<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/NCT03278665</url>
  </required_header>
  <id_info>
    <org_study_id>4SC-202-2-2017</org_study_id>
    <nct_id>NCT03278665</nct_id>
  </id_info>
  <brief_title>4SC-202 in Combination With Pembrolizumab in Patients Primary Refractory/Non-responding to Prior Anti-PD-1 Therapy</brief_title>
  <acronym>SENSITIZE</acronym>
  <official_title>An Open-label Phase Ib/II, Multi-center Study of 4SC-202 in Combination With Pembrolizumab in Patients With Unresectable Stage III/Metastatic Stage IV Cutaneous Melanoma Primary Refractory/Non-responding to Prior Anti-PD-1 Therapy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>4SC AG</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>4SC AG</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>
      Phase Ib/II open-label, multi-center study with a priming cycle of 4SC-202 to evaluate the&#xD;
      safety, tolerability and preliminary efficacy of combination treatment with 4SC-202 and&#xD;
      Pembrolizumab. A dose expansion cohort at the Recommended Phase Two Dose (RPTD) will be&#xD;
      added.&#xD;
&#xD;
      Adult patients with advanced (unresectable or metastatic) cutaneous melanoma primary&#xD;
      refractory or non-responding to anti-PD-1 therapy as most current systemic anti-cancer&#xD;
      therapy and for whom no standard therapy is available, will be enrolled. The last&#xD;
      administration of anti-PD-1 therapy must have been performed within 6 months prior to&#xD;
      screening.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 25, 2017</start_date>
  <completion_date type="Actual">February 2, 2022</completion_date>
  <primary_completion_date type="Actual">February 2, 2022</primary_completion_date>
  <phase>Phase 1/Phase 2</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 Adverse Events [Safety and Tolerability]</measure>
    <time_frame>Up to 114 weeks</time_frame>
    <description>Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective Response Rate (ORR)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>The Objective Response Rate (ORR) will be defined as the percentage of patients who have achieved a confirmed response of at least Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Best Overall Response (BOR)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>The Best Overall Response defined as the best among all confirmed overall responses (irCR is better than irPR is better than irSD)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease Control Rate (DCR)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>The Disease Control Rate (DCR) will be defined as the percentage of patients who have achieved a confirmed response of at least irCR or irPR or a response of irSD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of Response (DOR)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>Duration of response (DOR) is defined as the time from the first documentation of response to the date of disease progression. Patients who have no documented disease progression at the end of the study or who are lost to follow-up or who receive additional anti-neoplastic therapy after discontinuing 4SC-202 and Pembrolizumab will be censored at the date of their last extent of disease assessment or on the first date of additional therapy, respectively.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>The time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first). Patients who have not progressed while on study and have not died while on study will be censored at the last evaluable assessment date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Progression (TTP)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>The time from first dosing (C1D1) to first date of first observed progression. Patients who have not progressed while on study, have not died while on study or experienced a non-disease- related death will be censored at the last evaluable assessment date.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival (OS)</measure>
    <time_frame>Up to 102 weeks</time_frame>
    <description>The Overall Survival (OS) is defined as the time from first dosing (C1D1) to date of death from any cause. Patients who have not died while on study will be censored at the last evaluable assessment date</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Malignant Melanoma</condition>
  <arm_group>
    <arm_group_label>4SC-202 + Pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Single arm study of 4SC-202 in combination with Pembrolizumab</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>4SC-202 in combination with Pembrolizumab</intervention_name>
    <description>4SC-202 in combination with Pembrolizumab</description>
    <arm_group_label>4SC-202 + Pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Main Inclusion Criteria:&#xD;
&#xD;
          -  Patients with unresectable stage III or stage IV cutaneous melanoma, as per American&#xD;
             Joint Committee on Cancer (AJCC) (Version 8) staging system (must have been&#xD;
             histologically confirmed at least once during course of disease). Patients with&#xD;
             metastatic tumor of unknown primary site and histology of melanoma are eligible.&#xD;
&#xD;
          -  Patients must be primary refractory or non-responding to anti-PD-1 therapy (either as&#xD;
             monotherapy or in combination with Ipilimumab)&#xD;
&#xD;
          -  Measurable disease by computer tomography (CT) or Magnetic resonance imaging (MRI) per&#xD;
             immune-related response evaluation criteria in solid tumors (irRECIST) 1.1 criteria,&#xD;
             with longest diameter for non-nodal lesions ≥ 10 mm and ≥ 15 mm in short axis for&#xD;
             nodal lesions&#xD;
&#xD;
          -  At least one tumor site (either primary site or metastasis) must be accessible for&#xD;
             sequential biopsies and patient must consent to the 2 mandatory biopsies. This&#xD;
             requirement is not applicable for continuous dosing schedules and may be waived by the&#xD;
