<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/NCT04405349</url>
  </required_header>
  <id_info>
    <org_study_id>VB C-02</org_study_id>
    <nct_id>NCT04405349</nct_id>
  </id_info>
  <brief_title>Investigating the Combination of VB10.16 and Atezolizumab in Patients With HPV 16-positive Cervical Cancer</brief_title>
  <official_title>A Multi-Centre, Open-label Phase 2a Trial of the Combination of VB10.16 and Atezolizumab in Patients With Advanced or Recurrent, Non-resectable HPV 16-Positive Cervical Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nykode Therapeutics ASA</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Roche Pharma AG</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Vaccibody AS</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 phase IIa study is designed to evaluate the safety and efficacy of multiple dosing with&#xD;
      VB10.16 immunotherapy in combination with atezolizumab in patients with advanced or recurrent&#xD;
      non-resectable HPV16-positive cervical cancer, who failed or are not eligible for current&#xD;
      standard of care.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients will receive up to 11 intramuscular (i.m.) vaccinations of VB10.16, for up to 48&#xD;
      weeks from first vaccination. Patients will receive 5 vaccinations of 3 mg VB10.16 during the&#xD;
      first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks from first&#xD;
      immunisation (total of 11 vaccinations). Patients will receive up to 17 infusions of&#xD;
      atezolizumab for up to 48 weeks from first treatment. Atezolizumab (1200 mg) will be&#xD;
      administered as an intravenous (i.v.) infusion every 3 weeks. A follow-up period of up to 12&#xD;
      months will follow the 48 week treatment period.&#xD;
&#xD;
      Response to the VB10.16 and atezolizumab combination will be assessed by computed tomography&#xD;
      (CT)/magnetic resonance imaging (MRI) at every 9 weeks throughout the treatment period&#xD;
      according to the RECIST 1.1 criteria.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">March 2024</completion_date>
  <primary_completion_date type="Actual">August 4, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of adverse events (AEs)</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>The number and percentage of participants that experience an adverse event (AE</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>ORR as assessed by RECIST v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DOR)</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>Estimate the duration of response (DOR) in patients with advanced cervical cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>Estimate the Progression-free survival (PFS) in patients with advanced cervical cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>Overall survival (OS) in patients with advanced cervical cancer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>Systemic T-cell response</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assess predictive biomarkers, such as programmed death-ligand 1 (PD-L1) in tumour material and investigate changes in tumour microenvironment by immunohistochemistry (IHC) and/or gene expression</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>T cell infiltration, PD-L1 expression or other immune-oncology related genes</description>
  </other_outcome>
  <other_outcome>
    <measure>Correlating HPV16 circulating tumour DNA (ctDNA) in plasma with clinical response using RECIST 1.1</measure>
    <time_frame>48 weeks (1 year follow-up)</time_frame>
    <description>ctDNA</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Cervical Cancer</condition>
  <condition>Cervix Cancer</condition>
  <arm_group>
    <arm_group_label>Combination Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>VB10.16 vaccinations. 11 intramuscular (i.m.) vaccinations for up to 48 weeks from first vaccination. 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks + Atezolizumab (1200 mg) intravenous (i.v.) infusion every 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>VB10.16</intervention_name>
    <description>Vaccination</description>
    <arm_group_label>Combination Therapy</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Atezolizumab</intervention_name>
    <description>Intravenously infusion</description>
    <arm_group_label>Combination Therapy</arm_group_label>
    <other_name>Tecentriq</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Has persistent, recurrent, or metastatic non-resectable squamous cell carcinoma,&#xD;
             adeno-squamous carcinoma, or adenocarcinoma of the cervix, who has failed or is not&#xD;
             eligible for treatment with systemic chemotherapy, radiotherapy or other&#xD;
             standard-of-care anticancer treatment.&#xD;
&#xD;
          2. Tumour must be HPV16 positive. Provision of an archival tumour tissue sample not older&#xD;
             than 2 years or new biopsy for analysing HPV16 status is mandatory.&#xD;
&#xD;
          3. Must have a biopsy (archived or new) available for PD L1 assessment at Screening.&#xD;
&#xD;
          4. Has measurable disease as assessed by the local site investigator/radiology as per&#xD;
             RECIST 1.1.&#xD;
&#xD;
          5. Has recovered from the effects of surgery, radiation therapy, or chemoradiotherapy.&#xD;
&#xD;
          6. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 1 at&#xD;
             Screening.&#xD;
&#xD;
          7. Is aged 18 years or older.&#xD;
&#xD;
          8. Has life expectancy of at least 6 months in the best judgement of the investigator.&#xD;
&#xD;
          9. Is willing and able to sign a written informed consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients who, in the investigator's opinion, have progressed rapidly on their previous&#xD;
             anticancer treatment (e.g., did not achieve any response [CR, PR, or SD]).&#xD;
&#xD;
          2. Has brain metastases (unless they have received prior treatment and are controlled and&#xD;
