<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/NCT04460456</url>
  </required_header>
  <id_info>
    <org_study_id>SBT6050-101</org_study_id>
    <nct_id>NCT04460456</nct_id>
  </id_info>
  <brief_title>A Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced HER2 Expressing Solid Tumors</brief_title>
  <official_title>A Phase 1/1B, Open-Label, Dose Escalation and Expansion Study of SBT6050 Alone and in Combination With PD-1 Inhibitors in Subjects With Advanced Solid Tumors Expressing HER2</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Silverback Therapeutics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Silverback Therapeutics</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>
      A first-in-human (FIH) study using SBT6050 and SBT6050 in combination with PD-1 inhibitors in&#xD;
      HER2 expressing or amplified advanced malignancies&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study has 5 parts. Part 1 will evaluate the safety, tolerability, and activity of&#xD;
      escalating doses of SBT6050 to estimate the maximum tolerated dose (MTD) and determine the&#xD;
      dose recommended for Part 2. Part 2 of the study will further evaluate SBT6050 in select HER2&#xD;
      expressing or amplified advanced malignancies.&#xD;
&#xD;
      Part 3 will evaluate the safety, tolerability, and activity of escalating doses of SBT6050 in&#xD;
      combination with pembrolizumab to estimate the MTD and determine the dose recommended for&#xD;
      Part 4. Part 4 of the study will further evaluate SBT6050 in combination with pembrolizumab&#xD;
      in select HER2 expressing or amplified advanced malignancies.&#xD;
&#xD;
      Part 5 of the study will evaluate the safety, tolerability, and activity of SBT6050 in&#xD;
      combination with cemiplimab in select HER2 expressing or amplified advanced malignancies.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">July 27, 2020</start_date>
  <completion_date type="Anticipated">December 2022</completion_date>
  <primary_completion_date type="Anticipated">December 2022</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>The proportion of subjects experiencing dose limiting toxicities</measure>
    <time_frame>28 days</time_frame>
    <description>Part 1 and 3 only</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The incidence and severity of adverse events (AEs) and serious adverse events</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 1, 2, 3, 4, and 5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 2, 4, and 5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Duration of response, defined as the time from date of first response (CR or PR)</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 2, 4, and 5</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)</measure>
    <time_frame>2 years</time_frame>
    <description>Parts1 and 3 only</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response, defined as the time from date of first response (CR or PR)</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 1 and 3 only</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate, defined as CR, PR, or stable disease for at least 6 months</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 1, 2, 3, 4, and 5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimates of selected pharmacokinetics (PK ) parameters for SBT6050</measure>
    <time_frame>2 years</time_frame>
    <description>Cmax: Parts 1, 2, 3, 4, and 5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Estimates of selected pharmacokinetics (PK ) parameters for SBT6050</measure>
    <time_frame>2 years</time_frame>
    <description>AUC: Parts 1, 2, 3, 4, and 5</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of antidrug antibodies (ADA) to SBT6050</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 1 and 2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression free survival</measure>
    <time_frame>2 years</time_frame>
    <description>Parts 2, 4, and 5</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">58</enrollment>
  <condition>HER2 Positive Solid Tumors</condition>
  <arm_group>
    <arm_group_label>SBT6050 Monotherapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Escalating doses of SBT6050 in Part 1 followed by expansion in Part 2 at the recommended dose determined in Part 1.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SBT6050 and pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Escalating doses of SBT6050 in combination with pembrolizumab in Part 3 followed by expansion in Part 4 at the recommended dose determined in Part 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>SBT6050 and cemiplimab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>SBT6050</intervention_name>
    <description>Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2</description>
    <arm_group_label>SBT6050 Monotherapy</arm_group_label>
    <arm_group_label>SBT6050 and cemiplimab</arm_group_label>
    <arm_group_label>SBT6050 and pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>pembrolizumab</intervention_name>
    <description>400 mg IV</description>
    <arm_group_label>SBT6050 and pembrolizumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Cemiplimab</intervention_name>
    <description>350 mg IV</description>
    <arm_group_label>SBT6050 and cemiplimab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Locally advanced or metastatic HER2-expressing (IHC 2+ or 3+) or amplified solid tumor&#xD;
&#xD;
          -  Subjects must have received prior therapies known to confer clinical benefit (unless&#xD;
             ineligible or refused to receive)&#xD;
&#xD;
          -  Measurable disease per RECIST 1.1&#xD;
&#xD;
          -  Tumor lesion amenable for biopsy or able to provide tissue from biopsy within last 6&#xD;
             months&#xD;
&#xD;
          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
&#xD;
          -  Adequate hematologic, hepatic, and cardiac function&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  History of allergic reactions to certain components of SBT6050 or similar drugs&#xD;
&#xD;
          -  Untreated brain metastases&#xD;
&#xD;
          -  Active autoimmune disease or a documented history of autoimmune disease or syndrome&#xD;
&#xD;
          -  Human immunodeficiency virus infection, active hepatitis B infection or hepatitis C&#xD;
             infection&#xD;
&#xD;
          -  Additional protocol defined inclusion/exclusion criteria may apply.&#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>Naomi Hunder, MD</last_name>
    <role>Study Director</role>
    <affiliation>Silverback Therapeutics</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27708</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pittsburgh Medical Center Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute/Tennessee Oncology</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>MD Anderson Cancer Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The START Center for Cancer Care</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Macquarie University Hospital Clinical Trials Unit</name>
