<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/NCT04406623</url>
  </required_header>
  <id_info>
    <org_study_id>SL03-OHD-101</org_study_id>
    <nct_id>NCT04406623</nct_id>
  </id_info>
  <brief_title>Phase 1 Study of SL-172154 (SIRPα-Fc-CD40L) in Subjects With Ovarian Cancer</brief_title>
  <official_title>Phase 1 Dose Escalation Study of the Agonist Redirected Checkpoint, SL-172154 (SIRPα-Fc-CD40L) Administered Intravenously in Subjects With Ovarian Cancer</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 first in human, open label, multi-center, dose escalation study to evaluate&#xD;
      the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in&#xD;
      subjects with ovarian cancer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and&#xD;
      pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended&#xD;
      Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to&#xD;
      have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study&#xD;
      design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an&#xD;
      optional dose expansion cohort. In the dose escalation phase of the study, subjects will be&#xD;
      enrolled into sequential dose levels. The study may also enroll a pharmacodynamic cohort to&#xD;
      obtain additional pharmacodynamic data at one or more dose levels that have completed&#xD;
      evaluation for safety without exceeding the maximum tolerated dose (MTD). Subjects enrolled&#xD;
      in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion&#xD;
      cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity,&#xD;
      and pharmacodynamic data to inform the selection of a RP2D.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 29, 2020</start_date>
  <completion_date type="Actual">February 2, 2023</completion_date>
  <primary_completion_date type="Actual">February 2, 2023</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>Safety profile of SL-172154</measure>
    <time_frame>From Day 1 to 90 days after Last Dose 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</measure>
    <time_frame>From Day 1 to 90 days after Last Dose 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</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Establish the RP2D for SL-172154</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assess preliminary evidence of anti-tumor activity of SL-172154</measure>
    <time_frame>Approximately 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</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Number and proportion of participants with positive anti-drug antibody titer</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Maximum serum concentration (Cmax) of SL-172154</measure>
    <time_frame>Approximately 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>Minimum serum concentration (Cmin) of SL-172154</measure>
    <time_frame>Approximately 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>Time at which maximum concentration of SL-172154 is observed (Tmax)</measure>
    <time_frame>Approximately 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>Area under the serum concentration-time curve (AUC)</measure>
    <time_frame>Approximately 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)</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Terminal elimination half-life (t1/2) of SL-172154</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clearance (CL)</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Clearance of Sl-172154</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Volume of distribution</measure>
    <time_frame>Approximately 24 months</time_frame>
    <description>Volume of distribution of SL-172154</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">34</enrollment>
  <condition>Ovarian Cancer</condition>
  <condition>Fallopian Tube Cancer</condition>
  <condition>Primary Peritoneal Carcinoma</condition>
  <arm_group>
    <arm_group_label>SL-172154</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous administration</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>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;
          1. Subject has voluntarily agreed to participate by giving written informed consent in&#xD;
             accordance with ICH/GCP guidelines and applicable local regulations.&#xD;
&#xD;
          2. Subject must have a histologically confirmed diagnosis of an unresectable, locally&#xD;
             advanced or metastatic ovarian cancer, or primary peritoneal cancer or fallopian tube&#xD;
             cancer.&#xD;
&#xD;
          3. Subjects must be refractory or intolerant to existing therapy(ies) known to provide&#xD;
             clinical benefit for their condition. Subject must have received platinum-based&#xD;
             therapies, and should not be eligible for further platinum therapy, or should be&#xD;
             intolerant to such therapy. Subjects with HRD positive disease may participate if they&#xD;
             have received prior polyadenosine diphosphate ribose polymerase (PARP) inhibitor&#xD;
             therapy given alone or with bevacizumab.&#xD;
&#xD;
          4. Subjects should not be primary platinum refractory as defined by progressing during or&#xD;
             within 1 month of upfront platinum therapy.&#xD;
&#xD;
          5. Has measurable disease by RECIST v1.1 using radiologic assessment.&#xD;
&#xD;
          6. Subject age is 18 years and older.&#xD;
&#xD;
          7. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.&#xD;
&#xD;
          8. Has life expectancy of greater than 12 weeks.&#xD;
&#xD;
          9. Has adequate organ function.&#xD;
&#xD;
         10. Females of childbearing potential (FCBP) must have a negative serum or urine pregnancy&#xD;
             test within 72 hours of D1 of IP.&#xD;
&#xD;
         11. Recovery from prior anti-cancer treatments including surgery, radiotherapy,&#xD;
             chemotherapy or any other anti-cancer therapy to baseline or ≤ Grade 1.&#xD;
&#xD;
         12. Willing to consent to mandatory pre-treatment and on-treatment tumor biopsy(ies),&#xD;
             unless there is excessive risk as determined by the investigator.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants are excluded from the study if any of the following criteria apply:&#xD;
&#xD;
          1. Prior treatment with an anti-CD47 or anti-SIRPα targeting agent or a CD40 agonist.&#xD;
&#xD;
