<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/NCT03254732</url>
  </required_header>
  <id_info>
    <org_study_id>POLARIS2016-002</org_study_id>
    <nct_id>NCT03254732</nct_id>
  </id_info>
  <brief_title>Study ADI-PEG 20 Plus Pembrolizumab in Advanced Solid Cancers</brief_title>
  <official_title>Phase 1B Study of ADI-PEG 20 Plus Pembrolizumab in Advanced Solid Cancers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Polaris Group</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Polaris Group</source>
  <oversight_info>
    <has_dmc>No</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 trial of ADI-PEG 20 (36 mg/m2) weekly in combination with&#xD;
      pembrolizumab (1 and 2 mg/kg or 200 mg) every three weeks. Assessment of safety and&#xD;
      tolerability of drug combination&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is an open-label, phase 1b trial of ADI-PEG 20 in combination with pembrolizumab in&#xD;
      subjects with advanced cancers. Dose escalation will occur using a 3 + 3 + 3 design.&#xD;
&#xD;
      The first subject in a dose escalation cohort must have had treatment with ADI-PEG 20 +&#xD;
      pembrolizumab with a week of follow up) before the next 2 subjects are enrolled. Thus&#xD;
      subjects 2 and 3 may be enrolled on day 8 if there is no dose limiting toxicity (DLT) in&#xD;
      subject 1. No additional delay is required between treating subjects 4 to 6 or 7 to 9 in an&#xD;
      expanded cohort. Before proceeding to the next cohort dose level, the first 3 eligible&#xD;
      subjects in each cohort will have received at least 21 days of treatment (i.e. at least 2 of&#xD;
      the expected 3 doses of ADI-PEG 20 + one dose of pembrolizumab).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Changing Corporate Priorities&#xD;
  </why_stopped>
  <start_date type="Actual">July 14, 2017</start_date>
  <completion_date type="Actual">February 25, 2020</completion_date>
  <primary_completion_date type="Actual">May 7, 2019</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>Number of Participants with Adverse Events as a Measure of Safety and Tolerability of ADI-PEG 20 in combination with Pembrolizumab in Advanced Solid Cancers</measure>
    <time_frame>Up to 36 months</time_frame>
    <description>Number of participants with treatment-related adverse events and severity this is graded by CTCAE and MedDRA for Coding</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with PFS with Combination ADI-PEG 20 and Pembro.</measure>
    <time_frame>Assessments ever 9 weeks for 12 months</time_frame>
    <description>Progression Free Survival determined by RECIST 1.1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants with RR with Combination ADI-PEG 20 and Pembro.</measure>
    <time_frame>Assessments ever 9 weeks for 12 months</time_frame>
    <description>Response Rate determined by RECIST 1.1</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Overall Survival</measure>
    <time_frame>12 months after end of treatment</time_frame>
    <description>Follow-Up by Phone or Clinic Visit</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">33</enrollment>
  <condition>Advanced Solid Cancers</condition>
  <arm_group>
    <arm_group_label>ADI-PEG 20</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This is a phase 1b, open label trial of ADI-PEG 20 (36 mg/m2) weekly in combination with pembrolizumab (1 and 2 mg/kg or 200 mg) every three weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ADI PEG20</intervention_name>
    <description>ADI is a recombinant protein cloned from M. hominis and produced in E. coli, and conjugated with PEG of 20,000 mw. Thus ADI-PEG 20 is an arginine degrading enzyme, ADI, coupled to PEG.</description>
    <arm_group_label>ADI-PEG 20</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Pembrolizumab</intervention_name>
    <description>Pembrolizumab is a PD-1 blocking antibody indicated in the USA for the treatment.</description>
    <arm_group_label>ADI-PEG 20</arm_group_label>
    <other_name>Keytruda®</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Select Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed diagnosis of advanced solid tumor.&#xD;
&#xD;
          2. Prior failure of a systemic treatment approved by the health authority in the country&#xD;
