<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/NCT03803397</url>
  </required_header>
  <id_info>
    <org_study_id>PV001-001 (Arm 1)</org_study_id>
    <nct_id>NCT03803397</nct_id>
  </id_info>
  <brief_title>Arm 1: Lysate Pulsed Dendritic Cells (PV-001-DC) in Patients With Melanoma</brief_title>
  <official_title>A Study to Evaluate the Safety and Efficacy of Intratumoral Injection of PV-001-DV in Combination With Infusion of PV-001-DC in Patients With Advanced Melanoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>PrimeVax Immuno-Oncology Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>PrimeVax Immuno-Oncology Inc.</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Autologous monocyte-derived dendritic cells pulsed with tumor lysate (PV-001-DC) will be&#xD;
      given to a group of 3 people. If this is found to be safe, it will be given to up to 7 other&#xD;
      people, for a total of up to 10 people in this arm. This will be the first study of&#xD;
      PV-001-DC.&#xD;
&#xD;
      Eligible patients must be progressing after having completed prior therapy with a PD-1/PD-L1&#xD;
      antagonist alone or in combination with anti-CTLA-4. If the patient is positive for BRAF, the&#xD;
      patient must have progressed on at least one BRAF inhibitor in addition to a PD-1/PD-L1&#xD;
      inhibitor alone or in combination with CTLA-4 for metastatic melanoma.&#xD;
&#xD;
      Although other kinds of dendritic cells (DCs) have been approved to treat some forms of&#xD;
      cancer, they have not been approved to treat melanoma. PV-001-DC is a special kind of DCs&#xD;
      that is combined with tumor lysate. The study procedures will start with the removal of a&#xD;
      small amount of tumor tissue processed into protein fragments (lysate). There will also be&#xD;
      collection of white blood cells through apheresis (a procedure in which blood is drawn from a&#xD;
      patient and separated into its different cell types), the white blood cells will be collected&#xD;
      and the remainder returned to the patient. Dendritic cells will be grown from the collected&#xD;
      white blood cells and combined with the lysate to form PV-001-DC.&#xD;
&#xD;
      On the first day of study treatment, patients will go to the clinic and have a needle placed&#xD;
      in a vein. The PV-001-DC product will be infused into the patient's vein. Approximately every&#xD;
      3 weeks, for a total of 4 treatments, patients will receive additional infusions of&#xD;
      PV-001-DC. Patients will be at the clinic for at least 1 hour following the end of the&#xD;
      PV-001-DC infusion and if they feel fine, they may go home.&#xD;
&#xD;
      Scans will be performed during the study at different times to see if their tumors have&#xD;
      changed in size. Patients will also have their blood and small samples of tumors tested for&#xD;
      changes to the immune system. After 365 days, the trial will be completed for that patient.&#xD;
&#xD;
      Investigators will monitor patients carefully for any harmful side effects. The side effects&#xD;
      in people cannot be completely known ahead of time&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">April 1, 2024</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">August 30, 2024</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 and severity of Treatment-Emergent Adverse Events</measure>
    <time_frame>365 days</time_frame>
    <description>Treatment-Emergent Adverse Event Incidence in patients receiving IV infusion of PV-001-DC</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Overall Response Rate (ORR)</measure>
    <time_frame>365 days</time_frame>
    <description>Tumor response will be measured per investigator's assessment according to RECIST v1.1 and iRECIST</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-Free Survival (PFS)</measure>
    <time_frame>365 days</time_frame>
    <description>The length of time during the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse, up to the end of the study</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>365 days</time_frame>
    <description>Overall Survival is measured from the date of enrollment to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date, up to the end of the study</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Metastatic Melanoma</condition>
  <arm_group>
    <arm_group_label>PV-001-DC alone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Autologous Monocyte-derived Lysate Pulsed Dendritic Cells</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>PV-001-DC</intervention_name>
    <description>Patient-specific cellular therapeutic for cancer immunotherapy</description>
    <arm_group_label>PV-001-DC alone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Biopsy confirmed patients with un-resectable AJCC Stage III or IV melanoma who have&#xD;
             measurable disease. Measurable disease is required, and is defined as tumor can be&#xD;
             measured in two dimensions.&#xD;
&#xD;
          -  Patient must have progressed with prior therapy with a PD-1 / PD-L1 antagonist alone&#xD;
             or in combination with anti-CTLA-4. If the patient is positive for BRAF, the patient&#xD;
             must have progressed on at least one BRAF inhibitor in addition to a PD-1 / PD-L1&#xD;
             inhibitor alone or in combination with CTLA4 for metastatic melanoma.&#xD;
&#xD;
          -  Tumor specimens must be available for tumor lysates and immunological studies.&#xD;
&#xD;
          -  ECOG Performance Status of ≤ 2 (corresponds to a Karnofsky Performance Status (KPS) of&#xD;
             ≥ 70).&#xD;
&#xD;
