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/NCT06016920</url>
    </required_header>
    <id_info>
      <org_study_id>VB-C-03</org_study_id>
      <secondary_id>2022-503055-26-00</secondary_id>
      <secondary_id>KEYNOTE-E72</secondary_id>
      <nct_id>NCT06016920</nct_id>
    </id_info>
    <brief_title>Safety and Efficacy of VB10.16 and Pembrolizumab in Patients With Head-Neck Squamous Cell Carcinoma</brief_title>
    <official_title>A Phase 1/2a, Open-label, Dose-finding Trial to Evaluate Safety, Immunogenicity, and Anti-tumor Activity of VB10.16 and Pembrolizumab in Patients With Unresectable Recurrent or Metastatic HPV16-positive Head-Neck Squamous Cell Carcinoma</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Nykode Therapeutics ASA</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Merck Sharp &amp; Dohme LLC</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>Nykode Therapeutics ASA</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This is a multi-center study in patients with un-resectable Recurrent or Metastatic&#xD;
        HPV16-positive Head and Neck Squamous Cell Carcinoma (HNSCC). The trial is designed to&#xD;
        investigate VB10.16, an investigational therapeutic DNA vaccine in combination with another&#xD;
        medicine, pembrolizumab, which is the standard of care for patients with previously untreated&#xD;
        metastatic or resectable recurrent PD-L1 positive HNSCC. The study is divided in 2 parts: a&#xD;
        phase 1, dose escalation part, testing 3 different doses of VB10.16 in combination with a&#xD;
        standard fixed dose of pembrolizumab. The goal of this part is to evaluate the safety and&#xD;
        tolerability of the combined treatment and to decide on the dose of VB10.16 to be used in the&#xD;
        second part of the trial. In the second part of the trial, a phase 2a, dose expansion part,&#xD;
        participants will receive either the highest safe dose of VB10.16 from part 1 or the 3 mg&#xD;
        dose both in combination with pembrolizumab. The dose given to each participant will be&#xD;
        decided in random.&#xD;
  &#xD;
        The trial is designed to define the optimal dose of VB10.16 in combination with pembrolizumab&#xD;
        for future clinical studies based on the safety, tolerability and anti-tumor effect data&#xD;
        generated.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This phase 1/2a, open-label, dose-finding trial is designed to evaluate the safety,&#xD;
        tolerability, immunogenicity, and anti-tumor activity of VB10.16 immunotherapy in patients&#xD;
        with HPV16-positive R/M HNSCC whose tumors express PDL1 (CPS ≥ 1) and who are eligible for&#xD;
        pembrolizumab monotherapy as standard of care. The trial is designed to determine the&#xD;
        biological optimal dose (BOD) of VB10.16 in combination with a fixed dose of pembrolizumab&#xD;
        based on the totality of data (i.e., safety, tolerability, anti-tumor activity, and HPV16&#xD;
        E6/E7specific cellular immune response). The trial consists of 2 consecutive phases with&#xD;
        separate patient groups in a seamless trial design: a dose escalation phase (phase 1) and a&#xD;
        dose expansion phase (phase 2a). After completing 48 weeks of combination treatment, patients&#xD;
        can either continue pembrolizumab treatment with 200 mg Q3W administration or change to 400&#xD;
        mg Q6W administration at the discretion of the investigator and after consultation with the&#xD;
        Sponsor.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">January 2028</completion_date>
    <primary_completion_date type="Anticipated">September 2027</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Sequential Assignment</intervention_model>
      <intervention_model_description>Dose-finding trial, including a dose escalation phase (phase 1) where participants are allocated sequentially to one of the 3 escalating doses; and a dose expansion phase (phase 2a) where participants are randomized to one of two doses</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)</measure>
      <time_frame>42 days</time_frame>
      <description>Proportion of patient with Dose Limiting Toxicities (DLTs).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 2: Dose Expansion: AEs</measure>
      <time_frame>50 Weeks</time_frame>