             where the study will be enrolling. Such subjects may also have been treated with&#xD;
             radiotherapy, local therapy or surgery.&#xD;
&#xD;
          3. Measurable disease using RECIST 1.1 criteria.&#xD;
&#xD;
          4. Age ≥ 18 years.&#xD;
&#xD;
        Select Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with history of another primary cancer, including co-existent second&#xD;
             malignancy, with the exception of: a) curatively resected non-melanoma skin cancer; b)&#xD;
             curatively treated cervical carcinoma in situ; or c) other primary solid tumor with no&#xD;
             known active disease present or in the opinion of the investigator will not affect&#xD;
             patient outcome.&#xD;
&#xD;
          2. Subjects who had been treated with ADI-PEG 20 previously.&#xD;
&#xD;
          3. History of seizure disorder not related to underlying cancer.&#xD;
&#xD;
          4. Known allergy to pegylated compounds.&#xD;
&#xD;
          5. Known allergy to E. coli drug products (such as GMCSF).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Facility National Cheng Kung University</name>
      <address>
        <city>Tainan</city>
        <zip>704</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>December 23, 2016</study_first_submitted>
  <study_first_submitted_qc>August 16, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>April 20, 2022</last_update_submitted>
  <last_update_submitted_qc>April 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 27, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_browse>
  <!-- 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/NCT03254732
org study id: POLARIS2016-002
nct id: NCT03254732
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a phase 1b, open label trial of ADI-PEG 20 (36 mg/m2) weekly in combination with
      pembrolizumab (1 and 2 mg/kg or 200 mg) every three weeks. Assessment of safety and
      tolerability of drug combination
This is an open-label, phase 1b trial of ADI-PEG 20 in combination with pembrolizumab in
      subjects with advanced cancers. Dose escalation will occur using a 3 + 3 + 3 design.

      The first subject in a dose escalation cohort must have had treatment with ADI-PEG 20 +
      pembrolizumab with a week of follow up) before the next 2 subjects are enrolled. Thus
      subjects 2 and 3 may be enrolled on day 8 if there is no dose limiting toxicity (DLT) in
      subject 1. No additional delay is required between treating subjects 4 to 6 or 7 to 9 in an
      expanded cohort. Before proceeding to the next cohort dose level, the first 3 eligible
      subjects in each cohort will have received at least 21 days of treatment (i.e. at least 2 of
      the expected 3 doses of ADI-PEG 20 + one dose of pembrolizumab).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability of ADI-PEG 20 in combination with Pembrolizumab in Advanced Solid Cancers
time frame: Up to 36 months
description: Number of participants with treatment-related adverse events and severity this is graded by CTCAE and MedDRA for Coding
measure: Number of Participants with PFS with Combination ADI-PEG 20 and Pembro.
time frame: Assessments ever 9 weeks for 12 months
description: Progression Free Survival determined by RECIST 1.1
measure: Number of Participants with RR with Combination ADI-PEG 20 and Pembro.
time frame: Assessments ever 9 weeks for 12 months
description: Response Rate determined by RECIST 1.1
measure: Overall Survival
time frame: 12 months after end of treatment
description: Follow-Up by Phone or Clinic Visit
arm group label: ADI-PEG 20
arm group type: Experimental
description: This is a phase 1b, open label trial of ADI-PEG 20 (36 mg/m2) weekly in combination with pembrolizumab (1 and 2 mg/kg or 200 mg) every three weeks.
intervention type: Drug
intervention name: ADI PEG20
description: ADI is a recombinant protein cloned from M. hominis and produced in E. coli, and conjugated with PEG of 20,000 mw. Thus ADI-PEG 20 is an arginine degrading enzyme, ADI, coupled to PEG.
arm group label: ADI-PEG 20
intervention type: Drug
intervention name: Pembrolizumab
description: Pembrolizumab is a PD-1 blocking antibody indicated in the USA for the treatment.
arm group label: ADI-PEG 20
other name: Keytruda®
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Taiwan
responsible party type: Sponsor
mesh term: Pembrolizumab