      <address>
        <city>Sydney</city>
        <state>New South Wales</state>
        <zip>2109</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Peter MacCallum Cancer Centre</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3000</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Breast Cancer Research Centre - WA</name>
      <address>
        <city>Nedlands</city>
        <state>Western Australia</state>
        <zip>6009</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Seoul National University Hospital</name>
      <address>
        <city>Seoul</city>
        <zip>03080</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Asan Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>05505</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Samsung Medical Center</name>
      <address>
        <city>Seoul</city>
        <zip>06351</zip>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
    <country>Korea, Republic of</country>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>July 6, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 7, 2020</study_first_posted>
  <last_update_submitted>June 27, 2022</last_update_submitted>
  <last_update_submitted_qc>June 27, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 30, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HER2</keyword>
  <keyword>ERBB2</keyword>
  <keyword>Immunotherapy</keyword>
  <keyword>Gastric Cancer</keyword>
  <keyword>Gastroesophageal junction</keyword>
  <keyword>Breast Cancer</keyword>
  <keyword>Triple Negative Breast Cancer</keyword>
  <keyword>Stomach Cancer</keyword>
  <keyword>Colorectal Cancer</keyword>
  <keyword>Gastrointestinal Cancer</keyword>
  <keyword>Non-Small Cell Lung Cancer</keyword>
  <keyword>Monoclonal antibody</keyword>
  <keyword>TLR8</keyword>
  <keyword>TLR8 agonist</keyword>
  <keyword>Antibody drug conjugate</keyword>
  <keyword>Biliary tract cancer</keyword>
  <keyword>Head and neck cancer</keyword>
  <keyword>Urothelial cancer</keyword>
  <keyword>Endometrial cancer</keyword>
  <keyword>Pembrolizumab</keyword>
  <keyword>Anti-PD-1 mAb</keyword>
  <keyword>Cemiplimab</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
    <mesh_term>Cemiplimab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>July 18, 2022</submitted>
    <submission_canceled>July 22, 2022</submission_canceled>
    <submitted>July 22, 2022</submitted>
    <returned>June 9, 2023</returned>
  </pending_results>
  <!-- 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/NCT04460456
org study id: SBT6050-101
nct id: NCT04460456
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
A first-in-human (FIH) study using SBT6050 and SBT6050 in combination with PD-1 inhibitors in
      HER2 expressing or amplified advanced malignancies
This study has 5 parts. Part 1 will evaluate the safety, tolerability, and activity of
      escalating doses of SBT6050 to estimate the maximum tolerated dose (MTD) and determine the
      dose recommended for Part 2. Part 2 of the study will further evaluate SBT6050 in select HER2
      expressing or amplified advanced malignancies.

      Part 3 will evaluate the safety, tolerability, and activity of escalating doses of SBT6050 in
      combination with pembrolizumab to estimate the MTD and determine the dose recommended for
      Part 4. Part 4 of the study will further evaluate SBT6050 in combination with pembrolizumab
      in select HER2 expressing or amplified advanced malignancies.

      Part 5 of the study will evaluate the safety, tolerability, and activity of SBT6050 in
      combination with cemiplimab in select HER2 expressing or amplified advanced malignancies.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: The proportion of subjects experiencing dose limiting toxicities
time frame: 28 days
description: Part 1 and 3 only
measure: The incidence and severity of adverse events (AEs) and serious adverse events
time frame: 2 years
description: Parts 1, 2, 3, 4, and 5
measure: Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)
time frame: 2 years
description: Parts 2, 4, and 5
measure: Duration of response, defined as the time from date of first response (CR or PR)
time frame: 2 years
description: Parts 2, 4, and 5
measure: Objective response rate, defined as confirmed Complete Response (CR) or Partial Response (PR)
time frame: 2 years
description: Parts1 and 3 only
measure: Duration of response, defined as the time from date of first response (CR or PR)
time frame: 2 years
description: Parts 1 and 3 only
measure: Disease control rate, defined as CR, PR, or stable disease for at least 6 months
time frame: 2 years
description: Parts 1, 2, 3, 4, and 5
measure: Estimates of selected pharmacokinetics (PK ) parameters for SBT6050
time frame: 2 years
description: Cmax: Parts 1, 2, 3, 4, and 5
measure: Estimates of selected pharmacokinetics (PK ) parameters for SBT6050
time frame: 2 years
description: AUC: Parts 1, 2, 3, 4, and 5
measure: Incidence of antidrug antibodies (ADA) to SBT6050
time frame: 2 years
description: Parts 1 and 2
measure: Progression free survival
time frame: 2 years
description: Parts 2, 4, and 5
arm group label: SBT6050 Monotherapy
arm group type: Experimental
description: Escalating doses of SBT6050 in Part 1 followed by expansion in Part 2 at the recommended dose determined in Part 1.
arm group label: SBT6050 and pembrolizumab
arm group type: Experimental
description: Escalating doses of SBT6050 in combination with pembrolizumab in Part 3 followed by expansion in Part 4 at the recommended dose determined in Part 3.
arm group label: SBT6050 and cemiplimab
arm group type: Experimental
description: SBT6050 in combination with cemiplimab in Part 5 at the recommended dose determined in Parts 1 and 3.
intervention type: Drug
intervention name: SBT6050
description: Escalating doses of SBT6050 in Part 1 and recommended dose in Part 2
arm group label: SBT6050 Monotherapy
arm group label: SBT6050 and cemiplimab
arm group label: SBT6050 and pembrolizumab
intervention type: Drug
intervention name: pembrolizumab
description: 400 mg IV
arm group label: SBT6050 and pembrolizumab
intervention type: Drug
intervention name: Cemiplimab
description: 350 mg IV
arm group label: SBT6050 and cemiplimab
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Naomi Hunder, MD
role: Study Director
affiliation: Silverback Therapeutics
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Australia
country: Korea, Republic of
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
mesh term: Pembrolizumab
mesh term: Cemiplimab
sharing ipd: No
submitted: July 18, 2022
submission canceled: July 22, 2022
submitted: July 22, 2022
returned: June 9, 2023