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/NCT05980598</url>
    </required_header>
    <id_info>
      <org_study_id>ASND0038</org_study_id>
      <nct_id>NCT05980598</nct_id>
    </id_info>
    <brief_title>TransCon (TC) TLR7/8 Agonist, TC IL-2 β/γ, Pembrolizumab Prior to Surgery for Advanced Head and Neck Squamous Cell Carcinoma</brief_title>
    <acronym>BelieveIT-201</acronym>
    <official_title>BelieveIT-201: Phase 2, Randomized Open-labeled Trial of TransCon (TC) TLR7/8 Agonist in Combination With Pembrolizumab or With TC IL-2 β/γ, or Pembrolizumab Alone as Neoadjuvant Therapy for Stage III-IVA Resectable Locoregionally Advanced Head and Neck Squamous Cell Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Ascendis Pharma Oncology Division A/S</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Ascendis Pharma A/S</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>
        The purpose of this trial is to evaluate the safety and efficacy of TransCon TLR7/8 Agonist,&#xD;
        TransCon IL-2 β/γ, and pembrolizumab given prior to curative intent surgery in treatment of&#xD;
        participants with newly diagnosed Stage III/IVA resectable locoregionally advanced head and&#xD;
        neck squamous cell carcinoma (LA-HNSCC). After surgery, participants will receive local&#xD;
        standard-of-care treatment and will be followed for safety, efficacy, and survival for up to&#xD;
        2 years.&#xD;
  &#xD;
        This trial contains a safety run-in to evaluate the safety and tolerability of the two&#xD;
        treatment arms: Arm A (TransCon TLR7/8 Agonist plus pembrolizumab) and Arm B (TransCon TLR7/8&#xD;
        Agonist plus TransCon IL-2 β/γ). The safety run-in will be followed by the randomized Phase&#xD;
        2, open-label part of the trial comparing the safety, efficacy and survival of treatment Arm&#xD;
        A or Arm B compared to treatment Arm C (pembrolizumab monotherapy).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized, Phase 2, open-label, multicenter trial of TransCon TLR7/8 Agonist in&#xD;
        combination with pembrolizumab, TransCon TLR7/8 Agonist in combination with TransCon IL-2&#xD;
        β/γ, or pembrolizumab monotherapy as neoadjuvant therapy in participants with Stage III-IVA&#xD;
        resectable LA-HNSCC.&#xD;
  &#xD;
        This trial starts with a safety run-in of 12 participants, 6 participants each in Arms A&#xD;
        (TransCon TLR7/8 Agonist plus pembrolizumab) and B (TransCon TLR7/8 Agonist plus TransCon&#xD;
        IL-2 β/γ) randomized 1:1.&#xD;
  &#xD;
        After completing the safety run-in, 80 participants will be randomized in a 2:2:1 ratio in 3&#xD;
        treatment Arms A, B or C (pembrolizumab monotherapy).&#xD;
  &#xD;
        Once randomized, participants should begin treatment within 5 calendar days. Participants&#xD;
        enrolled after the safety run-in, into the 2:2:1 randomization part of the trial, will be&#xD;
        stratified as follows: oropharyngeal HPV p16 positive versus oropharyngeal HPV p16 negative&#xD;
        or larynx/hypopharyngeal/oral cavity regardless of HPV p16 status. All participants should&#xD;
        receive study drug(s) every 21 days (Q21D) for 2 cycles followed by curative-intent surgery.&#xD;
        After surgery, participants may receive standard-of-care treatment in the adjuvant setting,&#xD;
        as per investigator's decision and local guidelines.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">August 31, 2023</start_date>
    <completion_date type="Anticipated">July 30, 2027</completion_date>
    <primary_completion_date type="Anticipated">April 14, 2025</primary_completion_date>
    <phase>Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Major Pathological Response</measure>
      <time_frame>Up to 6 weeks after Cycle 2 (each cycle is 21 days)</time_frame>
      <description>The proportion of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Pathological Complete Response</measure>
      <time_frame>Up to 6 weeks after Cycle 2 (each cycle is 21 days)</time_frame>
      <description>A central pathology laboratory and local hospital pathologist will evaluate if all the tumor is completely gone from the primary tumor and all the lymph nodes that were removed at surgery.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Event Free Survival</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>The time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence determined by radiology scans or tumor biopsy as needed, or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Overall Survival</measure>
      <time_frame>Up to 5 years</time_frame>
      <description>The time from randomization to death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Safety and Tolerability</measure>
      <time_frame>From time of signing of the ICF up to 100 (±7) days following the last dose of study drug</time_frame>
      <description>Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).</description>
    </secondary_outcome>
    <number_of_arms>3</number_of_arms>
    <enrollment type="Anticipated">92</enrollment>
    <condition>Head and Neck Neoplasms</condition>
    <arm_group>
      <arm_group_label>TransCon TLR7/8 Agonist in combination with pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants receive 2 cycles, once every 3 weeks of TransCon TLR7/8 Agonist intratumoral (IT) injection in combination with pembrolizumab as a 30-minute intravenous (IV) infusion</description>
