xml: <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/NCT05977907</url>
    </required_header>
    <id_info>
      <org_study_id>J22106</org_study_id>
      <nct_id>NCT05977907</nct_id>
    </id_info>
    <brief_title>Neoadjuvant Pembrolizumab and IO102-103 for Squamous Cell Carcinoma of the Head and Neck (SCCHN).</brief_title>
    <acronym>KIEO</acronym>
    <official_title>Neoadjuvant Pembrolizumab and IO102-103 Prior to Curative-intent Surgical Care for Squamous Cell Carcinoma of the Head and Neck (SCCHN)</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>IO Biotech</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
      <collaborator>
        <agency>Merck Sharp &amp; Dohme LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This research is being done to see if it is safe to give investigational combination of study&#xD;
        drugs (Pembrolizumab and IO102-103) before surgery to people with surgically resectable&#xD;
        (removable) newly diagnosed or recurrent metastatic SCCHN. This will be done by watching&#xD;
        participants closely for possible side effects from Pembrolizumab and IO102-103. In addition,&#xD;
        participants will be monitored for any delays to their surgery due to the study drugs.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 1, 2023</start_date>
    <completion_date type="Anticipated">September 1, 2028</completion_date>
    <primary_completion_date type="Anticipated">September 1, 2026</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>All participants receive same dose of drug. One Cohort</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Pathologic Treatment Response rate</measure>
      <time_frame>From neoadjuvant therapy to surgical resection, up to 6 weeks</time_frame>
      <description>To determine rate of pathologic treatment response ≥50% (pTR-2) / immune-related pathologic response criteria (irPRC) ≥ 50% rate to neoadjuvant pembrolizumab plus IO102-IO103 in SCCHN</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Major Pathologic Response</measure>
      <time_frame>From neoadjuvant therapy to surgical resection, up to 6 weeks</time_frame>
      <description>To determine the rate of major pathologic response with the neoadjuvant treatment approach</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Disease progression</measure>
      <time_frame>From neoadjuvant therapy to surgical resection, up to 6 weeks</time_frame>
      <description>To determine progression-free survival in patients treated with immunotherapy-based neoadjuvant therapy followed by surgical resection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall survival</measure>
      <time_frame>From neoadjuvant therapy to surgical resection, up to 6 weeks</time_frame>
      <description>To determine overall survival in patients treated with immunotherapy-based neoadjuvant therapy followed by surgical resection</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Safety</measure>
      <time_frame>Up to 100 days after the last dose of study drug</time_frame>
      <description>To determine the safety and feasibility of the proposed treatment approach including severe adverse events (SAEs), AEs related treatment/surgery delays, and treatment related mortality. AEs and other toxicities will be graded using NCI Common Terminology Criteria for Adverse Events 5.0 (CTCAE)</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>ctDNA in comparison to other neoadjuvant treatments</measure>
      <time_frame>5 years</time_frame>
      <description>To determine circulating tumor DNA (ctDNA) ≥50% response rate compared to another anti-Programed Cell Death protein 1 (PD-1) treated neoadjuvant cohort</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">15</enrollment>
    <condition>Head and Neck Squamous Cell Carcinoma</condition>
    <arm_group>
      <arm_group_label>Single Cohort</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Neoadjuvant Pembrolizumab ( 400mg IV infusion x1) + IO102-103 ( Subcutaneous injection weekly x6)&#xD;
  Adjuvant Pembrolizumab ( 400 mg IV infusion Every 6 weeks x8) + IO102-103 ( Subcutaneous injection every 3 week x6 then every 6 weeks x5)</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Pembrolizumab is an investigational drug in this study</description>
      <arm_group_label>Single Cohort</arm_group_label>
      <other_name>Keytruda</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>IO102-103</intervention_name>
      <description>IO102-103 is an investigational drug in this study.</description>
      <arm_group_label>Single Cohort</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Be willing and able to provide written informed consent/assent for the trial.&#xD;
  &#xD;
            -  Be 18 years of age on day of signing informed consent.&#xD;
  &#xD;
            -  Patients with non-bulky/non-bulky squamous cell carcinomas of the head and neck, with&#xD;
               an indication for surgical therapy.&#xD;
  &#xD;
                 1. Surgically resectable disease - generally that is T1N1-N2B, T2-4N0-N2b stage are&#xD;
                    generally eligible (AJCC 7th), however exceptions can be made after approval by&#xD;
                    the PI for surgically appropriate cases.&#xD;
  &#xD;
                 2. If determined per tumor board that a low-volume/non-bulky tumor of another stage&#xD;
                    is appropriate for resection (e.g. small volume T4 with a small amount of bone&#xD;
                    invasion) such tumors may also be considered for this study if recommendation in&#xD;
                    tumor board is such.&#xD;
  &#xD;
            -  Be appropriate candidates for resection and curative intent therapy in general.&#xD;
  &#xD;