             stable for at least 6 weeks before study enrolment) or leptomeningeal spread of&#xD;
             disease.&#xD;
&#xD;
          3. Has positive serological test for hepatitis C virus (HCV), hepatitis B virus (HBV),&#xD;
             surface antigen (HBsAg), positive HBV core antibody. Human immunodeficiency virus&#xD;
             (HIV).&#xD;
&#xD;
          4. Has other concomitant or prior malignant disease,&#xD;
&#xD;
          5. Has an active, known or suspected autoimmune disease.&#xD;
&#xD;
          6. Is receiving systemic immunosuppression including systemic steroids or the use of&#xD;
             immunosuppressive agents for any concurrent condition.&#xD;
&#xD;
          7. Has known allergy to aminoglycosides or kanamycin or any study treatment component.&#xD;
&#xD;
          8. Has history of toxic shock syndrome.&#xD;
&#xD;
          9. Has history of idiopathic pulmonary fibrosis, drug-induced pneumonitis, organising&#xD;
             pneumonia, immune enteritis or active pneumonitis.&#xD;
&#xD;
         10. Has evidence or history of clinically significant cardiac disease including congestive&#xD;
             heart failure&#xD;
&#xD;
         11. Has ongoing toxicity from prior therapy&#xD;
&#xD;
         12. Has severe infections within 4 weeks prior to study start&#xD;
&#xD;
         13. Current participation in a clinical trial&#xD;
&#xD;
         14. Has received investigational drug within 30 days before study entry.&#xD;
&#xD;
         15. Has received vaccination against infections within 30 days before study entry.&#xD;
&#xD;
         16. Has had prior treatment with CD137, anti-PD-1, or anti-PD-L1 therapeutic antibody or&#xD;
             other immune checkpoint targeting agents.&#xD;
&#xD;
         17. Has known hypersensitivity to any component of the atezolizumab or VB10.16&#xD;
             formulation.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Cliniques Universitaires Saint-Luc</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hopital de Libramont</name>
      <address>
        <city>Bruxelles</city>
        <zip>1200</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitair Ziekenhuis Gent (Uz Gent)</name>
      <address>
        <city>Gent</city>
        <zip>9000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chu Ucl Namur</name>
      <address>
        <city>Namur</city>
        <zip>5000</zip>
        <country>Belgium</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment for Women's Health - Nadezhda Sofia</name>
      <address>
        <city>Sofia</city>
        <zip>1330</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Multiprofile Hospital for Active Treatment &quot;Sv. Ivan Rilski&quot;</name>
      <address>
        <city>Sofia</city>
        <zip>1431</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Multiprofile Hospital for Active Treatment &quot;Serdika&quot;&quot; EOOD</name>
      <address>
        <city>Sofia</city>
        <zip>1527</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Multiprofile Hospital For Active Treatment Sofiamed</name>
      <address>
        <city>Sofia</city>
        <zip>1797</zip>
        <country>Bulgaria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Masaryk Memorial Cancer Institute</name>
      <address>
        <city>Brno</city>
        <zip>65653</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemocnice Pardubickeho Kraje Pardubicka Nemocnice</name>
      <address>
        <city>Pardubice</city>
        <zip>53203</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Hospital Kralovske Vinohrady</name>
      <address>
        <city>Praha</city>
        <zip>10034</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nemocnice Na Bulovce</name>
      <address>
        <city>Praha</city>
        <zip>180 81</zip>
        <country>Czechia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Augsburg</name>
      <address>
        <city>Augsburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University Clinic Carl Gustav Carus</name>
      <address>
        <city>Dresden</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitatsklinikum Hamburg-Eppendorf</name>
      <address>
        <city>Hamburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Fakulat Mannheim Der Universitat Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oslo University Hospital</name>
      <address>
        <city>Oslo</city>
        <zip>0379</zip>
        <country>Norway</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jagielońskie Centum Innowacji, Centrum Badań Klinicznych JCI</name>
      <address>
        <city>Kraków</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wielkopolskie Centrum Onkologii</name>
      <address>
        <city>Poznań</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>'Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie</name>
      <address>
        <city>Warsaw</city>
        <country>Poland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Belgium</country>
    <country>Bulgaria</country>
    <country>Czechia</country>
    <country>Germany</country>
    <country>Norway</country>
    <country>Poland</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>April 28, 2020</study_first_submitted>
  <study_first_submitted_qc>May 26, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</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 7, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Metastatic</keyword>
  <keyword>Recurrent</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Uterine Cervical Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Atezolizumab</mesh_term>
  </intervention_browse>
  <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/NCT04405349
org study id: VB C-02
nct id: NCT04405349
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This phase IIa study is designed to evaluate the safety and efficacy of multiple dosing with
      VB10.16 immunotherapy in combination with atezolizumab in patients with advanced or recurrent
      non-resectable HPV16-positive cervical cancer, who failed or are not eligible for current
      standard of care.