             sponsor in other individual cases.&#xD;
&#xD;
        Main Exclusion Criteria:&#xD;
&#xD;
          -  Patients who achieved a CR or PR, during or after prior anti-PD-1 mono- or&#xD;
             anti-CTLA-4/anti-PD-1 combination therapy&#xD;
&#xD;
          -  Patients with symptomatic brain metastases/central nervous system (CNS) involvement&#xD;
&#xD;
          -  Patients with inadequate organ function&#xD;
&#xD;
          -  Therapy with agents known to prolong the QT interval and increase the risk for&#xD;
             Torsades de Pointes&#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>Dirk Schadendorf, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Universitätsklinikum Essen</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Universitätsklinikum Essen</name>
      <address>
        <city>Essen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medizinische Hochschule Hannover</name>
      <address>
        <city>Hannover</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Heidelberg</name>
      <address>
        <city>Heidelberg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Klinikum der Universität München</name>
      <address>
        <city>München</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Tübingen</name>
      <address>
        <city>Tübingen</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Universitätsklinikum Würzburg</name>
      <address>
        <city>Würzburg</city>
        <country>Germany</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Istituto Nazionale Tumori Fondazione &quot;G. Pascale&quot;</name>
      <address>
        <city>Napoli</city>
        <country>Italy</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Germany</country>
    <country>Italy</country>
  </location_countries>
  <verification_date>February 2022</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>February 3, 2022</last_update_submitted>
  <last_update_submitted_qc>February 3, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cutaneous melanoma</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Melanoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <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/NCT03278665
org study id: 4SC-202-2-2017
nct id: NCT03278665
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Phase Ib/II open-label, multi-center study with a priming cycle of 4SC-202 to evaluate the
      safety, tolerability and preliminary efficacy of combination treatment with 4SC-202 and
      Pembrolizumab. A dose expansion cohort at the Recommended Phase Two Dose (RPTD) will be
      added.

      Adult patients with advanced (unresectable or metastatic) cutaneous melanoma primary
      refractory or non-responding to anti-PD-1 therapy as most current systemic anti-cancer
      therapy and for whom no standard therapy is available, will be enrolled. The last
      administration of anti-PD-1 therapy must have been performed within 6 months prior to
      screening.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Adverse Events [Safety and Tolerability]
time frame: Up to 114 weeks
description: Safety and tolerability of the combination of 4SC-202 and Pembrolizumab will be assessed from adverse events.
measure: Objective Response Rate (ORR)
time frame: Up to 102 weeks
description: The Objective Response Rate (ORR) will be defined as the percentage of patients who have achieved a confirmed response of at least Immune-related Complete Response (irCR) or Immune-related Partial Response (irPR)
measure: Best Overall Response (BOR)
time frame: Up to 102 weeks
description: The Best Overall Response defined as the best among all confirmed overall responses (irCR is better than irPR is better than irSD)
measure: Disease Control Rate (DCR)
time frame: Up to 102 weeks
description: The Disease Control Rate (DCR) will be defined as the percentage of patients who have achieved a confirmed response of at least irCR or irPR or a response of irSD
measure: Duration of Response (DOR)
time frame: Up to 102 weeks
description: Duration of response (DOR) is defined as the time from the first documentation of response to the date of disease progression. Patients who have no documented disease progression at the end of the study or who are lost to follow-up or who receive additional anti-neoplastic therapy after discontinuing 4SC-202 and Pembrolizumab will be censored at the date of their last extent of disease assessment or on the first date of additional therapy, respectively.
measure: Progression Free Survival (PFS)
time frame: Up to 102 weeks
description: The time from first dosing (C1D1) to date of first observed progression or death from any cause (whichever comes first). Patients who have not progressed while on study and have not died while on study will be censored at the last evaluable assessment date.
measure: Time to Progression (TTP)
time frame: Up to 102 weeks
description: The time from first dosing (C1D1) to first date of first observed progression. Patients who have not progressed while on study, have not died while on study or experienced a non-disease- related death will be censored at the last evaluable assessment date.
measure: Overall Survival (OS)
time frame: Up to 102 weeks
description: The Overall Survival (OS) is defined as the time from first dosing (C1D1) to date of death from any cause. Patients who have not died while on study will be censored at the last evaluable assessment date
arm group label: 4SC-202 + Pembrolizumab
arm group type: Experimental
description: Single arm study of 4SC-202 in combination with Pembrolizumab
intervention type: Drug
intervention name: 4SC-202 in combination with Pembrolizumab
description: 4SC-202 in combination with Pembrolizumab
arm group label: 4SC-202 + Pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Dirk Schadendorf, MD
role: Principal Investigator
affiliation: Universitätsklinikum Essen
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Germany
country: Italy
responsible party type: Sponsor
mesh term: Melanoma
mesh term: Pembrolizumab
sharing ipd: No