<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/NCT04502888</url>
  </required_header>
  <id_info>
    <org_study_id>SL03-OHD-102</org_study_id>
    <nct_id>NCT04502888</nct_id>
  </id_info>
  <brief_title>Ph1 Study of SL-172154 Administered Intratumorally in Subjects With Squamous Cell Carcinoma of the Head and Neck or Skin</brief_title>
  <official_title>Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L), Administered Intratumorally in Subjects With Cutaneous Squamous Cell Carcinoma or Squamous Cell Carcinoma of the Head and Neck</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shattuck Labs, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shattuck Labs, Inc.</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 1 open-label, multi-center, dose-escalation study to evaluate the safety, PK,&#xD;
      anti-tumor activity, and pharmacodynamic effects of SL-172154 administered by intratumoral&#xD;
      injection in subjects with cutaneous squamous cell carcinoma (CSCC) or squamous cell&#xD;
      carcinoma of the head and neck (SCCHN).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor&#xD;
      activity and pharmacodynamic effects of SL-172154 when administered as an intratumoral&#xD;
      injection (ITI) and identify the dose and schedule i.e., recommended Phase 2 dose (RP2D) for&#xD;
      future development. Eligible subjects must have unresectable or recurrent, locally advanced&#xD;
      or metastatic squamous cell carcinoma of the skin or head and neck, that is not amenable to&#xD;
      curative surgery or radiotherapy. The study design consists of four sequential&#xD;
      dose-escalation cohorts and an optional pharmacodynamic cohort to obtain additional&#xD;
      pharmacodynamic data at one or more dose levels that have completed evaluation for safety&#xD;
      without exceeding the maximum tolerated dose (MTD).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision&#xD;
  </why_stopped>
  <start_date type="Actual">September 17, 2020</start_date>
  <completion_date type="Actual">April 8, 2022</completion_date>
  <primary_completion_date type="Actual">April 8, 2022</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>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of all treatment emergent adverse events to inform the safety profile of SL-172154 when administered intratumorally</measure>
    <time_frame>From Day 1 to 90 days after last injection of SL-172154</time_frame>
    <description>Incidence of all treatment-emergent adverse events</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Maximum Tolerated Dose (MTD) of SL-172154 when administered intratumorally</measure>
    <time_frame>From Day 1 to 90 days after last injection of SL-172154</time_frame>
    <description>Defined based on the rate of dose limiting toxicities (DLTs)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Based on all data collected during dose-escalation and pharmacodynamic cohorts, including safety, tolerability, PK, anti-tumor activity and PD effects</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary evidence of anti-tumor activity of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Disease assessment per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunogenicity to SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Proportion of participants with positive anti-drug antibody titer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum observed concentration (Cmax) of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time at which the maximum concentration is observed (Tmax) of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Minimum observed concentration (Cmin) of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Area under the serum concentration time curve (AUC) of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Terminal elimination half-life (t1/2) of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Terminal elimination half-life (t1/2) of SL-172154</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL) of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Clearance of Sl-172154</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution of SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Volume of distribtion of SL-172154</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes from baseline in cell counts to assess pharmacodynamic biomarkers in blood prior to, on-treatment and following SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Circulating immune cells such as: T cells, B cells, natural killer (NK) cells, and myeloid cells and circulating chemokine and cytokine levels</description>
  </other_outcome>
  <other_outcome>
    <measure>Changes from baseline in cell counts to assess pharmacodynamic biomarkers in tumor tissue prior to, on-treatment and following SL-172154 when administered by intratumoral injection (ITI)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>Presence of SL-172154 in tumor tissue, changes in T cells subsets, B cells and macrophages and assessment of SL-172154 in the tumor tissue, CD47 and CD40 expression and Programmed cell death ligand 1 (PD-L1) expression</description>
  </other_outcome>
  <other_outcome>
    <measure>To estimate progression-free survival (PFS)</measure>
    <time_frame>Approximately 18-24 months</time_frame>
    <description>PFS: time from first dose to progression by RECIST v1.1 or death, whichever comes first</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Cutaneous Squamous Cell Carcinoma</condition>
  <condition>Squamous Cell Carcinoma of Head and Neck</condition>
  <arm_group>
    <arm_group_label>SL-172154</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intratumoral administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Drug: SL-172154</intervention_name>
    <description>The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.</description>
    <arm_group_label>SL-172154</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants are eligible to be included in the study only if all the following criteria&#xD;
        apply:&#xD;
&#xD;
          -  Subject has voluntarily agreed to participate by giving written informed consent in&#xD;
             accordance with ICH/GCP guidelines and applicable local regulations.&#xD;
