<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/NCT03291002</url>
  </required_header>
  <id_info>
    <org_study_id>CV-8102-008</org_study_id>
    <nct_id>NCT03291002</nct_id>
  </id_info>
  <brief_title>Study of Intratumoral CV8102 in cMEL, cSCC, hnSCC, and ACC</brief_title>
  <official_title>Phase I Study of Intratumoral CV8102 in Patients With Advanced Melanoma, Squamous Cell Carcinoma of the Skin, Squamous Cell Carcinoma of the Head and Neck, or Adenoid Cystic Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>CureVac</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Syneos Health</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Cromos Pharma LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>CureVac</source>
  <oversight_info>
    <has_dmc>Yes</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 study evaluates intratumoral administration of CV8102 in patients with advanced&#xD;
      melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck,&#xD;
      or adenoid cystic carcinoma.&#xD;
&#xD;
      Patients will receive CV8102 as single agent or in combination with SoC anti-PD-1 therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">September 25, 2017</start_date>
  <completion_date type="Anticipated">February 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>Open-label, cohort-based, dose escalation and expansion study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose determination for dose escalation cohorts</measure>
    <time_frame>2 weeks</time_frame>
    <description>Maximum tolerated dose (MTD) and recommended dose (RD), respectively, for CV8102 alone&#xD;
MTD and recommended combination dose (RCD) for CV8102 in combination with the standard dose of an anti-PD-1 antagonist</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of treatment related (Serious) Adverse Events (Tolerability and Safety profile)</measure>
    <time_frame>up to 12 months (end of study)</time_frame>
    <description>• Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 antagonists</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>up to 12 months (end of study)</time_frame>
    <description>• Anti-tumor activity of CV8102 per irRECIST and RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease status</measure>
    <time_frame>6 months</time_frame>
    <description>• Tumor Assessment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tumor response</measure>
    <time_frame>up to 12 months (end of study)</time_frame>
    <description>• Extent of tumor response at injected and non-injected lesions, if applicable</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>up to 12 months (end of study)</time_frame>
    <description>• Survival time</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">98</enrollment>
  <condition>Melanoma (Skin)</condition>
  <condition>Squamous Cell Carcinoma of the Skin</condition>
  <condition>Carcinoma, Squamous Cell of Head and Neck</condition>
  <condition>Carcinoma, Adenoid Cystic</condition>
  <arm_group>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation of CV8102</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optional expansion cohorts of CV8102</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Dose escalation of CV8102 + anti-PD-1 therapy</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Optional expansion of CV8102 + anti-PD-1 therapy</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CV8102</intervention_name>
    <description>CV8102 alone</description>
    <arm_group_label>Cohort A</arm_group_label>
    <arm_group_label>Cohort B</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>CV8102 + anti-PD-1 therapy</intervention_name>
    <description>CV8102 in combination with standard of care anti-PD-1 therapy</description>
    <arm_group_label>Cohort C</arm_group_label>
    <arm_group_label>Cohort D</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria:&#xD;
&#xD;
          1. Patients enrolled into Cohorts A and B (single agent CV8102) must have:&#xD;
&#xD;
               -  histologically confirmed advanced cutaneous melanoma, cutaneous squamous cell&#xD;
                  carcinoma, head and neck squamous cell carcinoma, or adenoid cystic carcinoma&#xD;
                  with documented disease progression&#xD;
&#xD;
               -  not amenable to surgical resection or locoregional radiation therapy with&#xD;
                  curative intent&#xD;
&#xD;
               -  at least 1 line of anti-cancer therapy for advanced disease (except adenoid&#xD;
                  cystic carcinoma) and documented Progression&#xD;
&#xD;
               -  cutaneous melanoma Cohort B3: Willing to undergo baseline and post-baseline&#xD;
                  biopsy of the lesion which is to be injected&#xD;
&#xD;
          2. Patients enrolled into Cohort C (CV8102 in combination with anti-PD-1 therapy) must&#xD;
             have&#xD;
&#xD;
               -  histologically confirmed advanced cMEL or hnSCC&#xD;
&#xD;
               -  indication for anti-PD-1 therapy or currently receiving anti-PD-1 therapy with&#xD;
                  stable of slowly progressing disease after at last 8 weeks (hnSCC) or 12 weeks&#xD;
                  (cMEL) of anti-PD-1 therapy prior to Day 1&#xD;
&#xD;
          3. Patients enrolled into Cohort D1 (CV8102 in combination with anti-PD-1 therapy) must&#xD;
             have&#xD;
&#xD;
               -  histologically confirmed advanced cMEL&#xD;
&#xD;
               -  either anti-PD-1 naive patients with indication for anti-PD-1 therapy (Cohort&#xD;
                  D1a) or patients refractory to anti-PD-1 therapy (Cohort D1b)&#xD;
&#xD;
               -  Presence of measurable lesion(s) according to RECIST 1.1, not intended for&#xD;
                  injection&#xD;
&#xD;
