xD;
&#xD;
          -  Medical or psychological impediment to probable compliance with the protocol.&#xD;
&#xD;
          -  Concurrent or prior second malignancy (within the past 5 years) other than&#xD;
             non-melanoma skin cancer, Carcinoma in situ of the bladder and cervix.&#xD;
&#xD;
          -  Presence of active infection or systemic use of antimicrobials within 48 hours prior&#xD;
             to the start of study treatment.&#xD;
&#xD;
          -  Patients on continuous steroid therapy for at least 72 hours (or other continuous&#xD;
             immunosuppressives such as azathioprine or cyclosporine A) are excluded on the basis&#xD;
             of potential immune suppression.&#xD;
&#xD;
          -  Presence of a known active acute or chronic infection including HIV or viral hepatitis&#xD;
             (Hepatitis B and C).&#xD;
&#xD;
          -  Pregnant or nursing women.&#xD;
&#xD;
          -  Prior immunotherapy&#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_contact>
    <last_name>Michael Morse, MD</last_name>
    <phone>919-684-5705</phone>
    <email>michael.morse@duke.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Beth Hollister, BSN, RN</last_name>
    <phone>919-681-2172</phone>
    <email>beth.hollister@duke.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>H. Kim Lyerly, MD</last_name>
      <phone>919-684-0132</phone>
      <email>kim.lyerly@duke.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>January 29, 2019</study_first_submitted>
  <study_first_submitted_qc>February 5, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 6, 2019</study_first_posted>
  <last_update_submitted>November 4, 2022</last_update_submitted>
  <last_update_submitted_qc>November 4, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Herbert Lyerly</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <keyword>Breast Cancer</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>HER2</keyword>
  <keyword>HER3</keyword>
  <keyword>T cell</keyword>
  <keyword>vaccine</keyword>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03832855
org study id: Pro00104093
nct id: NCT03832855
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This study is a phase I clinical trial will that will use an investigational cancer vaccine
      called pING-hHER3FL. pING-hHER3FL is a circular piece of DNA that produces the full length
      human HER3 protein and will be used in a phase I study as immunotherapeutic agent to target
      cancers that are known to express the human epidermal growth factor receptor HER3. The human
      epidermal growth factor receptor (HER) family including: HER1 (also known as EGFR), HER2,
      HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important receptor
      family for the development of many malignancies. HER3 is overexpressed in breast, lung,
      gastric, head and neck, ovarian cancer, and melanoma.

      The objectives of this clinical study is to determine the safety and tolerability of
      pING-hHER3FL in patients with solid tumor malignancies that have been removed surgically and
      to test whether immunization with pING-hHER3FL can cause a HER3 specific immune response in
      patients. Patients enrolled in the study will receive pING-hHER3FL by intramuscular injection
      (IM) every 4 weeks for 3 total doses. Potential benefits of the research include learning the
      safety of a vaccine targeting HER3 expressing cancers, whether the pING-hHER3FL vaccine can
      induce HER3 specific immune responses, and see possible clinical benefit to patients
      receiving pING-hHER3FL.
The human epidermal growth factor receptor (HER) family including HER1 (also known as EGFR),
      HER2, HER3 and HER4 (also known as ErbB2, ErbB3, and ErbB4 respectively) is an important
      receptor family for the development of many malignancies. HER3 is overexpressed in breast,
      lung, gastric, head and neck, and ovarian cancer and melanoma and its overexpression is
      associated with poor prognosis. Because of the negligible tyrosine kinase function of HER3,
      it is typically present in heterodimers with HER1 or HER2, through which downstream signaling
      occurs involving extracellular-signal-regulated kinase (ERK) 1/2 and AKT. In breast cancer,
      HER3 is associated with resistance to anti-HER2 therapeutics. HER3 is also one of several
      important causes of endocrine resistance in breast cancer.

      A HER3 specific cancer vaccine that induces polyclonal antibody and T cell responses can
      provide long term anti-HER3 immune responses and potentially prevent the emergence of
      resistant clones. In addition to the long term protection afforded by vaccination, polyclonal
      immune responses to a target protein may offer additional benefits. It has been established
      that the binding of multiple antibodies to different epitopes is more efficient than a single
      monoclonal antibody in mediating receptor internalization. Additionally, T cell responses
      induced by vaccination are also a potent mechanism of tumor rejection in numerous animal
      studies and the adoptive transfer of T cells in human clinical trials has shown clinical
      efficacy. Although HER3 is expressed on a number of normal tissues, and is only rarely
      mutated in cancers, it remains an attractive immunotherapeutic target as it is not abundant
      on the cell surface in normal cells, tumor cells may have higher levels of membrane-bound
      HER3, and HER3 peptides are presented on the cell surface by MHC complexes for presentation
      to T cells.

      The primary objective of the study is to evaluate the safety of immunization with pING-hHER3
      in patients with solid tumor malignancies that have been removed surgically. The study will
      also monitor immune responses to HER3 and preliminary data on survival and tumor response
      rate will be collected.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Rate of T and B cell activity
time frame: 12 months
description: B cell and T cell specific immune response to pING-hHER3FL vaccinationvaccination
measure: Tolerability of pING-hHER3FL
time frame: 12 weeks
description: Assessment of adverse events in response to pING-hHER3FL
measure: Relapse-free survival
time frame: 5 years
description: Time until relapse of cancer
arm group label: Treatment
arm group type: Experimental
description: 4 mg pING-hHER3FL ID or IM
intervention type: Biological
intervention name: pING-hHER3FL
description: Plasmid vaccine containing HER3
arm group label: Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Michael Morse, MD
phone: 919-684-5705
email: michael.morse@duke.edu
last name: Beth Hollister, BSN, RN
phone: 919-681-2172
email: beth.hollister@duke.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Herbert Lyerly
investigator title: Professor
sharing ipd: No