<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/NCT02992977</url>
  </required_header>
  <id_info>
    <org_study_id>C-600-01</org_study_id>
    <nct_id>NCT02992977</nct_id>
  </id_info>
  <brief_title>Safety and Tolerability Study of AutoSynVax™ Vaccine in Subjects With Advanced Cancer</brief_title>
  <official_title>A Phase 1 Study of Safety and Tolerability of AutoSynVax™ Vaccine as a Single Agent in Subjects With Advanced Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Agenus Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Agenus Inc.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Open-label Phase 1 study of AutoSynVax™ vaccine with QS-21 Stimulon® adjuvant in subjects&#xD;
      with advanced cancer&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label Phase 1 study to determine the safety and tolerability of single-agent&#xD;
      treatment with AutoSynVax™ vaccine with QS-21 Stimulon® adjuvant in subjects with advanced&#xD;
      cancer that is refractory to standard therapies and a life expectancy of ≥6 months from the&#xD;
      time tissue is obtained. A minimum of 6 (≤20) subjects will be enrolled to receive every&#xD;
      other week subcutaneous injection of 240 μg AutoSynVax™ vaccine + 50 μg QS-21 Stimulon®&#xD;
      adjuvant for up to 1 year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    To enable development of an enhanced version of the vaccine.&#xD;
  </why_stopped>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <phase>Phase 1</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 of Treatment-Emergence Adverse Events (Safety and Tolerability)</measure>
    <time_frame>From first administration to 30 days from last dose.</time_frame>
    <description>AEs, irAEs, according to NCI CTCAE version 4.03.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Recommended dose for further development</measure>
    <time_frame>28 days from first dose</time_frame>
    <description>After 2 doses (administered every 2 weeks), if there are &lt;2 treatment-limiting toxicities (TLTs) in the first 6 subjects, AutoSynVax™ vaccine will be considered safe for further development.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>From first administration until death, or up to study duration (18 - 24 months)</time_frame>
    <description>Duration of survival</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free survival (PFS)</measure>
    <time_frame>6 Months after last dose is administered.</time_frame>
    <description>From time of first administration per RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate (ORR)</measure>
    <time_frame>6 Months after last dose is administered.</time_frame>
    <description>From time of first administration per RECIST v1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>T-cell response</measure>
    <time_frame>6 Months after last administration.</time_frame>
    <description>T-cell response to tumor specific neo-epitopes in the vaccine</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Advanced Cancer</condition>
  <arm_group>
    <arm_group_label>AutoSynVax™ vaccine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AutoSynVax™ vaccine + QS-21 Stimulon® adjuvant</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AutoSynVax™ vaccine</intervention_name>
    <description>AutoSynVax™ vaccine + QS-21 Stimulon® adjuvant</description>
    <arm_group_label>AutoSynVax™ vaccine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Prior to vaccine production -&#xD;
&#xD;
          1. Diagnosis of advanced cancer (solid tumor) that:&#xD;
&#xD;
               1. May be receiving or about to start another line of therapy.&#xD;
&#xD;
               2. If on a line of therapy or about to start a new line of therapy, it is&#xD;
                  anticipated that the treatment may provide short-term tumor control.&#xD;
&#xD;
          2. Available tissue from an archival tissue sample or tissue from a biopsy done during&#xD;
             the initial screen, or both. If archival tissue is not available or tissue is not&#xD;
             mainly tumor, subjects must be willing to undergo a biopsy or surgery to remove some&#xD;
             or all of their tumor for next generation sequencing. New tissue should be obtained&#xD;
             prior to starting a new line of therapy, if applicable.&#xD;
&#xD;
          3. Minimum estimated life expectancy of 6 months.&#xD;
&#xD;
          4. Age 18 years or older.&#xD;
&#xD;
          5. Signed written informed consent to allow transfer of tumor tissue and production of&#xD;
             vaccine.&#xD;
&#xD;
          6. Discussion about each patient should occur with the Medical Monitor to confirm&#xD;
             eligibility.&#xD;
&#xD;
        Prior to Treatment -&#xD;
&#xD;
        Patients who had vaccine manufactured but were treated with an additional line of treatment&#xD;
