<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/NCT03834662</url>
  </required_header>
  <id_info>
    <org_study_id>AVID200-03</org_study_id>
    <nct_id>NCT03834662</nct_id>
  </id_info>
  <brief_title>A Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients Malignancies</brief_title>
  <official_title>A Phase 1 Cohort Dose-Escalation Trial of AVID200, a Transforming Growth Factor β (TGFβ) Inhibitor, in Patients With Advanced or Metastatic Solid Tumor Malignancies</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Formation Biologics</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Formation Biologics</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>
      TGFβ has profound local immunosuppressive and immunoexclusion effects in the tumor&#xD;
      microenvironment that are integrally involved in the failure of immune checkpoint inhibitors&#xD;
      in some tumors. Preclinical data in a variety of models strongly support the study of AVID200&#xD;
      in patients with treatment-refractory advanced and metastatic malignancies as an approach to&#xD;
      reducing immunosuppression/exclusion and increasing the activity of immune checkpoint&#xD;
      inhibitors.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      TGFβ inhibits local anti-tumor immunity in the tumor microenvironment (TME) and also promotes&#xD;
      the epithelial to mesenchymal transition (EMT) that enhances the metastatic potential of&#xD;
      tumor cells. Cancer-associated fibroblasts (CAFs) are a critical constituent of the TME. As&#xD;
      is the case for fibrosis in other settings, these cells are myofibroblast-like, and respond&#xD;
      to and are activated by tumor-derived TGFβ. CAFs play a critical role in promoting EMT&#xD;
      resulting in increased tumor cell migration and invasion as well as maintaining the TME to&#xD;
      support tumor cell survival. The immunosuppressive role of TGFβ in the TME has been clearly&#xD;
      demonstrated with the activation of CAFs being an important mechanism underlying immune cell&#xD;
      exclusion. Exclusion of immune cells from tumors and local immunosuppression can both be&#xD;
      reversed by AVID200 therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Anticipated">December 30, 2020</completion_date>
  <primary_completion_date type="Actual">February 19, 2020</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>Sequential Assignment</intervention_model>
    <intervention_model_description>Evaluation of the safety, tolerability, and dose-limiting toxicities (DLTs), to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of AVID200 when administered once every 3 weeks (Q3W) by IV infusion to patient cohorts (3)</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of Treatment-Emergent Adverse Events</measure>
    <time_frame>From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, for up to 24 months</time_frame>
    <description>Number of participants with treatment-related adverse events as assessed by CTCAE v5.0</description>
  </primary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Malignant Solid Tumor</condition>
  <arm_group>
    <arm_group_label>Dose Level 1: 180 mg/m2 of AVID200</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous infusion of AVID200 over 1 hour administered every three weeks. Starting dose for dose escalation.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 2: 550 mg/m2 of AVID200</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous infusion of AVID200 over 1 hour administered every three weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dose Level 3: 1100 mg/m2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Intravenous infusion of AVID200 over 1.5 hours administered every three weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>AVID200</intervention_name>
    <description>A TGFβ receptor ectodomain-IgG Fc fusion protein inhibitor of TGFβ</description>
    <arm_group_label>Dose Level 1: 180 mg/m2 of AVID200</arm_group_label>
    <arm_group_label>Dose Level 2: 550 mg/m2 of AVID200</arm_group_label>
    <arm_group_label>Dose Level 3: 1100 mg/m2</arm_group_label>
    <other_name>TGFβ receptor ectodomain-IgG Fc fusion protein</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients with a documented (histologically or cytologically proven) solid tumor&#xD;
             malignancy that is locally advanced or metastatic&#xD;
&#xD;
          -  Patients with a malignancy that is currently not amenable to surgical intervention due&#xD;
             to either medical contraindications or non-resectability of the tumor&#xD;
&#xD;
          -  Patients with a malignancy that is either refractory to, or the patient is intolerant&#xD;
             of existing therapy(ies) known to provide clinical benefit, or for which no standard&#xD;
             therapy is available&#xD;
&#xD;
          -  Patients with measurable or non-measurable disease according to RECIST, v1.1&#xD;
&#xD;
          -  Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of&#xD;
             0 or 1 (or equivalent Karnofsky PS), and anticipated life expectancy of ≥ 3 months&#xD;
&#xD;
          -  Patients and their partners who are either not of childbearing potential or who agree&#xD;
             to use a highly effective, non-hormonal, method of contraception during the study and&#xD;
             continuing until 4 months after the last dose of study drug); male patients agreeing&#xD;
             to refrain from sperm donation during this period.&#xD;
&#xD;
          -  Patients with the ability to understand and give written informed consent for&#xD;
             participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with an active second malignancy or history of another malignancy within the&#xD;
             last 2 years with the exception of:&#xD;
&#xD;
               -  Treated non-melanoma skin cancers&#xD;
&#xD;
               -  Treated carcinoma in situ (CIS) of the breast, cervix, bladder, colon,&#xD;
                  endometrium, skin (melanoma) provided complete response (CR) was achieved at&#xD;
                  least 2 years prior to study and no additional therapy is ongoing or required&#xD;
                  during study period with the exception of anti-estrogen/androgen therapy or&#xD;