      <description>Proportion of patients with AEs following treatment initiation by severity grade.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 2: Dose Expansion: Discontinuation due to adverse reaction</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients who discontinue due to an adverse reaction.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 2: Dose Expansion: Objective Response Rate (ORR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 2: Dose Expansion: Immune response</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients with increased HPV16 E6/E7-specific cellular immune responses from baseline as measured by E6/E7-IFN-γ ELISpot in post-vaccination samples.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Objective Response Rate (ORR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response (BOR) per RECIST 1.1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Objective Response Rate (ORR)</measure>
      <time_frame>103 weeks</time_frame>
      <description>Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Duration of response (DOR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Duration of response (DOR)</measure>
      <time_frame>103 weeks</time_frame>
      <description>Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Progression-free survival (PFS)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Progression-free survival (PFS)</measure>
      <time_frame>103 weeks</time_frame>
      <description>Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Proportion Progression-free</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients who progression-free and alive.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1+2: Full trial: Proportion Progression-free</measure>
      <time_frame>103 weeks</time_frame>
      <description>Proportion of patients who are progression-free and alive.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1 + 2: Full trial: Overall survival (OS)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1 + 2: Full trial: Overall survival (OS)</measure>
      <time_frame>103 weeks</time_frame>
      <description>Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1 + 2: Full trial: Proportion alive</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients who are alive.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Phase 1 + 2: Full trial: Proportion alive</measure>
      <time_frame>103 weeks</time_frame>
      <description>Proportion of patients who are alive.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Disease control rate (DCR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Disease control rate (DCR), defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as BOR according to RECIST 1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Duration of response (DOR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Duration of complete response (DOCR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Duration of complete response (DOCR), defined as time from the date of first documented response of CR to the date of the first documented progression or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Duration of Disease Control (DODC)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Duration of Disease Control (DODC), defined as time from the date of first documented response of CR, PR or SD to the date of the first documented progression or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Time to Response (TTR)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Time to Response (TTR), s defined as the time from VB10.16 treatment start date to the date of first documented response of either confirmed CR or confirmed PR.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Progression-free survival (PFS)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Dose Expansion: Overall Survival (OS)</measure>
      <time_frame>50 weeks</time_frame>
      <description>Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Proportion of progression-free</measure>
      <time_frame>26 weeks</time_frame>
      <description>Proportion of patients who are progression-free and alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Proportion of progression-free</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients who are progression-free and alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Patients alive</measure>
      <time_frame>26 weeks</time_frame>
      <description>Proportion of patients who are alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 2: Patients alive</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients who are alive.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 1+2: Full trial: AEs following treatment initiation</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients with AEs following treatment initiation by severity grade.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 1+2: Full trial: AEs following treatment initiation</measure>
      <time_frame>103 weeks</time_frame>