        may start vaccine if they continue to meet the remaining eligibility criteria.:&#xD;
&#xD;
          1. Diagnosis of advanced cancer (solid tumor) that is refractory to standard therapies.&#xD;
&#xD;
          2. Signed written informed consent for treatment.&#xD;
&#xD;
          3. Minimum estimated life expectancy of 3 months.&#xD;
&#xD;
          4. Eastern Cooperative Oncology Group (ECOG) performance status &lt;2.&#xD;
&#xD;
          5. Adequate bone marrow function (absolute neutrophil count [ANC] ≥1,500/mm^3; absolute&#xD;
             lymphocyte count [ALC] ≥500/mm^3; platelet count 100,000/mm^3), adequate liver&#xD;
             function (serum glutamic oxaloacetic transaminase [SGOT]/aspartate aminotransferase&#xD;
             [AST] and alkaline phosphatase &lt;2.5 times the institutional upper limit of normal&#xD;
             [IULN], total bilirubin &lt;1.5 mg/dL), and adequate renal function (creatinine &lt;1.5 x&#xD;
             IULN).&#xD;
&#xD;
          6. Adequate cardiac function (New York Heart Association [NYHA] class ≤II).&#xD;
&#xD;
          7. All participants (males and females) must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control, abstinence) prior to study treatment and&#xD;
             for the duration of study participation.&#xD;
&#xD;
        Female subjects of childbearing potential should have a negative serum pregnancy test at&#xD;
        pre-treatment visit and within 72 hours prior to receiving the first dose of study&#xD;
        medication.&#xD;
&#xD;
        Female subjects of childbearing potential must agree to use 2 methods of birth control or&#xD;
        be surgically sterile, or abstain from heterosexual activity prior to receiving the first&#xD;
        dose of study medication through 30 days after the last dose of study medication.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects must not meet any of the following exclusion criteria at the time of tumor&#xD;
        procurement. All exclusion criteria must be confirmed prior to treatment.&#xD;
&#xD;
          1. Diagnosis of immunodeficiency or actively receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to the first dose of trial&#xD;
             treatment.&#xD;
&#xD;
          2. Corticosteroid dependency.&#xD;
&#xD;
          3. Requirement for immunosuppressive medication aside from corticosteroids.&#xD;
&#xD;
          4. Active or history of any autoimmune disease (subjects with diabetes type 1, vitiligo,&#xD;
             psoriasis, hypo-, or hyperthyroid disease not requiring immunosuppressive treatment&#xD;
             are eligible) or immunodeficiencies.&#xD;
&#xD;
          5. History of treated or untreated brain metastases or leptomeningeal spread of disease.&#xD;
&#xD;
          6. History or current evidence of any condition, therapy, or laboratory abnormality that&#xD;
             might confound the results of the trial, interfere with the subject's participation&#xD;
             for the full duration of the trial, or is not in the best interest of the subject to&#xD;
             participate, in the opinion of the treating investigator.&#xD;
&#xD;
          7. Known medical, psychiatric or substance abuse disorders that would preclude&#xD;
             participation in the study.&#xD;
&#xD;
          8. Uncontrolled intercurrent illness, including, but not limited to, ongoing or active&#xD;
             infection, interstitial lung disease or active, non-infectious pneumonitis,&#xD;
             symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements.&#xD;
&#xD;
          9. Known to be positive for human immunodeficiency virus (HIV). Testing is not required&#xD;
             in the absence of history or high index of suspicion.&#xD;
&#xD;
         10. Intolerance of prior immunotherapy treatment necessitating cessation of therapy.&#xD;
&#xD;
         11. History of intolerance or allergic reactions attributed to compounds of similar&#xD;
             chemical or biologic composition to AutoSynVax™ vaccine or QS-21.&#xD;
&#xD;
         12. Women who are pregnant or breastfeeding.&#xD;
&#xD;
         13. Inability to comply with protocol.&#xD;
&#xD;
        Prior to Treatment - Subjects must not meet any of the following exclusion criteria prior&#xD;
        to treatment in addition to the other exclusion criteria listed above.&#xD;
&#xD;
          1. Receipt of anticancer medications or investigational drugs within the following&#xD;
             intervals before first administration of study drug:&#xD;
&#xD;
               1. ≤14 days for chemotherapy, targeted small molecule therapy, anticancer hormone&#xD;
                  therapy or radiation therapy. Subjects must also not have had radiation&#xD;
                  pneumonitis as a result of treatment, and cannot participate in the study if they&#xD;