&#xD;
          -  Subject must have a histologically confirmed diagnosis of an unresectable or&#xD;
             recurrent, locally advanced or metastatic cutaneous squamous cell carcinoma or&#xD;
             squamous cell carcinoma of the head and neck that is not amenable to curative surgery&#xD;
             or radiotherapy.&#xD;
&#xD;
          -  Subjects must have received, been intolerant to, or ineligible for standard&#xD;
             therapy(ies) known to provide clinical benefit for their condition.&#xD;
&#xD;
          -  Subject has measurable disease by RECIST v1.1 using radiologic assessment.&#xD;
&#xD;
          -  Subject has at least 1 tumor lesion measuring between 1-6cm that is cutaneous and/or&#xD;
             subcutaneous and/or nodal and is clinically accessible and safe for injection by&#xD;
             direct visualization, palpation or by ultrasound guidance. PD Cohort Subjects Only:&#xD;
             Must have a second lesion that is non-injected and is amenable to tumor biopsy&#xD;
             collection.&#xD;
&#xD;
          -  Subject age is 18 years and older.&#xD;
&#xD;
          -  Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
          -  Has life expectancy of greater than 12 weeks.&#xD;
&#xD;
          -  Has adequate organ function.&#xD;
&#xD;
          -  Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy&#xD;
             test within 72 hours of D1 of IP.&#xD;
&#xD;
          -  Male subjects of reproductive potential must use acceptable contraception.&#xD;
&#xD;
          -  Recovery from prior anti-cancer treatments including surgery, radiotherapy,&#xD;
             chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.&#xD;
&#xD;
          -  Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies) of&#xD;
             injected lesion (and non-injected lesion(s) for subjects enrolled in the PD cohort)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist.&#xD;
&#xD;
          -  Any anti-cancer therapy within the washout period prior to first dose (D1) of&#xD;
             SL-172154.&#xD;
&#xD;
          -  Concurrent chemotherapy, immunotherapy, biologic or hormonal/hormonal suppression&#xD;
             therapy for cancer treatment is prohibited. Concurrent use of hormones for non-cancer&#xD;
             related conditions is acceptable.&#xD;
&#xD;
          -  Use of corticosteroids or other immunosuppressive medication, current or within 14&#xD;
             days of D1 of SL-172154 treatment.&#xD;
&#xD;
          -  Receipt of live attenuated vaccine within 28 days of D1 of IP.&#xD;
&#xD;
          -  Hypersensitivity to the active drug substance or to any of the excipients for the&#xD;
             agent to be administered or subjects with known hypersensitivity to Chinese hamster&#xD;
             ovary cell products.&#xD;
&#xD;
          -  History of coagulopathy resulting in uncontrolled bleeding, eg, hemophilia, von&#xD;
             Willebrand's disease.&#xD;
&#xD;
          -  Requires continuous anticoagulation therapy or antiplatelet therapy&#xD;
&#xD;
          -  Active or documented history of autoimmune disease. Exceptions include controlled Type&#xD;
             I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.&#xD;
&#xD;
          -  Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis,&#xD;
             radiation-induced, etc.).&#xD;
&#xD;
          -  Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of&#xD;
             infection within 5 days of D1 of IP).&#xD;
&#xD;
          -  Symptomatic peptic ulcer disease or gastritis, active diverticulitis, other serious&#xD;
             gastrointestinal disease associated with diarrhea within 6 months of D1 of IP.&#xD;
&#xD;
          -  Clinically significant or uncontrolled cardiac/thromboembolic disease.&#xD;
&#xD;
          -  Untreated central nervous system or leptomeningeal metastases.&#xD;
&#xD;
          -  Women who are breastfeeding.&#xD;
&#xD;
          -  Psychiatric illness/social circumstances that would limit compliance with study&#xD;
             requirements and substantially increase the risk of AEs or compromised ability to&#xD;
             provide written informed consent.&#xD;
&#xD;
          -  Another malignancy that requires active therapy and that in the opinion of the&#xD;
             investigator and Sponsor would interfere with monitoring of radiologic assessments of&#xD;
             response to IP.&#xD;
&#xD;
          -  Has undergone allogeneic stem cell transplantation or organ transplantation.&#xD;
&#xD;
          -  Known history or positive test for human immunodeficiency virus, or positive test for&#xD;
             hepatitis B.&#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>University of California, Los Angeles</name>
      <address>
        <city>Los Angeles</city>
        <state>California</state>
        <zip>90095</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dana-Farber Cancer Institute</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina at Chapel Hill</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>UPMC Hillman Cancer Center</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15232</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_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>July 31, 2020</study_first_submitted>
  <study_first_submitted_qc>August 4, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>December 6, 2022</last_update_submitted>
  <last_update_submitted_qc>December 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>intratumoral injection</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Carcinoma</mesh_term>
    <mesh_term>Carcinoma, Squamous Cell</mesh_term>
    <mesh_term>Squamous Cell Carcinoma of Head and Neck</mesh_term>
  </condition_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/NCT04502888
org study id: SL03-OHD-102
nct id: NCT04502888
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1 open-label, multi-center, dose-escalation study to evaluate the safety, PK,
      anti-tumor activity, and pharmacodynamic effects of SL-172154 administered by intratumoral
      injection in subjects with cutaneous squamous cell carcinoma (CSCC) or squamous cell
      carcinoma of the head and neck (SCCHN).