Patients will receive up to 11 intramuscular (i.m.) vaccinations of VB10.16, for up to 48
      weeks from first vaccination. Patients will receive 5 vaccinations of 3 mg VB10.16 during the
      first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks from first
      immunisation (total of 11 vaccinations). Patients will receive up to 17 infusions of
      atezolizumab for up to 48 weeks from first treatment. Atezolizumab (1200 mg) will be
      administered as an intravenous (i.v.) infusion every 3 weeks. A follow-up period of up to 12
      months will follow the 48 week treatment period.

      Response to the VB10.16 and atezolizumab combination will be assessed by computed tomography
      (CT)/magnetic resonance imaging (MRI) at every 9 weeks throughout the treatment period
      according to the RECIST 1.1 criteria.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and severity of adverse events (AEs)
time frame: 48 weeks (1 year follow-up)
description: The number and percentage of participants that experience an adverse event (AE
measure: Overall response rate (ORR) using Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 at any time during the study
time frame: 48 weeks (1 year follow-up)
description: ORR as assessed by RECIST v1.1
measure: Duration of response (DOR)
time frame: 48 weeks (1 year follow-up)
description: Estimate the duration of response (DOR) in patients with advanced cervical cancer
measure: Progression-free survival (PFS)
time frame: 48 weeks (1 year follow-up)
description: Estimate the Progression-free survival (PFS) in patients with advanced cervical cancer
measure: Overall survival (OS)
time frame: 48 weeks (1 year follow-up)
description: Overall survival (OS) in patients with advanced cervical cancer
measure: Evaluate immunogenicity of VB10.16 in combination with atezolizumab by analysing HPV16 E6/E7-specific cellular immune responses
time frame: 48 weeks (1 year follow-up)
description: Systemic T-cell response
measure: Assess predictive biomarkers, such as programmed death-ligand 1 (PD-L1) in tumour material and investigate changes in tumour microenvironment by immunohistochemistry (IHC) and/or gene expression
time frame: 48 weeks (1 year follow-up)
description: T cell infiltration, PD-L1 expression or other immune-oncology related genes
measure: Correlating HPV16 circulating tumour DNA (ctDNA) in plasma with clinical response using RECIST 1.1
time frame: 48 weeks (1 year follow-up)
description: ctDNA
arm group label: Combination Therapy
arm group type: Experimental
description: VB10.16 vaccinations. 11 intramuscular (i.m.) vaccinations for up to 48 weeks from first vaccination. 5 vaccinations of 3 mg VB10.16 during the first 12 weeks, followed by vaccination every 6 weeks for up to 48 weeks + Atezolizumab (1200 mg) intravenous (i.v.) infusion every 3 weeks.
intervention type: Biological
intervention name: VB10.16
description: Vaccination
arm group label: Combination Therapy
intervention type: Biological
intervention name: Atezolizumab
description: Intravenously infusion
arm group label: Combination Therapy
other name: Tecentriq
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
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country: Belgium
country: Bulgaria
country: Czechia
country: Germany
country: Norway
country: Poland
responsible party type: Sponsor
mesh term: Uterine Cervical Neoplasms
mesh term: Atezolizumab
sharing ipd: No