    </arm_group>
    <arm_group>
      <arm_group_label>TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants receive 2 cycles, once every 3 weeks of TransCon TLR7/8 Agonist (IT injection) in combination with TransCon IL-2 β/γ as a 30-minute IV infusion</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Pembrolizumab</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Participants receive 2 cycles, once every 3 weeks of pembrolizumab alone as a 30-minute IV infusion</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TransCon TLR7/8 Agonist</intervention_name>
      <description>TLR7/8 agonist prodrug</description>
      <arm_group_label>TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ</arm_group_label>
      <arm_group_label>TransCon TLR7/8 Agonist in combination with pembrolizumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer cells from hiding</description>
      <arm_group_label>Pembrolizumab</arm_group_label>
      <arm_group_label>TransCon TLR7/8 Agonist in combination with pembrolizumab</arm_group_label>
      <other_name>Keytruda™</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>TransCon IL-2 β/γ</intervention_name>
      <description>Sustained systemic release of IL-2 β/γ with selective receptor binding that may stimulate the immune system to kill cancer cells</description>
      <arm_group_label>TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Has local histologically confirmed new diagnosis of resectable, non-metastatic, SCC&#xD;
               that is either: Stage III tumor HPV-positive oropharyngeal primary that is tumor size&#xD;
               (T) 4, lymph node involvement (N) 0-2, no distant metastases (M) 0; Stage III or IVA&#xD;
               oropharyngeal tumor HPV-negative; or Stage III or IVA larynx/hypopharynx/oral cavity&#xD;
               primaries regardless of HPV status (per American Joint Committee on Cancer [AJCC]&#xD;
               Staging, 8th edition).&#xD;
  &#xD;
            -  Has available archived or fresh core or excisional biopsy of a tumor lesion. Note:&#xD;
               Fine needle aspirations may be allowed after discussion with Medical Monitor.&#xD;
  &#xD;
            -  Is eligible and plans for primary LA-HNSCC surgery based on investigator decision and&#xD;
               per local practice.&#xD;
  &#xD;
            -  Has results from tumor HPV status by p16 immunohistochemistry (IHC) for oropharyngeal&#xD;
               tumors. (HPV DNA analysis for HPV tumor status is acceptable if that is the local&#xD;
               standard of care analysis.)&#xD;
  &#xD;
            -  Has adequate organ function at screening.&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.&#xD;
  &#xD;
            -  Has at least one lesion that is deemed by the investigator to be easily and safely&#xD;
               accessible for IT injection.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Active autoimmune conditions.&#xD;
  &#xD;
            -  Has significant cardiac disease.&#xD;
  &#xD;
            -  Has a known bleeding disorder that is deemed to place the participant at unacceptable&#xD;
               risk for bleeding complications from IT injections or biopsies.&#xD;
  &#xD;
            -  Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in doses&#xD;
               exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive&#xD;
               therapy within 7 days prior to randomization.&#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>Joan Morris</last_name>
      <role>Study Director</role>
      <affiliation>Ascendis Pharma Oncology Division A/S</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Margaret Rushing</last_name>
      <phone>+1 650-512-9048</phone>
      <email>MRG@ascendispharma.com</email>
    </overall_contact>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>August 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 8, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>HNSCC</keyword>
    <keyword>Head and Neck Cancer</keyword>
    <keyword>TransCon TLR7/8 Agonist</keyword>
    <keyword>TC TLR7/8</keyword>
    <keyword>TransCon IL-2 β/γ</keyword>
    <keyword>TC IL-2 β/γ</keyword>
    <keyword>Neoadjuvant</keyword>
    <keyword>Neoadjuvant Head and Neck</keyword>
    <keyword>LA-HNSCC</keyword>
    <keyword>Locoregionally Advanced HNSCC</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Carcinoma, Squamous Cell</mesh_term>
      <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
      <mesh_term>Head and Neck Neoplasms</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/NCT05980598
  org study id: ASND0038
  nct id: NCT05980598
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  The purpose of this trial is to evaluate the safety and efficacy of TransCon TLR7/8 Agonist,
        TransCon IL-2 β/γ, and pembrolizumab given prior to curative intent surgery in treatment of
        participants with newly diagnosed Stage III/IVA resectable locoregionally advanced head and
        neck squamous cell carcinoma (LA-HNSCC). After surgery, participants will receive local
        standard-of-care treatment and will be followed for safety, efficacy, and survival for up to
        2 years.