      <description>Proportion of patients with AEs following treatment initiation by severity grade.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 1+2: Discontinuation due to an adverse reaction</measure>
      <time_frame>50 weeks</time_frame>
      <description>Proportion of patients who discontinue due to an adverse reaction.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Phase 1+2: Discontinuation due to an adverse reaction</measure>
      <time_frame>103 weeks</time_frame>
      <description>Proportion of patients who discontinue due to an adverse reaction.</description>
    </secondary_outcome>
    <number_of_arms>5</number_of_arms>
    <enrollment type="Anticipated">51</enrollment>
    <condition>HPV-Related Squamous Cell Carcinoma</condition>
    <condition>HNSCC</condition>
    <arm_group>
      <arm_group_label>Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles&#xD;
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>6 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps or gluteus muscles&#xD;
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>9 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle&#xD;
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>The highest dose of VB10.16 to be safety-cleared in the escalation phase will be given via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle&#xD;
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles&#xD;
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>VB10.16</intervention_name>
      <description>Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) starting at Week 1/Day 1 during a 12-week induction period, followed by a maintenance period with administrations every 6 weeks (Q6W) from Week 13 until Week 48. A total of up to 10 i.m. administrations will be given.&#xD;
  VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.</description>
      <arm_group_label>Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Pembrolizumab</intervention_name>
      <description>Pembrolizumab 200 mg intravenous (i.v.) will be given in accordance with the local regulatory-approved label Q3W starting at Week 1/Day 1 for as long as the patient tolerates and continues to have clinical benefit from the treatment based on the patient and investigator's decision, up to a maximum of 35 treatments corresponding to approximately 2 years of treatment.&#xD;
  After 48 weeks of treatment patients can continue on 200 mg Q3W or change to 400 mg Q6W at the discretion of the investigator and after consultation with the sponsor.&#xD;
  Pembrolizumab will be given by i.v. infusion over 30 minutes.</description>
      <arm_group_label>Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab</arm_group_label>
      <arm_group_label>Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab</arm_group_label>
      <other_name>KEYTRUDA</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
          GENERAL REQUIREMENTS&#xD;
  &#xD;
            1. ≥18 years of age (or as per national legal age of trial consent, whichever is higher)&#xD;
               at date of signing the informed consent form (ICF)&#xD;
  &#xD;
            2. Histologically or cytologically confirmed R/M HNSCC considered incurable by local&#xD;
               therapy and eligible for monotherapy with pembrolizumab&#xD;
  &#xD;
            3. HPV16 positivity of R/M HNSCC confirmed by designated central laboratory&#xD;
  &#xD;
            4. PD-L1 positivity (CPS ≥1)&#xD;
  &#xD;
            5. Must provide a tumor tissue sample collected prior to VB10.16 treatment initiation for&#xD;
               baseline tumor microenvironment analyses&#xD;
  &#xD;
            6. Primary tumor location in the oropharynx, oral cavity, hypopharynx, or larynx&#xD;
  &#xD;
            7. At least 1 measurable lesion per RECIST 1.1&#xD;
  &#xD;
               ORGAN FUNCTION&#xD;
  &#xD;
               Overall function:&#xD;
  &#xD;
            8. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 1&#xD;
  &#xD;
               Hematological function:&#xD;
  &#xD;
            9. Platelets 100 - 400 × 10^9/L (100,000 - 400,000/µL)&#xD;
  &#xD;
           10. Neutrophils (absolute neutrophil count [ANC]) ≥1.5 × 10^9/L (1,500/µL)&#xD;
  &#xD;
           11. Hemoglobin ≥5.6 mmol/L (9.0 g/dL)&#xD;
  &#xD;
               Hepatic and hemostatic function:&#xD;
  &#xD;
           12. Bilirubin (BILI), total ≤1.5 × upper limit of normal (ULN) (except Gilbert syndrome,&#xD;
               then direct BILI ≤2 × ULN)&#xD;
  &#xD;
           13. Aspartate transaminase (AST) ≤ 2.5 × ULN&#xD;
  &#xD;
           14. Alanine transaminase (ALT) ≤ 2.5 × ULN&#xD;
  &#xD;
           15. Alkaline phosphatase ≤ 2.5 × ULN&#xD;
  &#xD;
           16. International normalized ratio (INR) ≤1.5 × ULN&#xD;
  &#xD;