            -  Have a performance status of 0 or 1 on the ECOG Performance Scale.&#xD;
  &#xD;
            -  Consent to undergo biopsy from a newly obtained core or excisional biopsy of a tumor&#xD;
               lesion before study drug administration, and during treatment. Biopsy in case of&#xD;
               progressive disease is optional.&#xD;
  &#xD;
            -  Demonstrate adequate organ function&#xD;
  &#xD;
            -  Female subject of childbearing potential should have a negative urine or serum&#xD;
               pregnancy within 72 hours prior to receiving the first dose of study medication. If&#xD;
               the urine test is positive or cannot be confirmed as negative, a serum pregnancy test&#xD;
               will be required.&#xD;
  &#xD;
            -  Female subjects of childbearing potential should be willing to use 2 methods of birth&#xD;
               control or be surgically sterile or abstain from heterosexual activity for the course&#xD;
               of the study through 120 days after the last dose of study medication. Subjects of&#xD;
               childbearing potential are those who have not been surgically sterilized or have not&#xD;
               been free from menses for &gt; 1 year.&#xD;
  &#xD;
            -  Male subjects should agree to use an adequate method of contraception starting with&#xD;
               the first dose of study therapy through 120 days after the last dose of study therapy.&#xD;
  &#xD;
                 1. Abstinence is considered an adequate contraception method.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  A Women of child bearing potential (WOCBP) who has a positive urine pregnancy test&#xD;
               within 72 hours prior to treatment allocation/registration . If the urine test is&#xD;
               positive or cannot be confirmed as negative, a serum pregnancy test will be required.&#xD;
  &#xD;
            -  Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with&#xD;
               an agent directed to another stimulatory or co-inhibitory T-cell receptor&#xD;
  &#xD;
            -  Has received prior systemic anti-cancer therapy for HNSCC including investigational&#xD;
               agents within 4 weeks of first dose of study treatment.&#xD;
  &#xD;
            -  Has received prior radiotherapy within 2 weeks of start of study intervention.&#xD;
               Participants must have recovered from all radiation-related toxicities, not require&#xD;
               corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted&#xD;
               for palliative radiation (≤2 weeks of radiotherapy) to non- Central nervous system&#xD;
               (CNS) disease.&#xD;
  &#xD;
            -  Has received a live vaccine or live-attenuated vaccine within 30 days prior to the&#xD;
               first dose of study drug (including live COVID-19 vaccines). Administration of killed&#xD;
               vaccines is allowed. Administration of messenger RNA (mRNA) or peptide vaccines (e.g.,&#xD;
               for COVID-19) is allowed.&#xD;
  &#xD;
            -  Is currently participating in or has participated in a study of an investigational&#xD;
               agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
               study intervention.&#xD;
  &#xD;
            -  Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy&#xD;
               (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of&#xD;
               immunosuppressive therapy within 7 days prior to the first dose of study drug.&#xD;
  &#xD;
            -  Has a known additional malignancy that is progressing or has required active treatment&#xD;
               within the past 2 years. Participants with basal cell carcinoma of the skin, squamous&#xD;
               cell carcinoma of the skin, low grade cancers that are not expected to impact life&#xD;
               expectancy within the next 3 years and not impact interpretation of this study are&#xD;
               allowed&#xD;
  &#xD;
            -  Has known active CNS metastases and/or carcinomatous meningitis. Participants with&#xD;
               previously treated brain metastases may participate provided they are radiologically&#xD;
               stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging&#xD;
  &#xD;
            -  Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.&#xD;
  &#xD;
            -  Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
               (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
               drugs), unless it is systemic steroid therapy equal or less than outlined in exclusion&#xD;
               criteria 7.&#xD;
  &#xD;
          Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement .&#xD;
  &#xD;
          therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic&#xD;
          treatment and is allowed.&#xD;
  &#xD;
            -  Has a history of (non-infectious) pneumonitis/interstitial lung disease that required&#xD;
               steroids or has current pneumonitis/interstitial lung disease.&#xD;
  &#xD;
            -  Has an active infection requiring systemic therapy.&#xD;
  &#xD;
            -  Has a known history of Human Immunodeficiency Virus (HIV) infection.&#xD;
  &#xD;
            -  Has a known history of Hepatitis B or Hepatitis C virus&#xD;
  &#xD;
            -  Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
               that might confound the results of the study, interfere with the participant's&#xD;
               participation for the full duration of the study, or is not in the best interest of&#xD;
               the participant to participate, in the opinion of the treating investigator.&#xD;
  &#xD;
            -  Has known psychiatric or substance abuse disorders that would interfere with&#xD;