          2. Any anti-cancer therapy within the washout period prior to first dose (D1) of&#xD;
             SL-172154.&#xD;
&#xD;
          3. 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;
          4. Use of corticosteroids or other immunosuppressive medication, current or within 14&#xD;
             days of D1 of SL-172154 treatment.&#xD;
&#xD;
          5. Receipt of live attenuated vaccine within 28 days of D1 of IP.&#xD;
&#xD;
          6. Active or documented history of autoimmune disease. Exceptions include controlled Type&#xD;
             I diabetes, vitiligo, alopecia areata or hypo/hyperthyroidism.&#xD;
&#xD;
          7. 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;
          8. Active pneumonitis (i.e. drug-induced, idiopathic pulmonary fibrosis,&#xD;
             radiation-induced, etc.).&#xD;
&#xD;
          9. Ongoing or active infection (e.g., no systemic antimicrobial therapy for treatment of&#xD;
             infection within 5 days of D1 of IP).&#xD;
&#xD;
         10. 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;
         11. Clinically significant or uncontrolled cardiac/thromboembolic disease.&#xD;
&#xD;
         12. Untreated central nervous system or leptomeningeal metastases.&#xD;
&#xD;
         13. Women who are breast feeding.&#xD;
&#xD;
         14. 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;
         15. 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;
         16. Has undergone allogeneic stem cell transplantation or organ transplantation.&#xD;
&#xD;
         17. Known history or positive test for human immunodeficiency virus, or positive test for&#xD;
             hepatitis B.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91016</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Midwest</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</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>Stephenson Cancer Center at Oklahoma University</name>
      <address>
        <city>Oklahoma City</city>
        <state>Oklahoma</state>
        <zip>73104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sarah Cannon Research Institute</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37203</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>START Mountain Region</name>
      <address>
        <city>West Valley City</city>
        <state>Utah</state>
        <zip>84119</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>May 19, 2020</study_first_submitted>
  <study_first_submitted_qc>May 22, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 28, 2020</study_first_posted>
  <last_update_submitted>May 16, 2023</last_update_submitted>
  <last_update_submitted_qc>May 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 18, 2023</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>Ovarian Neoplasms</mesh_term>
    <mesh_term>Carcinoma, Ovarian Epithelial</mesh_term>
    <mesh_term>Fallopian Tube Neoplasms</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/NCT04406623
org study id: SL03-OHD-101
nct id: NCT04406623
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1 first in human, open label, multi-center, dose escalation study to evaluate
      the safety, tolerability, PK, anti-tumor activity and pharmacodynamic effects of SL-172154 in
      subjects with ovarian cancer.
This Phase 1 trial will evaluate the safety, tolerability, pharmacokinetics, anti-tumor and
      pharmacodynamic effects of SL-172154 and identify the dose and schedule i.e., recommended
      Phase 2 dose for future development (RP2D). Subjects eligible for enrollment are required to
      have platinum-ineligible ovarian, fallopian tube, and primary peritoneal cancers. The study
      design consists of dose escalation cohorts, an optional pharmacodynamic cohort, and an
      optional dose expansion cohort. In the dose escalation phase of the study, subjects will be
      enrolled into sequential dose levels. The study may also enroll a 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). Subjects enrolled
      in the pharmacodynamic cohort will not inform dose escalation decisions. A dose expansion
      cohort may be opened to further characterize safety, tolerability, PK, anti-tumor activity,
      and pharmacodynamic data to inform the selection of a RP2D.
allocation: N/A
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Safety profile of SL-172154
time frame: From Day 1 to 90 days after Last Dose of SL-172154
description: Incidence of all treatment emergent adverse events
measure: Maximum Tolerated Dose (MTD) of SL-172154
time frame: From Day 1 to 90 days after Last Dose 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
time frame: Approximately 24 months
description: Establish the RP2D for SL-172154
measure: Assess preliminary evidence of anti-tumor activity of SL-172154
time frame: Approximately 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
time frame: Approximately 24 months
description: Number and proportion of participants with positive anti-drug antibody titer
measure: Maximum serum concentration (Cmax) of SL-172154
time frame: Approximately 24 months
description: The Cmax is the maximum observed serum concentration of SL-172154 following single and multiple doses
measure: Minimum serum concentration (Cmin) of SL-172154
time frame: Approximately 24 months
description: The Cmin is the minimum observed serum concentration of SL-172154 following single and multiple doses
measure: Time at which maximum concentration of SL-172154 is observed (Tmax)
time frame: Approximately 24 months
description: The Tmax is the time at which the maximum concentration of SL-172154 is observed following single and multiple doses
measure: Area under the serum concentration-time curve (AUC)
time frame: Approximately 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)
time frame: Approximately 24 months
description: Terminal elimination half-life (t1/2) of SL-172154
measure: Clearance (CL)
time frame: Approximately 24 months
description: Clearance of Sl-172154
measure: Volume of distribution
time frame: Approximately 24 months
description: Volume of distribution of SL-172154
arm group label: SL-172154
arm group type: Experimental
description: Intravenous administration
intervention type: Drug
intervention name: 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: Female
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: Ovarian Neoplasms
mesh term: Carcinoma, Ovarian Epithelial
mesh term: Fallopian Tube Neoplasms