               Renal function:&#xD;
  &#xD;
           17. Estimated glomerular filtration rate (eGFR) ≥45 mL/min/1.73 m^2 using the&#xD;
               Cockroft-Gault formula&#xD;
  &#xD;
               OTHER TRIAL REQUIREMENTS&#xD;
  &#xD;
           18. Female patients of childbearing potential: negative serum pregnancy test (≤72 hours)&#xD;
  &#xD;
           19. Female patients of childbearing potential and male patients must agree to use highly&#xD;
               effective contraception, and male patients must refrain from sperm donation throughout&#xD;
               the trial (14 days prior to initiation of treatment for oral contraception), and for&#xD;
               at least 120 days (according to the latest country-specific pembrolizumab label) after&#xD;
               the last dose of pembrolizumab and up to 6 months after the last dose of VB10.16,&#xD;
               whichever comes last&#xD;
  &#xD;
           20. Patients capable of giving informed consent must provide signed and dated written&#xD;
               informed consent prior to initiation of any study-related procedures.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
          HNSCC DISEASE&#xD;
  &#xD;
            1. Has disease that is suitable for local therapy with curative intent&#xD;
  &#xD;
            2. Has progressive disease ≤6 months after completion of curatively intended systemic&#xD;
               treatment for locoregionally advanced R/M HNSCC&#xD;
  &#xD;
            3. Primary tumor site of the nasopharynx (any histology)&#xD;
  &#xD;
            4. Rapidly progressing disease (e.g., tumor bleeding, uncontrolled tumor pain) in the&#xD;
               opinion of the investigator&#xD;
  &#xD;
               PRIOR, CONCURRENT, OR FUTURE INTERVENTIONS&#xD;
  &#xD;
            5. Has received prior radiotherapy within 2 weeks of start of trial treatment or has had&#xD;
               a history of radiation pneumonitis&#xD;
  &#xD;
            6. Any prior investigational or approved systemic antineoplastic drug or invasive medical&#xD;
               device (including ICIs), either as monotherapy or as part of a combination regimen&#xD;
               administered in the R/M HNSCC setting&#xD;
  &#xD;
            7. Prior solid organ or tissue transplantation (except corneal transplant)&#xD;
  &#xD;
            8. Prior autologous or allogeneic hematopoietic stem cell transplantation (HSCT)&#xD;
  &#xD;
            9. Prior chimeric antigen receptor T (CAR-T) cell therapy&#xD;
  &#xD;
           10. Prior therapy with a monoclonal or bispecific antibody or antibody fragment (or other&#xD;
               molecule with similar mechanism of action) that engages T-cells&#xD;
  &#xD;
           11. Has received a live or live-attenuated vaccine within 30 days prior to the first dose&#xD;
               of trial intervention&#xD;
  &#xD;
           12. Administration of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine&#xD;
               within 30 days prior to VB10.16 treatment start&#xD;
  &#xD;
           13. Prior administration with a therapeutic HPV16 vaccine&#xD;
  &#xD;
           14. Patients receiving systemic immunosuppression with immunosuppressive agents such as&#xD;
               cyclosporine, azathioprine, methotrexate, or tumor necrosis factor alpha (TNF α)&#xD;
               blockers for any concurrent condition&#xD;
  &#xD;
           15. Chronic administration of systemic corticosteroids: prednisone &gt;10 mg daily (or dose&#xD;
               equivalent) or an average cumulative dose of &gt;140 mg prednisone (or dose equivalent)&#xD;
               within the last 14 consecutive days prior to VB10.16 treatment start&#xD;
  &#xD;
           16. Administration of G-CSF/GM-CSF or transfusions with red blood cells, platelets, or&#xD;
               plasma components ≤2 weeks prior to VB10.16 treatment start&#xD;
  &#xD;
           17. 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 (e.g.,&#xD;
               CTLA-4, OX 40, CD137)&#xD;
  &#xD;
           18. Has received prior surgery or prior systemic anti-cancer therapy including&#xD;
               investigational agents within 4 weeks prior to treatment&#xD;
  &#xD;
           19. Any planned major surgery&#xD;
  &#xD;
               PRIOR OR CONCURRENT MORBIDITY&#xD;
  &#xD;
               Malignancy:&#xD;
  &#xD;
           20. Past or current malignancy other than inclusion diagnosis, except for:&#xD;
  &#xD;
                 -  Cervical carcinoma, stage 1B or less&#xD;
  &#xD;
                 -  Noninvasive basal cell or squamous cell skin carcinoma&#xD;
  &#xD;
                 -  Noninvasive, superficial bladder cancer&#xD;
  &#xD;