                  bisphosphonates&#xD;
&#xD;
               -  Controlled, superficial carcinoma of the bladder&#xD;
&#xD;
               -  T1a carcinoma of the prostate comprising &lt; 5% of resected tissue and prostate&#xD;
                  specific antigen (PSA) within normal limits (WNL) since resection&#xD;
&#xD;
          -  Any antineoplastic agent for the primary malignancy (standard or investigational),&#xD;
             without delayed toxicity, within 4 weeks or 5 plasma half-lives, whichever is&#xD;
             shortest, prior to C1/D1 and during study with the exception of:&#xD;
&#xD;
             -Nitrosoureas and mitomycin C within 6 weeks prior to C1/D1 and during study&#xD;
&#xD;
          -  Any other investigational treatments within 4 weeks prior to and during study;&#xD;
             includes participation in any medical device or supportive care therapeutic&#xD;
             intervention trials&#xD;
&#xD;
          -  Radiotherapy for target lesions within 4 weeks prior to C1/D1 and during study;&#xD;
             radiotherapy for non-target lesions within 2 weeks prior to C1/D1&#xD;
&#xD;
          -  Radiotherapy within 2 weeks prior to C1/D1 and during study. Patients must have&#xD;
             recovered from all radiation-related toxicities, not require corticosteroids, and not&#xD;
             have had radiation pneumonitis.&#xD;
&#xD;
          -  Use of live vaccines against infectious diseases 4 weeks prior to C1/D1 and during&#xD;
             study&#xD;
&#xD;
          -  Immunosuppressive or systemic hormonal therapy (&gt; 10 mg daily prednisone or&#xD;
             equivalent) within 2 weeks prior to C1/D1 and during study&#xD;
&#xD;
          -  Prophylactic use of hematopoietic growth factors within 2 weeks prior to C1/D1 and&#xD;
             during Cycle 1 of study; thereafter prophylactic use of growth factors is allowed as&#xD;
             clinically indicated&#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>Paul I Nadler, MD</last_name>
    <role>Study Director</role>
    <affiliation>Forbius (Formation Biologics)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>START Midwest Clinic</name>
      <address>
        <city>Grand Rapids</city>
        <state>Michigan</state>
        <zip>49546</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>Princess Margaret Cancer Centre</name>
      <address>
        <city>Toronto</city>
        <zip>M5G 1Z5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2020</verification_date>
  <study_first_submitted>January 31, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 8, 2019</study_first_posted>
  <last_update_submitted>December 17, 2020</last_update_submitted>
  <last_update_submitted_qc>December 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">December 19, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Solid tumors</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Neoplasms</mesh_term>
  </condition_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/NCT03834662
org study id: AVID200-03
nct id: NCT03834662
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
TGFβ has profound local immunosuppressive and immunoexclusion effects in the tumor
      microenvironment that are integrally involved in the failure of immune checkpoint inhibitors
      in some tumors. Preclinical data in a variety of models strongly support the study of AVID200
      in patients with treatment-refractory advanced and metastatic malignancies as an approach to
      reducing immunosuppression/exclusion and increasing the activity of immune checkpoint
      inhibitors.
TGFβ inhibits local anti-tumor immunity in the tumor microenvironment (TME) and also promotes
      the epithelial to mesenchymal transition (EMT) that enhances the metastatic potential of
      tumor cells. Cancer-associated fibroblasts (CAFs) are a critical constituent of the TME. As
      is the case for fibrosis in other settings, these cells are myofibroblast-like, and respond
      to and are activated by tumor-derived TGFβ. CAFs play a critical role in promoting EMT
      resulting in increased tumor cell migration and invasion as well as maintaining the TME to
      support tumor cell survival. The immunosuppressive role of TGFβ in the TME has been clearly
      demonstrated with the activation of CAFs being an important mechanism underlying immune cell
      exclusion. Exclusion of immune cells from tumors and local immunosuppression can both be
      reversed by AVID200 therapy.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Evaluation of the safety, tolerability, and dose-limiting toxicities (DLTs), to establish the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of sequential escalating doses of AVID200 when administered once every 3 weeks (Q3W) by IV infusion to patient cohorts (3)
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of Treatment-Emergent Adverse Events
time frame: From date of treatment until the date of first documented progression or date of death from any cause, whichever came first, for up to 24 months
description: Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
arm group label: Dose Level 1: 180 mg/m2 of AVID200
arm group type: Experimental
description: Intravenous infusion of AVID200 over 1 hour administered every three weeks. Starting dose for dose escalation.
arm group label: Dose Level 2: 550 mg/m2 of AVID200
arm group type: Experimental
description: Intravenous infusion of AVID200 over 1 hour administered every three weeks.
arm group label: Dose Level 3: 1100 mg/m2
arm group type: Experimental
description: Intravenous infusion of AVID200 over 1.5 hours administered every three weeks.
intervention type: Drug
intervention name: AVID200
description: A TGFβ receptor ectodomain-IgG Fc fusion protein inhibitor of TGFβ
arm group label: Dose Level 1: 180 mg/m2 of AVID200
arm group label: Dose Level 2: 550 mg/m2 of AVID200
arm group label: Dose Level 3: 1100 mg/m2
other name: TGFβ receptor ectodomain-IgG Fc fusion protein
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Paul I Nadler, MD
role: Study Director
affiliation: Forbius (Formation Biologics)
facility: 
facility: 
facility: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Neoplasms
sharing ipd: No