<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/NCT03773744</url>
  </required_header>
  <id_info>
    <org_study_id>Ad/MG1-MAGEA3-003</org_study_id>
    <nct_id>NCT03773744</nct_id>
  </id_info>
  <brief_title>MG1-MAGEA3 With Ad-MAGEA3 and Pembrolizumab in Patients With Previously Treated Metastatic Melanoma or Cutaneous Squamous Cell Carcinoma</brief_title>
  <acronym>Pelican</acronym>
  <official_title>A Phase 1b, Multicenter, Open-label Trial of Oncolytic MG1 Expressing MAGE-A3 (MG1-MAGEA3) With Adenovirus Vaccine Expressing MAGE-A3 (Ad-MAGEA3), in Combination With Immune Modulating Therapy in Patients With Metastatic Melanoma or Previously Treated Cutaneous Squamous Cell Carcinoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Turnstone Biologics, Corp.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Turnstone Biologics, Corp.</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>
      This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in&#xD;
      patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed&#xD;
      prior standard of care treatments. Upon determination of a Maximum Tolerated Dose (MTD) or&#xD;
      Maximum Feasible Dose (MFD) the study will be expanded into up to 24 additional Metastatic&#xD;
      Melanoma patients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in&#xD;
      patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed&#xD;
      prior standard of care treatments. This study will consist of two arms where the dose will be&#xD;
      increased independently until the maximum tolerated dose (MTD) / maximum feasible dose (MFD)&#xD;
      is reached.&#xD;
&#xD;
      Arm 1 - Low-dose cyclophosphamide, followed by an Ad-MAGEA3 intramuscular (IM) prime,&#xD;
      followed by intravenous (IV) administration of MG1-MAGEA3 and IV pembrolizumab.&#xD;
&#xD;
      Arm 2 - Ad-MAGEA3 IM injection as a prime, followed by IV administration of MG1-MAGEA3,&#xD;
      followed by intratumoral (IT) injection of MG1-MAGEA3 into tumors and IV pembrolizumab.&#xD;
&#xD;
      In the Phase 1b Expansion for each arm, additional patients will be enrolled at the MTD/MDF&#xD;
      as determined in Phase 1 in order to more thoroughly explore immune response,&#xD;
      pharmacokinetics/dynamics, and safety for Malignant Melanoma patients who have failed&#xD;
      standard therapies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    insufficient suitable drug supply&#xD;
  </why_stopped>
  <start_date type="Actual">February 15, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">October 30, 2020</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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma</measure>
    <time_frame>6 months</time_frame>
    <description>Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 5.0</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma</measure>
    <time_frame>5 weeks</time_frame>
    <description>MTD/MFD of Ad/MG1-MAGEA3 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Evaluate Overall Response</measure>
    <time_frame>2 years</time_frame>
    <description>Determine the overall response rate (Partial Response (PR) + Complete Response (CR))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate Disease Control</measure>
    <time_frame>2 years</time_frame>
    <description>Determine Disease Control Rate (PR+CR+Stable Disease (SD))</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate PFS</measure>
    <time_frame>2 years</time_frame>
    <description>Progression free survival in months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Evaluate Duration of Response, if any</measure>
    <time_frame>2 years</time_frame>
    <description>Duration of Response (CR, PR, SD) in months</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Metastatic Melanoma</condition>
  <condition>Squamous Cell Skin Carcinoma</condition>
  <arm_group>
    <arm_group_label>Arm 1: Intravenous Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Low dose cyclophosphamide (300mg/ m2) at Day -3, then a fixed dose of Ad-MAGEA3 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-MAGEA3 administered as 2 intravenous (IV) doses at Day 15 and Day 18 and fixed dose pembrolizumab (200mg) beginning at either Week 6 or Day 1, depending on the cohort.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm 2: Intravenous followed by Intratumoral Dosing</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A fixed dose of Ad-MAGEA3 administered IM followed by Pembrolizumab on Day 1. MG1-MAGEA3 administered as an intravenous (IV) dose at Day 15, followed by intratumoral (IT) MG1-MAGEA3 on Day 22, Day 29, and Day 36. IT MG1-MAGEA3 booster injections may be continued every 3 weeks beginning at Day 43 (Week 6).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ad-MAGEA3</intervention_name>