                 -  Prostate cancer with a current prostate-specific antigen level &lt;0.1 ng/mL&#xD;
  &#xD;
                 -  Any curable cancer with a complete response of &gt;2 years' duration&#xD;
  &#xD;
               Hepatic and hemostatic function:&#xD;
  &#xD;
           21. Any current bleeding disorder, active bleeding, or bleeding diathesis&#xD;
  &#xD;
               Cardiovascular function:&#xD;
  &#xD;
           22. Symptomatic congestive heart failure (Grade III or IV as classified by the New York&#xD;
               Heart Association), unstable angina pectoris, or cardiac arrhythmia&#xD;
  &#xD;
           23. History of myocardial infarction ≤ 6 months prior to planned VB10.16 treatment start&#xD;
  &#xD;
           24. Uncontrolled hypertension (systolic blood pressure ≥160 mmHg and/or diastolic blood&#xD;
               pressure ≥100 mmHg), despite optimal medical management&#xD;
  &#xD;
           25. Any other significant cardiac disease(s) that, in the opinion of the investigator,&#xD;
               is/are clinically significant and/or unacceptable&#xD;
  &#xD;
               Pulmonary function:&#xD;
  &#xD;
           26. Has a history of (non-infectious) pneumonitis / interstitial lung disease that&#xD;
               required steroids or has current pneumonitis / interstitial lung disease&#xD;
  &#xD;
               Immune system and infectious diseases:&#xD;
  &#xD;
           27. Primary immunodeficiency, other immunosuppressive disorder, and/or other causes of&#xD;
               immunosuppression&#xD;
  &#xD;
           28. Has an active autoimmune disease that has required systemic treatment in the past 2&#xD;
               years (i.e., with use of disease-modifying agents, corticosteroids, or&#xD;
               immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or&#xD;
               physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)&#xD;
               is not considered a form of systemic treatment and is allowed&#xD;
  &#xD;
           29. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is&#xD;
               required unless mandated by a local health authority&#xD;
  &#xD;
           30. Has a known history of Hepatitis B (defined as HBsAg reactive) or known active&#xD;
               Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection&#xD;
  &#xD;
           31. Any active, acute, or chronic infection that is uncontrolled and/or requires systemic&#xD;
               treatment&#xD;
  &#xD;
           32. Known allergies, sensitivity, or intolerance to drug excipients, or aminoglycosides&#xD;
               (especially kanamycin).&#xD;
  &#xD;
               Central nervous system (CNS) function:&#xD;
  &#xD;
           33. Any history of intracerebral arteriovenous malformations, cerebral aneurysm, or stroke&#xD;
  &#xD;
           34. Has known active CNS metastases and/or carcinomatous meningitis. Patients 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;
               (note that the repeat imaging should be performed during trial screening), clinically&#xD;
               stable and without requirement of steroid treatment for at least 14 days prior to&#xD;
               first dose of trial treatment&#xD;
  &#xD;
           35. New (≤6 months), progressive and/or symptomatic brain metastases&#xD;
  &#xD;
               OTHER&#xD;
  &#xD;
           36. Is currently participating in or has participated in a trial of an investigational&#xD;
               agent or has used an investigational device within 4 weeks prior to the first dose of&#xD;
               trial treatment&#xD;
  &#xD;
           37. Has a history or current evidence of any condition, therapy, or laboratory&#xD;
               abnormality, or other circumstance that might confound the results of the trial or&#xD;
               interfere with the patient's participation for the full duration of the trial, such&#xD;
               that it is not in the best interest of the patient to participate, in the opinion of&#xD;
               the treating investigator&#xD;
  &#xD;
           38. Has a known psychiatric or substance abuse disorder that would interfere with the&#xD;
               patient's ability to cooperate with the requirements of the trial&#xD;
  &#xD;
           39. Has a concomitant medical condition requiring receipt of a therapeutic anticoagulant&#xD;
               that, in the opinion of the treating physician, would contraindicate administration of&#xD;
               VB10.16 and tumor biopsies&#xD;
  &#xD;
           40. Female patients who are pregnant or breastfeeding&#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>Åse Bratland, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Oslo University Hospital</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Chief Medical Officer</last_name>