               -  Willing to undergo tumor biopsies at specific timepoints (Cohort D1a: baseline;&#xD;
                  Cohort D1b baseline and post-baseline biopsy of the injected lesion - only for&#xD;
                  selected sites)&#xD;
&#xD;
          4. Patients enrolled into Cohort D2 (CV8102 in combination with anti-PD-1 therapy) must&#xD;
             have&#xD;
&#xD;
               -  histologically confirmed advanced hnSCC&#xD;
&#xD;
               -  indication for treatment with first-line pembrolizumab (patients naive to&#xD;
                  anti-PD-1/anti-PD-L1)&#xD;
&#xD;
               -  PD-L1 combined positive score ≥ 1% according to local practice&#xD;
&#xD;
          5. Presence of at least one injectable tumor lesion that is measurable according to&#xD;
             RECIST 1.1&#xD;
&#xD;
          6. Recovered from prior toxicities to CTCAE grade ≤ 1 or grade ≤ 2&#xD;
&#xD;
          7. Resolution of CPI-related adverse effects, if applicable (including irAEs) back to&#xD;
             CTCAE grade 0/1&#xD;
&#xD;
          8. ECOG PS 0 or 1&#xD;
&#xD;
          9. 18 years of age or older&#xD;
&#xD;
         10. Adequate hematologic, renal, hepatic and coagulation function&#xD;
&#xD;
         11. Use of effective contraception&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          1. Rapidly progressing multi-focal metastatic or acutely life threatening disease&#xD;
&#xD;
          2. Prior use of topical/localTLR-7/8 agonists within the past 6 months&#xD;
&#xD;
          3. Clinically active central nervous system metastases and/or carcinomatous meningitis&#xD;
             (patients with stable brain metastases are eligible)&#xD;
&#xD;
          4. Ocular and mucosal melanoma&#xD;
&#xD;
          5. Prior anti-cancer therapy within specified time-periods depending on the indication&#xD;
&#xD;
          6. Tumor lesions that are to be injected close to major blood vessels or nerves, or whose&#xD;
             injection could potentially result in clinical adverse effects if post-treatment tumor&#xD;
             swelling or inflammation were to occur&#xD;
&#xD;
          7. Lesions that are to be injected in previously irradiated areas unless progressive&#xD;
             tumor growth has been demonstrated (no prior irradiation of injected lesions on&#xD;
             patients with melanoma)&#xD;
&#xD;
          8. History of active coagulation or bleeding disorder or need for ongoing therapeutic&#xD;
             anticoagulation that cannot be safely interrupted at th etime of IT injection or&#xD;
             biopsy du eto Underlying medical conditions; patients with melanoma and cutaneous&#xD;
             squamous cell carcinoma with controlled oral anticoagulation are eligible&#xD;
&#xD;
          9. Treatment with any investigational anticancer agent within 30 days or 5 half-lives&#xD;
             (whichever is longer) prior to the first dose of study drug or planned during the&#xD;
             study&#xD;
&#xD;
         10. Acute hypophysitis or endocrinopathies that are not adequately controlled by hormonal&#xD;
             replacement therapy or thyreostatic treatment&#xD;
&#xD;
         11. Use of immune modulating drugs or immunologically active topical therapies within 28&#xD;
             days of administration of the first dose of study drug&#xD;
&#xD;
         12. Chronic systemic immunosuppressive therapy including chronic corticosteroids within 28&#xD;
             days of the first dose of study drug (except physiological maintenance/replacement&#xD;
             steroid doses, topical steroids outside the injected lesion or inhaled steroids);&#xD;
             patients are eligible if steroid requirement is &lt; 10 mg/day of prednisone (or&#xD;
             equivalent) for at least 2 weeks&#xD;
&#xD;
         13. History of active autoimmune disease requiring immunosuppressive medication (except&#xD;
             Vitiligo and except CPI-mediated irAEs)&#xD;
&#xD;
         14. Known hematologic malignancy or malignant primary solid tumor that have occured or&#xD;
             reoccurred within the previous 5 years&#xD;
&#xD;
         15. Recent thromboembolic complications, or clinically significant cardiovascular disease,&#xD;
             or any other uncontrolled illness that would pose a risk to patient safety&#xD;
&#xD;
         16. Severe infection or acute inflammatory state&#xD;
&#xD;
         17. Seropositivity for human immunodeficiency virus (HIV), hepatitis B virus (HBV) surface&#xD;
             antigen (except in previously vaccinated patients) or hepatitis C virus (HCV)&#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>Thomas Eigentler, Prof. Dr.</last_name>
    <role>Principal Investigator</role>
    <affiliation>thomas.eigentler@charite.de</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of Graz</name>
      <address>
        <city>Graz</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinik für Dermatologie der Paracelsus medizinischen Privatuniversität Salzburg</name>
      <address>
        <city>Salzburg</city>
        <country>Austria</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital Saint Louis</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Institut Gustave Roussy</name>
      <address>
        <city>Paris</city>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Charité Benjamin Franklin</name>
      <address>
        <city>Berlin</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Klinik III, Universitätsklinikum Bonn, Hämatologie, Immunonkologie und Rheumatologie</name>
      <address>
        <city>Bonn</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Elbe-Klinikum-Buxtehude, Hautkrebszentrum</name>
      <address>
        <city>Buxtehude</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Erlangen,Hautklinik, Internistisches Zentrum (INZ)</name>
      <address>