    <description>Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen</description>
    <arm_group_label>Arm 1: Intravenous Dosing</arm_group_label>
    <arm_group_label>Arm 2: Intravenous followed by Intratumoral Dosing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>MG1-MAGEA3</intervention_name>
    <description>MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen</description>
    <arm_group_label>Arm 1: Intravenous Dosing</arm_group_label>
    <arm_group_label>Arm 2: Intravenous followed by Intratumoral Dosing</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>monoclonal antibody; checkpoint inhibitor of PD1</description>
    <arm_group_label>Arm 1: Intravenous Dosing</arm_group_label>
    <arm_group_label>Arm 2: Intravenous followed by Intratumoral Dosing</arm_group_label>
    <other_name>Keytruda</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cyclophosphamide</intervention_name>
    <description>low-dose chemotherapy</description>
    <arm_group_label>Arm 1: Intravenous Dosing</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Have histologically or cytologically confirmed diagnosis of locally advanced&#xD;
             metastatic melanoma or cutaneous squamous cell carcinoma that has failed standard&#xD;
             therapies&#xD;
&#xD;
          -  For patients treated intratumorally, must have a lesion suitable for direct injection&#xD;
             of MG1-MAGEA3&#xD;
&#xD;
          -  Have at least one tumor amenable to biopsy&#xD;
&#xD;
          -  Have measurable disease via RECIST 1.1 criteria&#xD;
&#xD;
          -  Adequate organ function and performance status&#xD;
&#xD;
          -  Additional inclusion criteria present&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with any MAGE-A3 vaccine immunotherapy&#xD;
&#xD;
          -  Prior systemic therapy for cancer within 4 weeks (8 weeks for lung radiation), and has&#xD;
             recovered from chemo-related toxicities to Grade 1 or less&#xD;
&#xD;
          -  Intolerant to prior PD1/PD-L1 therapy&#xD;
&#xD;
          -  Requires use of anti-platelet or anti-coagulant therapy that cannot be safely&#xD;
             suspended for per protocol biopsies or intra-tumoral injections.&#xD;
&#xD;
          -  Known active CNS metastases and/or carcinomatous meningitis.&#xD;
&#xD;
          -  Active autoimmune disease that has required systemic therapy in the past 2 years.&#xD;
&#xD;
          -  Conditions likely to have resulted in splenic dysfunction.&#xD;
&#xD;
          -  Known HIV/AIDS, active HBV or HCV infection.&#xD;
&#xD;
          -  Additional Exclusion criteria exist&#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>Steve Bernstein, MD</last_name>
    <role>Study Director</role>
    <affiliation>Turnstone Biologics</affiliation>
  </overall_official>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 11, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>April 1, 2021</last_update_submitted>
  <last_update_submitted_qc>April 1, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 6, 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>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cyclophosphamide</mesh_term>
    <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>


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/NCT03773744
org study id: Ad/MG1-MAGEA3-003
nct id: NCT03773744
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in
      patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed
      prior standard of care treatments. Upon determination of a Maximum Tolerated Dose (MTD) or
      Maximum Feasible Dose (MFD) the study will be expanded into up to 24 additional Metastatic
      Melanoma patients.
This is a Phase 1b open-label dose escalation trial of Ad/MG1-MAGEA3 and Pembrolizumab in
      patients with Metastatic Melanoma or Cutaneous Squamous Cell Skin Cancer that has failed
      prior standard of care treatments. This study will consist of two arms where the dose will be
      increased independently until the maximum tolerated dose (MTD) / maximum feasible dose (MFD)
      is reached.

      Arm 1 - Low-dose cyclophosphamide, followed by an Ad-MAGEA3 intramuscular (IM) prime,
      followed by intravenous (IV) administration of MG1-MAGEA3 and IV pembrolizumab.