      <phone>+47 951 133 93</phone>
      <email>storhaug@nykode.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Senior Clinical Trial Manager</last_name>
      <phone>+47 970 695 95</phone>
      <email>lfinnesand@nykode.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>East and North Hertfordshire NHS Trust Mount Vernon Hospital</name>
        <address>
          <city>London</city>
          <country>United Kingdom</country>
        </address>
      </facility>
      <contact>
        <last_name>Saira Khalique, Dr</last_name>
      </contact>
    </location>
    <location_countries>
      <country>United Kingdom</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 24, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>August 24, 2023</last_update_submitted>
    <last_update_submitted_qc>August 24, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 30, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Unresectable</keyword>
    <keyword>recurrent</keyword>
    <keyword>metastatic</keyword>
    <keyword>HPV16 positive</keyword>
    <keyword>PD-L1</keyword>
    <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>
    </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/NCT06016920
  org study id: VB-C-03
  secondary id: 2022-503055-26-00
  secondary id: KEYNOTE-E72
  nct id: NCT06016920
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This is a multi-center study in patients with un-resectable Recurrent or Metastatic
        HPV16-positive Head and Neck Squamous Cell Carcinoma (HNSCC). The trial is designed to
        investigate VB10.16, an investigational therapeutic DNA vaccine in combination with another
        medicine, pembrolizumab, which is the standard of care for patients with previously untreated
        metastatic or resectable recurrent PD-L1 positive HNSCC. The study is divided in 2 parts: a
        phase 1, dose escalation part, testing 3 different doses of VB10.16 in combination with a
        standard fixed dose of pembrolizumab. The goal of this part is to evaluate the safety and
        tolerability of the combined treatment and to decide on the dose of VB10.16 to be used in the
        second part of the trial. In the second part of the trial, a phase 2a, dose expansion part,
        participants will receive either the highest safe dose of VB10.16 from part 1 or the 3 mg
        dose both in combination with pembrolizumab. The dose given to each participant will be
        decided in random.
  
        The trial is designed to define the optimal dose of VB10.16 in combination with pembrolizumab
        for future clinical studies based on the safety, tolerability and anti-tumor effect data
        generated.
  This phase 1/2a, open-label, dose-finding trial is designed to evaluate the safety,
        tolerability, immunogenicity, and anti-tumor activity of VB10.16 immunotherapy in patients
        with HPV16-positive R/M HNSCC whose tumors express PDL1 (CPS ≥ 1) and who are eligible for
        pembrolizumab monotherapy as standard of care. The trial is designed to determine the
        biological optimal dose (BOD) of VB10.16 in combination with a fixed dose of pembrolizumab
        based on the totality of data (i.e., safety, tolerability, anti-tumor activity, and HPV16
        E6/E7specific cellular immune response). The trial consists of 2 consecutive phases with
        separate patient groups in a seamless trial design: a dose escalation phase (phase 1) and a
        dose expansion phase (phase 2a). After completing 48 weeks of combination treatment, patients
        can either continue pembrolizumab treatment with 200 mg Q3W administration or change to 400
        mg Q6W administration at the discretion of the investigator and after consultation with the
        Sponsor.
  allocation: Non-Randomized
  intervention model: Sequential Assignment
  intervention model description: Dose-finding trial, including a dose escalation phase (phase 1) where participants are allocated sequentially to one of the 3 escalating doses; and a dose expansion phase (phase 2a) where participants are randomized to one of two doses
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Phase 1: Dose Escalation: Dose Limiting Toxicities (DLT)
  time frame: 42 days
  description: Proportion of patient with Dose Limiting Toxicities (DLTs).
  measure: Phase 2: Dose Expansion: AEs
  time frame: 50 Weeks
  description: Proportion of patients with AEs following treatment initiation by severity grade.
  measure: Phase 2: Dose Expansion: Discontinuation due to adverse reaction
  time frame: 50 weeks
  description: Proportion of patients who discontinue due to an adverse reaction.