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor
      activity and pharmacodynamic effects of SL-172154 when administered as an intratumoral
      injection (ITI) and identify the dose and schedule i.e., recommended Phase 2 dose (RP2D) for
      future development. Eligible subjects must have unresectable or recurrent, locally advanced
      or metastatic squamous cell carcinoma of the skin or head and neck, that is not amenable to
      curative surgery or radiotherapy. The study design consists of four sequential
      dose-escalation cohorts and an optional pharmacodynamic cohort to obtain additional
      pharmacodynamic data at one or more dose levels that have completed evaluation for safety
      without exceeding the maximum tolerated dose (MTD).
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of all treatment emergent adverse events to inform the safety profile of SL-172154 when administered intratumorally
time frame: From Day 1 to 90 days after last injection of SL-172154
description: Incidence of all treatment-emergent adverse events
measure: Maximum Tolerated Dose (MTD) of SL-172154 when administered intratumorally
time frame: From Day 1 to 90 days after last injection of SL-172154
description: Defined based on the rate of dose limiting toxicities (DLTs)
measure: Establish the recommended Phase 2 dose (RP2D) for SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Based on all data collected during dose-escalation and pharmacodynamic cohorts, including safety, tolerability, PK, anti-tumor activity and PD effects
measure: Assess preliminary evidence of anti-tumor activity of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Disease assessment per investigator assessment according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v 1.1)
measure: Immunogenicity to SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Proportion of participants with positive anti-drug antibody titer
measure: Maximum observed concentration (Cmax) of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
measure: Time at which the maximum concentration is observed (Tmax) of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
measure: Minimum observed concentration (Cmin) of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses
measure: Area under the serum concentration time curve (AUC) of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: The AUC is the area under the serum concentration time curve following single and multiple doses of SL-172154
measure: Terminal elimination half-life (t1/2) of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Terminal elimination half-life (t1/2) of SL-172154
measure: Clearance (CL) of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Clearance of Sl-172154
measure: Volume of distribution of SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Volume of distribtion of SL-172154
measure: Changes from baseline in cell counts to assess pharmacodynamic biomarkers in blood prior to, on-treatment and following SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Circulating immune cells such as: T cells, B cells, natural killer (NK) cells, and myeloid cells and circulating chemokine and cytokine levels
measure: Changes from baseline in cell counts to assess pharmacodynamic biomarkers in tumor tissue prior to, on-treatment and following SL-172154 when administered by intratumoral injection (ITI)
time frame: Approximately 18-24 months
description: Presence of SL-172154 in tumor tissue, changes in T cells subsets, B cells and macrophages and assessment of SL-172154 in the tumor tissue, CD47 and CD40 expression and Programmed cell death ligand 1 (PD-L1) expression
measure: To estimate progression-free survival (PFS)
time frame: Approximately 18-24 months
description: PFS: time from first dose to progression by RECIST v1.1 or death, whichever comes first
arm group label: SL-172154
arm group type: Experimental
description: Intratumoral administration
intervention type: Drug
intervention name: Drug: SL-172154
description: The investigational product (IP), SL-172154, is a novel fusion protein consisting of human SIRPα and CD40L (SIRPα -Fc-CD40L) linked via a human Fc.
arm group label: SL-172154
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Carcinoma
mesh term: Carcinoma, Squamous Cell
mesh term: Squamous Cell Carcinoma of Head and Neck