  
        This trial contains a safety run-in to evaluate the safety and tolerability of the two
        treatment arms: Arm A (TransCon TLR7/8 Agonist plus pembrolizumab) and Arm B (TransCon TLR7/8
        Agonist plus TransCon IL-2 β/γ). The safety run-in will be followed by the randomized Phase
        2, open-label part of the trial comparing the safety, efficacy and survival of treatment Arm
        A or Arm B compared to treatment Arm C (pembrolizumab monotherapy).
  This is a randomized, Phase 2, open-label, multicenter trial of TransCon TLR7/8 Agonist in
        combination with pembrolizumab, TransCon TLR7/8 Agonist in combination with TransCon IL-2
        β/γ, or pembrolizumab monotherapy as neoadjuvant therapy in participants with Stage III-IVA
        resectable LA-HNSCC.
  
        This trial starts with a safety run-in of 12 participants, 6 participants each in Arms A
        (TransCon TLR7/8 Agonist plus pembrolizumab) and B (TransCon TLR7/8 Agonist plus TransCon
        IL-2 β/γ) randomized 1:1.
  
        After completing the safety run-in, 80 participants will be randomized in a 2:2:1 ratio in 3
        treatment Arms A, B or C (pembrolizumab monotherapy).
  
        Once randomized, participants should begin treatment within 5 calendar days. Participants
        enrolled after the safety run-in, into the 2:2:1 randomization part of the trial, will be
        stratified as follows: oropharyngeal HPV p16 positive versus oropharyngeal HPV p16 negative
        or larynx/hypopharyngeal/oral cavity regardless of HPV p16 status. All participants should
        receive study drug(s) every 21 days (Q21D) for 2 cycles followed by curative-intent surgery.
        After surgery, participants may receive standard-of-care treatment in the adjuvant setting,
        as per investigator's decision and local guidelines.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Major Pathological Response
  time frame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
  description: The proportion of participants with a major pathological response (mPR) as assessed by the Central Pathologist at the time of definitive surgery. mPR is defined as ≤10% invasive squamous cell carcinoma within the resected primary tumor specimen and all the sampled regional lymph nodes.
  measure: Pathological Complete Response
  time frame: Up to 6 weeks after Cycle 2 (each cycle is 21 days)
  description: A central pathology laboratory and local hospital pathologist will evaluate if all the tumor is completely gone from the primary tumor and all the lymph nodes that were removed at surgery.
  measure: Event Free Survival
  time frame: Up to 5 years
  description: The time from the date of randomization to the date of first record of any of the following events: disease progression; local or distant recurrence determined by radiology scans or tumor biopsy as needed, or death due to any cause.
  measure: Overall Survival
  time frame: Up to 5 years
  description: The time from randomization to death due to any cause.
  measure: Safety and Tolerability
  time frame: From time of signing of the ICF up to 100 (±7) days following the last dose of study drug
  description: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs).
  arm group label: TransCon TLR7/8 Agonist in combination with pembrolizumab
  arm group type: Experimental
  description: Participants receive 2 cycles, once every 3 weeks of TransCon TLR7/8 Agonist intratumoral (IT) injection in combination with pembrolizumab as a 30-minute intravenous (IV) infusion
  arm group label: TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
  arm group type: Experimental
  description: Participants receive 2 cycles, once every 3 weeks of TransCon TLR7/8 Agonist (IT injection) in combination with TransCon IL-2 β/γ as a 30-minute IV infusion
  arm group label: Pembrolizumab
  arm group type: Active Comparator
  description: Participants receive 2 cycles, once every 3 weeks of pembrolizumab alone as a 30-minute IV infusion
  intervention type: Drug
  intervention name: TransCon TLR7/8 Agonist
  description: TLR7/8 agonist prodrug
  arm group label: TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
  arm group label: TransCon TLR7/8 Agonist in combination with pembrolizumab
  intervention type: Drug
  intervention name: Pembrolizumab
  description: A type of immunotherapy that works by blocking the PD-1 pathway to help prevent cancer cells from hiding
  arm group label: Pembrolizumab
  arm group label: TransCon TLR7/8 Agonist in combination with pembrolizumab
  other name: Keytruda™
  intervention type: Drug
  intervention name: TransCon IL-2 β/γ
  description: Sustained systemic release of IL-2 β/γ with selective receptor binding that may stimulate the immune system to kill cancer cells
  arm group label: TransCon TLR7/8 Agonist in combination with TransCon IL-2 β/γ
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Joan Morris
  role: Study Director
  affiliation: Ascendis Pharma Oncology Division A/S
  last name: Margaret Rushing
  phone: +1 650-512-9048
  email: MRG@ascendispharma.com
  responsible party type: Sponsor
  mesh term: Carcinoma, Squamous Cell
  mesh term: Squamous Cell Carcinoma of Head and Neck
  mesh term: Head and Neck Neoplasms
  mesh term: Pembrolizumab
  sharing ipd: No