      Arm 2 - Ad-MAGEA3 IM injection as a prime, followed by IV administration of MG1-MAGEA3,
      followed by intratumoral (IT) injection of MG1-MAGEA3 into tumors and IV pembrolizumab.

      In the Phase 1b Expansion for each arm, additional patients will be enrolled at the MTD/MDF
      as determined in Phase 1 in order to more thoroughly explore immune response,
      pharmacokinetics/dynamics, and safety for Malignant Melanoma patients who have failed
      standard therapies.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety of Ad/MG1-MAGEA3 administration in Melanoma or Squamous Cell Skin Carcinoma
time frame: 6 months
description: Safety will be determined by assessing the severity and frequency of treatment emergent Adverse Events and clinical laboratory toxicity using NCI CTCAE v 5.0
measure: Determine the maximum tolerated dose (MTD)/ maximum feasible dose (MFD) of Ad/MG1-MAGEA3 in Melanoma or Squamous Cell Skin Carcinoma
time frame: 5 weeks
description: MTD/MFD of Ad/MG1-MAGEA3 administered by IV infusion alone and IV infusion followed by direct injection of tumor (IT injection) in Melanoma or Squamous Cell Skin Carcinoma
measure: Evaluate Overall Response
time frame: 2 years
description: Determine the overall response rate (Partial Response (PR) + Complete Response (CR))
measure: Evaluate Disease Control
time frame: 2 years
description: Determine Disease Control Rate (PR+CR+Stable Disease (SD))
measure: Evaluate PFS
time frame: 2 years
description: Progression free survival in months
measure: Evaluate Duration of Response, if any
time frame: 2 years
description: Duration of Response (CR, PR, SD) in months
arm group label: Arm 1: Intravenous Dosing
arm group type: Experimental
description: Low dose cyclophosphamide (300mg/ m2) at Day -3, then a fixed dose of Ad-MAGEA3 administered IM on study Day 1. Followed by one of 3 dose levels (escalation) of MG1-MAGEA3 administered as 2 intravenous (IV) doses at Day 15 and Day 18 and fixed dose pembrolizumab (200mg) beginning at either Week 6 or Day 1, depending on the cohort.
arm group label: Arm 2: Intravenous followed by Intratumoral Dosing
arm group type: Experimental
description: A fixed dose of Ad-MAGEA3 administered IM followed by Pembrolizumab on Day 1. MG1-MAGEA3 administered as an intravenous (IV) dose at Day 15, followed by intratumoral (IT) MG1-MAGEA3 on Day 22, Day 29, and Day 36. IT MG1-MAGEA3 booster injections may be continued every 3 weeks beginning at Day 43 (Week 6).
intervention type: Drug
intervention name: Ad-MAGEA3
description: Adenovirus vaccine expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
arm group label: Arm 1: Intravenous Dosing
arm group label: Arm 2: Intravenous followed by Intratumoral Dosing
intervention type: Drug
intervention name: MG1-MAGEA3
description: MG1 Maraba oncolytic virus expressing Melanoma-associated antigen 3 (MAGEA3), a tumor antigen
arm group label: Arm 1: Intravenous Dosing
arm group label: Arm 2: Intravenous followed by Intratumoral Dosing
intervention type: Drug
intervention name: Pembrolizumab
description: monoclonal antibody; checkpoint inhibitor of PD1
arm group label: Arm 1: Intravenous Dosing
arm group label: Arm 2: Intravenous followed by Intratumoral Dosing
other name: Keytruda
intervention type: Drug
intervention name: Cyclophosphamide
description: low-dose chemotherapy
arm group label: Arm 1: Intravenous Dosing
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Steve Bernstein, MD
role: Study Director
affiliation: Turnstone Biologics
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Melanoma
mesh term: Carcinoma, Squamous Cell
mesh term: Cyclophosphamide
mesh term: Pembrolizumab
sharing ipd: No