          -  Patients must be 18 years or older and able to give informed consent.&#xD;
&#xD;
          -  Adequate bone marrow function of White Blood Cell (WBC) count to ≥ 1,500/uL; platelet&#xD;
             count ≥ 100,000/mm3; absolute neutrophil count (ANC) &gt; 1,200/uL&#xD;
&#xD;
          -  Patients must have adequate renal function by serum creatinine of ≤ 2.0 mg/dL.&#xD;
&#xD;
          -  Adequate hepatic function of bilirubin ≤ 2.5 mg/dL; SGOT/SGPT &lt; 3× upper limit of&#xD;
             normal (ULN).&#xD;
&#xD;
          -  Patients must have the required wash out periods from prior therapy:&#xD;
&#xD;
               -  Topical therapy: 2 weeks.&#xD;
&#xD;
               -  Chemotherapy and radiotherapy: 4 weeks.&#xD;
&#xD;
               -  Other investigational therapy: 4 weeks&#xD;
&#xD;
          -  Patients of reproductive potential and their partners must agree to use an effective&#xD;
             (&gt;90% reliability) form of contraception during the study and for 4 weeks following&#xD;
             the last study drug.&#xD;
&#xD;
          -  Women of reproductive potential must have a negative urine pregnancy test.&#xD;
&#xD;
          -  Patients should have a life expectancy of &gt; 6 months.&#xD;
&#xD;
          -  Patient should be able to comply with the treatment schedule and have the ability to&#xD;
             understand and willingness to sign the informed consent document.&#xD;
&#xD;
          -  Patients with manageable central nervous system metastases may be selected to this&#xD;
             trial. The CNS metastases are defined as manageable if there is no progression for at&#xD;
             least 4 weeks as determined by clinical examination and brain imaging (MRI and/or CT).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pre-existing autoimmune or antibody mediated disease including systemic lupus&#xD;
             erythematous, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune&#xD;
             thrombocytopenia, but excluding controlled thyroid disease, or the presence of&#xD;
             autoantibodies without clinical autoimmune disease.&#xD;
&#xD;
          -  Known history of human immunodeficiency virus (HIV) or any active immunosuppressive&#xD;
             systemic infection or a suppressed immune system, including acquired immuno-deficiency&#xD;
             syndrome (AIDS) or HIV positivity and known hepatitis infections (HCV or HBC), as&#xD;
             assessed by serology.&#xD;
&#xD;
          -  Patients on immunosuppressive therapy. Concurrent steroid use of not more than an&#xD;
             equivalent of 10 mg of prednisone is allowed.&#xD;
&#xD;
          -  Previous organ transplantation.&#xD;
&#xD;
          -  Patients with active infection or with a fever &gt;101°F (38.5°C) within 3 days prior to&#xD;
             the first scheduled treatment.&#xD;
&#xD;
          -  Concurrent participation in other treatment related clinical studies. Non-treatment&#xD;
             studies (e.g. observation or tumor cell analysis studies) are allowed.&#xD;
&#xD;
          -  Prior malignancy (active within 3 years of screening) except basal cell or completely&#xD;
             excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell&#xD;
             carcinoma of the cervix.&#xD;
&#xD;
             o Significant cardiovascular disease (i.e., New York Heart Association (NYHA) class 3&#xD;
             congestive heart failure; myocardial infarction within the past 6 months; unstable&#xD;
             angina; coronary angioplasty within the past 6 months; uncontrolled atrial or&#xD;
             ventricular cardiac arrhythmias).&#xD;
&#xD;
          -  Female patients who are pregnant or lactating.&#xD;
&#xD;
          -  Patients taken off Checkpoint Blockade agents: Ipilimumab, Nivolumab, Pembrolizumab,&#xD;
             for Grade 3 or greater autoimmune toxicity.&#xD;
&#xD;
          -  Patients who are positive for B-RafV600 mutation and are responding to targeted&#xD;
             therapy.&#xD;
&#xD;
          -  Any other medical history, including laboratory results, deemed by the investigator to&#xD;
             be likely to interfere with his/her participation in the study, or to interfere with&#xD;
             the interpretation of the results.&#xD;
&#xD;
          -  Patients with endocrinopathy greater than grade III.&#xD;
&#xD;
          -  Patients who have undergone a splenectomy in their previous medical history will be&#xD;
             excluded from this trial. Evidence of a splenectomy will be from history or records.&#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_contact>
    <last_name>Bruce Lyday</last_name>
    <phone>(714) 585-7485</phone>
    <email>bruce.lyday@primevax.com</email>
  </overall_contact>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>December 31, 2018</study_first_submitted>
  <study_first_submitted_qc>January 10, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 14, 2019</study_first_posted>
  <last_update_submitted>July 4, 2023</last_update_submitted>
  <last_update_submitted_qc>July 4, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 6, 2023</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>Melanoma</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/NCT03803397
org study id: PV001-001 (Arm 1)
nct id: NCT03803397
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Autologous monocyte-derived dendritic cells pulsed with tumor lysate (PV-001-DC) will be
      given to a group of 3 people. If this is found to be safe, it will be given to up to 7 other
      people, for a total of up to 10 people in this arm. This will be the first study of
      PV-001-DC.