               cooperation with the requirements of the trial as per assessment of the treating&#xD;
               physician. Chronic managed disorders that are not clinically active are acceptable.&#xD;
  &#xD;
            -  Is pregnant or breastfeeding or expecting to conceive or father children within the&#xD;
               projected duration of the study, starting with the screening visit through 120 days&#xD;
               after the last dose of trial treatment.&#xD;
  &#xD;
            -  Has had an allogenic tissue/solid organ transplant.&#xD;
  &#xD;
            -  Congestive heart failure , unstable angina, serious uncontrolled cardiac arrhythmia, a&#xD;
               myocardial infarction within 6 months prior to study entry or a history of myocarditis&#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>Tanguy Seiwert, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Johns Hopkins University/Sidney Kimmel Cancer Center</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tanguy Seiwert, M.D.</last_name>
      <phone>443-287-8312</phone>
      <email>tseiwert@jhmi.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Zubair Khan, M.D.</last_name>
      <phone>410-955-3157</phone>
      <email>zkhan@jhmi.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Johns Hopkins University</name>
        <address>
          <city>Baltimore</city>
          <state>Maryland</state>
          <zip>21287</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Tanguy Seiwert, M.D</last_name>
        <phone>443-287-8312</phone>
        <email>tseiwert@jhmi.edu</email>
      </contact>
      <contact_backup>
        <last_name>Zubair Khan, M.D.</last_name>
        <phone>410-955-3157</phone>
        <email>zkhan@jhmi.edu</email>
      </contact_backup>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 25, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 2, 2023</last_update_submitted>
    <last_update_submitted_qc>August 2, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 7, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>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>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05977907
  org study id: J22106
  nct id: NCT05977907
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  This research is being done to see if it is safe to give investigational combination of study
        drugs (Pembrolizumab and IO102-103) before surgery to people with surgically resectable
        (removable) newly diagnosed or recurrent metastatic SCCHN. This will be done by watching
        participants closely for possible side effects from Pembrolizumab and IO102-103. In addition,
        participants will be monitored for any delays to their surgery due to the study drugs.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: All participants receive same dose of drug. One Cohort
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Pathologic Treatment Response rate
  time frame: From neoadjuvant therapy to surgical resection, up to 6 weeks
  description: To determine rate of pathologic treatment response ≥50% (pTR-2) / immune-related pathologic response criteria (irPRC) ≥ 50% rate to neoadjuvant pembrolizumab plus IO102-IO103 in SCCHN
  measure: Major Pathologic Response
  time frame: From neoadjuvant therapy to surgical resection, up to 6 weeks
  description: To determine the rate of major pathologic response with the neoadjuvant treatment approach
  measure: Disease progression
  time frame: From neoadjuvant therapy to surgical resection, up to 6 weeks
  description: To determine progression-free survival in patients treated with immunotherapy-based neoadjuvant therapy followed by surgical resection
  measure: Overall survival
  time frame: From neoadjuvant therapy to surgical resection, up to 6 weeks
  description: To determine overall survival in patients treated with immunotherapy-based neoadjuvant therapy followed by surgical resection
  measure: Overall Safety
  time frame: Up to 100 days after the last dose of study drug
  description: To determine the safety and feasibility of the proposed treatment approach including severe adverse events (SAEs), AEs related treatment/surgery delays, and treatment related mortality. AEs and other toxicities will be graded using NCI Common Terminology Criteria for Adverse Events 5.0 (CTCAE)
  measure: ctDNA in comparison to other neoadjuvant treatments
  time frame: 5 years
  description: To determine circulating tumor DNA (ctDNA) ≥50% response rate compared to another anti-Programed Cell Death protein 1 (PD-1) treated neoadjuvant cohort
  arm group label: Single Cohort
  arm group type: Experimental
  description: Neoadjuvant Pembrolizumab ( 400mg IV infusion x1) + IO102-103 ( Subcutaneous injection weekly x6)
  Adjuvant Pembrolizumab ( 400 mg IV infusion Every 6 weeks x8) + IO102-103 ( Subcutaneous injection every 3 week x6 then every 6 weeks x5)
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Pembrolizumab is an investigational drug in this study
  arm group label: Single Cohort
  other name: Keytruda
  intervention type: Drug
  intervention name: IO102-103
  description: IO102-103 is an investigational drug in this study.
  arm group label: Single Cohort
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Tanguy Seiwert, M.D.
  role: Principal Investigator
  affiliation: Johns Hopkins University/Sidney Kimmel Cancer Center
  last name: Tanguy Seiwert, M.D.
  phone: 443-287-8312
  email: tseiwert@jhmi.edu
  last name: Zubair Khan, M.D.
  phone: 410-955-3157
  email: zkhan@jhmi.edu
  facility: 
  contact: 
  contact backup: 
  country: United States
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Squamous Cell
  mesh term: Squamous Cell Carcinoma of Head and Neck
  mesh term: Pembrolizumab
  sharing ipd: No