                  are on chronic corticosteroids for radiation pneumonitis or other reasons. A&#xD;
                  1-week washout is permitted for palliative radiation to non-CNS disease with&#xD;
                  sponsor approval.&#xD;
&#xD;
               2. Note: Bisphosphonates and denosumab are permitted medications. Novel imaging&#xD;
                  agents that have Phase 1 safety data and have not demonstrated therapeutic&#xD;
                  activity are also permitted.&#xD;
&#xD;
               3. ≤28 days for a prior immunotherapy.&#xD;
&#xD;
               4. ≤28 days for prior monoclonal antibody used for anticancer therapy with the&#xD;
                  exception of denosumab.&#xD;
&#xD;
               5. ≤7 days for immunosuppressive-based treatment for any reason. Systemic&#xD;
                  corticosteroids are not allowed.&#xD;
&#xD;
                  Note: Use of inhaled or topical corticosteroid use for radiographic procedures is&#xD;
                  permitted.&#xD;
&#xD;
                  Note: Patients receiving physiologic steroid replacement for adrenal&#xD;
                  insufficiency are eligible (i.e. &lt; 10 mg prednisone per day).&#xD;
&#xD;
                  Note: The use of physiologic corticosteroid replacement therapy may be approved&#xD;
                  after consultation with the sponsor.&#xD;
&#xD;
               6. ≤28 days before the first dose for all other investigational study drugs or&#xD;
                  devices.&#xD;
&#xD;
          2. Receipt of other investigational agents or other anticancer therapies during treatment&#xD;
             with AutoSynVax™ vaccine.&#xD;
&#xD;
          3. Receipt of a live vaccine within 30 days prior to the first dose of trial treatment.&#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>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Agenus Inc.</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>School of Medicine at the University of Miami</name>
      <address>
        <city>Miami</city>
        <state>Florida</state>
        <zip>33136</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Comprehensive Cancer Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2020</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>December 12, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 14, 2016</study_first_posted>
  <last_update_submitted>May 29, 2020</last_update_submitted>
  <last_update_submitted_qc>May 29, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Vaccine, neoantigen</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</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/NCT02992977
org study id: C-600-01
nct id: NCT02992977
lead sponsor: 
has dmc: No
Open-label Phase 1 study of AutoSynVax™ vaccine with QS-21 Stimulon® adjuvant in subjects
      with advanced cancer
This is an open-label Phase 1 study to determine the safety and tolerability of single-agent
      treatment with AutoSynVax™ vaccine with QS-21 Stimulon® adjuvant in subjects with advanced
      cancer that is refractory to standard therapies and a life expectancy of ≥6 months from the
      time tissue is obtained. A minimum of 6 (≤20) subjects will be enrolled to receive every
      other week subcutaneous injection of 240 μg AutoSynVax™ vaccine + 50 μg QS-21 Stimulon®
      adjuvant for up to 1 year.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergence Adverse Events (Safety and Tolerability)
time frame: From first administration to 30 days from last dose.
description: AEs, irAEs, according to NCI CTCAE version 4.03.
measure: Recommended dose for further development
time frame: 28 days from first dose
description: After 2 doses (administered every 2 weeks), if there are <2 treatment-limiting toxicities (TLTs) in the first 6 subjects, AutoSynVax™ vaccine will be considered safe for further development.
measure: Overall survival (OS)
time frame: From first administration until death, or up to study duration (18 - 24 months)
description: Duration of survival
measure: Progression-free survival (PFS)
time frame: 6 Months after last dose is administered.
description: From time of first administration per RECIST v1.1
measure: Objective response rate (ORR)
time frame: 6 Months after last dose is administered.
description: From time of first administration per RECIST v1.1
measure: T-cell response
time frame: 6 Months after last administration.
description: T-cell response to tumor specific neo-epitopes in the vaccine
arm group label: AutoSynVax™ vaccine
arm group type: Experimental
description: AutoSynVax™ vaccine + QS-21 Stimulon® adjuvant
intervention type: Biological
intervention name: AutoSynVax™ vaccine
description: AutoSynVax™ vaccine + QS-21 Stimulon® adjuvant
arm group label: AutoSynVax™ vaccine
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Agenus Inc.
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No