      Eligible patients must be progressing after having completed prior therapy with a PD-1/PD-L1
      antagonist alone or in combination with anti-CTLA-4. If the patient is positive for BRAF, the
      patient must have progressed on at least one BRAF inhibitor in addition to a PD-1/PD-L1
      inhibitor alone or in combination with CTLA-4 for metastatic melanoma.

      Although other kinds of dendritic cells (DCs) have been approved to treat some forms of
      cancer, they have not been approved to treat melanoma. PV-001-DC is a special kind of DCs
      that is combined with tumor lysate. The study procedures will start with the removal of a
      small amount of tumor tissue processed into protein fragments (lysate). There will also be
      collection of white blood cells through apheresis (a procedure in which blood is drawn from a
      patient and separated into its different cell types), the white blood cells will be collected
      and the remainder returned to the patient. Dendritic cells will be grown from the collected
      white blood cells and combined with the lysate to form PV-001-DC.

      On the first day of study treatment, patients will go to the clinic and have a needle placed
      in a vein. The PV-001-DC product will be infused into the patient's vein. Approximately every
      3 weeks, for a total of 4 treatments, patients will receive additional infusions of
      PV-001-DC. Patients will be at the clinic for at least 1 hour following the end of the
      PV-001-DC infusion and if they feel fine, they may go home.

      Scans will be performed during the study at different times to see if their tumors have
      changed in size. Patients will also have their blood and small samples of tumors tested for
      changes to the immune system. After 365 days, the trial will be completed for that patient.

      Investigators will monitor patients carefully for any harmful side effects. The side effects
      in people cannot be completely known ahead of time
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence and severity of Treatment-Emergent Adverse Events
time frame: 365 days
description: Treatment-Emergent Adverse Event Incidence in patients receiving IV infusion of PV-001-DC
measure: Overall Response Rate (ORR)
time frame: 365 days
description: Tumor response will be measured per investigator's assessment according to RECIST v1.1 and iRECIST
measure: Progression-Free Survival (PFS)
time frame: 365 days
description: The length of time during the treatment of a disease, such as cancer, that a patient lives with the disease but it does not get worse, up to the end of the study
measure: Overall Survival (OS)
time frame: 365 days
description: Overall Survival is measured from the date of enrollment to the date of death for a dead patient. If a patient is still alive or is lost to follow up, the patient will be censored at the last contact date, up to the end of the study
arm group label: PV-001-DC alone
arm group type: Experimental
description: Autologous Monocyte-derived Lysate Pulsed Dendritic Cells
intervention type: Biological
intervention name: PV-001-DC
description: Patient-specific cellular therapeutic for cancer immunotherapy
arm group label: PV-001-DC alone
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bruce Lyday
phone: (714) 585-7485
email: bruce.lyday@primevax.com
responsible party type: Sponsor
mesh term: Melanoma
sharing ipd: No