        <city>Erlangen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Nationales Centrum für Tumorerkrankungen (NCT) Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Schleswig-Holstein, Klinik für Dermatologie, Allergologie und Venerologie</name>
      <address>
        <city>Lübeck</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fachklinik Hornheide</name>
      <address>
        <city>Münster</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Münster, Klinik für Hautkrankheiten, ZiD- Zentrum für innovative Dermatologie</name>
      <address>
        <city>Münster</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitäts-Hautklinik, Abtl. Dermatologische Onkologie</name>
      <address>
        <city>Tübingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Center for Personalized Oncology, I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBI &quot;National Medical Research Center of Oncology n.a. N.N. Blokhin&quot; of the Ministry of Healthcare of the Russian Federation</name>
      <address>
        <city>Moscow</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>FSBI &quot;National Medical Research Oncology Center n.a. N.N. Petrov</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saint-Petersburg State University, Clinic of advanced medical technologies n. a. Nicolay I. Pirogov.</name>
      <address>
        <city>Saint Petersburg</city>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Duran i Reynals - Institut Catala dOncologia ICO</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitari Vall d'Hebron</name>
      <address>
        <city>Barcelona</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Ramon y Cajal</name>
      <address>
        <city>Madrid</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Virgen de la Victoria</name>
      <address>
        <city>Málaga</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hospital Universitario Marqus de Valdecilla Santander</name>
      <address>
        <city>Santander</city>
        <country>Spain</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Austria</country>
    <country>France</country>
    <country>Germany</country>
    <country>Russian Federation</country>
    <country>Spain</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>September 15, 2017</study_first_submitted>
  <study_first_submitted_qc>September 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>November 3, 2021</last_update_submitted>
  <last_update_submitted_qc>November 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 4, 2021</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>Melanoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Skin Neoplasms</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
    <mesh_term>Carcinoma, Adenoid Cystic</mesh_term>
  </condition_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/NCT03291002
org study id: CV-8102-008
nct id: NCT03291002
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates intratumoral administration of CV8102 in patients with advanced
      melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck,
      or adenoid cystic carcinoma.

      Patients will receive CV8102 as single agent or in combination with SoC anti-PD-1 therapy.
allocation: Non-Randomized
intervention model: Single Group Assignment
intervention model description: Open-label, cohort-based, dose escalation and expansion study
primary purpose: Treatment
masking: None (Open Label)
measure: Dose determination for dose escalation cohorts
time frame: 2 weeks
description: Maximum tolerated dose (MTD) and recommended dose (RD), respectively, for CV8102 alone
MTD and recommended combination dose (RCD) for CV8102 in combination with the standard dose of an anti-PD-1 antagonist
measure: Incidence of treatment related (Serious) Adverse Events (Tolerability and Safety profile)
time frame: up to 12 months (end of study)
description: • Tolerability and safety profile of CV8102 alone and in combination with anti-PD-1 antagonists
measure: Tumor response
time frame: up to 12 months (end of study)
description: • Anti-tumor activity of CV8102 per irRECIST and RECIST 1.1
measure: Disease status
time frame: 6 months
description: • Tumor Assessment
measure: Tumor response
time frame: up to 12 months (end of study)
description: • Extent of tumor response at injected and non-injected lesions, if applicable
measure: Survival
time frame: up to 12 months (end of study)
description: • Survival time
arm group label: Cohort A
arm group type: Experimental
description: Dose escalation of CV8102
arm group label: Cohort B
arm group type: Experimental
description: Optional expansion cohorts of CV8102
arm group label: Cohort C
arm group type: Experimental
description: Dose escalation of CV8102 + anti-PD-1 therapy
arm group label: Cohort D
arm group type: Experimental
description: Optional expansion of CV8102 + anti-PD-1 therapy
intervention type: Biological
intervention name: CV8102
description: CV8102 alone
arm group label: Cohort A
arm group label: Cohort B
intervention type: Biological
intervention name: CV8102 + anti-PD-1 therapy
description: CV8102 in combination with standard of care anti-PD-1 therapy
arm group label: Cohort C
arm group label: Cohort D
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Thomas Eigentler, Prof. Dr.
role: Principal Investigator
affiliation: thomas.eigentler@charite.de
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
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facility: 
facility: 
country: Austria
country: France
country: Germany
country: Russian Federation
country: Spain
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Melanoma
mesh term: Carcinoma, Squamous Cell
mesh term: Skin Neoplasms
mesh term: Squamous Cell Carcinoma of Head and Neck
mesh term: Carcinoma, Adenoid Cystic
sharing ipd: No