  measure: Phase 2: Dose Expansion: Objective Response Rate (ORR)
  time frame: 50 weeks
  description: Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
  measure: Phase 2: Dose Expansion: Immune response
  time frame: 50 weeks
  description: Proportion of patients with increased HPV16 E6/E7-specific cellular immune responses from baseline as measured by E6/E7-IFN-γ ELISpot in post-vaccination samples.
  measure: Phase 1+2: Full trial: Objective Response Rate (ORR)
  time frame: 50 weeks
  description: Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response (BOR) per RECIST 1.1.
  measure: Phase 1+2: Full trial: Objective Response Rate (ORR)
  time frame: 103 weeks
  description: Objective Response Rate (ORR), defined as the proportion of patients who have either confirmed CR or confirmed PR as best overall response per RECIST 1.1.
  measure: Phase 1+2: Full trial: Duration of response (DOR)
  time frame: 50 weeks
  description: Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
  measure: Phase 1+2: Full trial: Duration of response (DOR)
  time frame: 103 weeks
  description: Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
  measure: Phase 1+2: Full trial: Progression-free survival (PFS)
  time frame: 50 weeks
  description: Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
  measure: Phase 1+2: Full trial: Progression-free survival (PFS)
  time frame: 103 weeks
  description: Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
  measure: Phase 1+2: Full trial: Proportion Progression-free
  time frame: 50 weeks
  description: Proportion of patients who progression-free and alive.
  measure: Phase 1+2: Full trial: Proportion Progression-free
  time frame: 103 weeks
  description: Proportion of patients who are progression-free and alive.
  measure: Phase 1 + 2: Full trial: Overall survival (OS)
  time frame: 50 weeks
  description: Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
  measure: Phase 1 + 2: Full trial: Overall survival (OS)
  time frame: 103 weeks
  description: Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
  measure: Phase 1 + 2: Full trial: Proportion alive
  time frame: 50 weeks
  description: Proportion of patients who are alive.
  measure: Phase 1 + 2: Full trial: Proportion alive
  time frame: 103 weeks
  description: Proportion of patients who are alive.
  measure: Phase 2: Dose Expansion: Disease control rate (DCR)
  time frame: 50 weeks
  description: Disease control rate (DCR), defined as the proportion of patients who have either confirmed CR, confirmed PR, or SD as BOR according to RECIST 1.1.
  measure: Phase 2: Dose Expansion: Duration of response (DOR)
  time frame: 50 weeks
  description: Duration of response (DOR), defined as time from the date of first documented response of CR or PR to the date of the first documented progression or death due to any cause.
  measure: Phase 2: Dose Expansion: Duration of complete response (DOCR)
  time frame: 50 weeks
  description: Duration of complete response (DOCR), defined as time from the date of first documented response of CR to the date of the first documented progression or death due to any cause.
  measure: Phase 2: Dose Expansion: Duration of Disease Control (DODC)
  time frame: 50 weeks
  description: Duration of Disease Control (DODC), defined as time from the date of first documented response of CR, PR or SD to the date of the first documented progression or death due to any cause.
  measure: Phase 2: Dose Expansion: Time to Response (TTR)
  time frame: 50 weeks
  description: Time to Response (TTR), s defined as the time from VB10.16 treatment start date to the date of first documented response of either confirmed CR or confirmed PR.
  measure: Phase 2: Dose Expansion: Progression-free survival (PFS)
  time frame: 50 weeks
  description: Progression-free survival (PFS), defined as the time from the VB10.16 treatment start date to the date of the first documented progression or death from any cause, whichever occurs first.
  measure: Phase 2: Dose Expansion: Overall Survival (OS)
  time frame: 50 weeks
  description: Overall survival (OS), defined as the time from VB10.16 treatment start date to the date of death from any cause.
  measure: Phase 2: Proportion of progression-free
  time frame: 26 weeks
  description: Proportion of patients who are progression-free and alive.
  measure: Phase 2: Proportion of progression-free
  time frame: 50 weeks
  description: Proportion of patients who are progression-free and alive.
  measure: Phase 2: Patients alive
  time frame: 26 weeks
  description: Proportion of patients who are alive.
  measure: Phase 2: Patients alive
  time frame: 50 weeks
  description: Proportion of patients who are alive.
  measure: Phase 1+2: Full trial: AEs following treatment initiation
  time frame: 50 weeks
  description: Proportion of patients with AEs following treatment initiation by severity grade.
  measure: Phase 1+2: Full trial: AEs following treatment initiation
  time frame: 103 weeks
  description: Proportion of patients with AEs following treatment initiation by severity grade.
  measure: Phase 1+2: Discontinuation due to an adverse reaction
  time frame: 50 weeks
  description: Proportion of patients who discontinue due to an adverse reaction.
  measure: Phase 1+2: Discontinuation due to an adverse reaction
  time frame: 103 weeks
  description: Proportion of patients who discontinue due to an adverse reaction.
  arm group label: Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab
  arm group type: Experimental
  description: 3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
  arm group label: Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab
  arm group type: Experimental
  description: 6 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps or gluteus muscles
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
  arm group label: Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab
  arm group type: Experimental
  description: 9 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
  arm group label: Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab
  arm group type: Experimental
  description: The highest dose of VB10.16 to be safety-cleared in the escalation phase will be given via i.m. needle-free injections in the deltoid muscles and quadriceps and/or gluteus muscle
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
  arm group label: Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab
  arm group type: Experimental
  description: 3 mg of VB10.16 via i.m. needle-free injections in the deltoid muscles
  Pembrolizumab will be given as standard of care/ background medication via i.v. infusions
  intervention type: Biological
  intervention name: VB10.16
  description: Intramuscular (i.m.) administrations of VB10.16 every 3 weeks (Q3W) starting at Week 1/Day 1 during a 12-week induction period, followed by a maintenance period with administrations every 6 weeks (Q6W) from Week 13 until Week 48. A total of up to 10 i.m. administrations will be given.
  VB10.16 will be administered via Pharma Jet® Stratis 0.5 mL needle free injection system.
  arm group label: Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab
  arm group label: Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab
  arm group label: Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab
  arm group label: Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab
  arm group label: Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab
  intervention type: Drug
  intervention name: Pembrolizumab
  description: Pembrolizumab 200 mg intravenous (i.v.) will be given in accordance with the local regulatory-approved label Q3W starting at Week 1/Day 1 for as long as the patient tolerates and continues to have clinical benefit from the treatment based on the patient and investigator's decision, up to a maximum of 35 treatments corresponding to approximately 2 years of treatment.
  After 48 weeks of treatment patients can continue on 200 mg Q3W or change to 400 mg Q6W at the discretion of the investigator and after consultation with the sponsor.
  Pembrolizumab will be given by i.v. infusion over 30 minutes.
  arm group label: Phase 1: Dose Escalation: 6 mg VB10.16 + Pembrolizumab
  arm group label: Phase 1: Dose Escalation: 9 mg VB10.16 + Pembrolizumab
  arm group label: Phase 2: Dose Expansion: 3 mg VB10.16 + Pembrolizumab
  arm group label: Phase 2: Dose Expansion: High dose of VB10.16 + Pembrolizumab
  arm group label: Phase1: Dose Escalation: 3 mg VB10.16 + Pembrolizumab
  other name: KEYTRUDA
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Åse Bratland, MD, PhD
  role: Principal Investigator
  affiliation: Oslo University Hospital
  last name: Chief Medical Officer
  phone: +47 951 133 93
  email: storhaug@nykode.com
  last name: Senior Clinical Trial Manager
  phone: +47 970 695 95
  email: lfinnesand@nykode.com
  facility: 
  contact: 
  country: United Kingdom
  responsible party type: Sponsor
  mesh term: Carcinoma
  mesh term: Carcinoma, Squamous Cell
  mesh term: Pembrolizumab
  sharing ipd: No