<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/NCT04420754</url>
  </required_header>
  <id_info>
    <org_study_id>19-12021154</org_study_id>
    <nct_id>NCT04420754</nct_id>
  </id_info>
  <brief_title>Study of AIC100 CAR T Cells in Relapsed/Refractory Thyroid Cancer</brief_title>
  <official_title>A Multicenter Phase I Study of AIC100 CAR T Cells in Relapsed and/or Refractory Advanced Thyroid Cancer or Anaplastic Thyroid Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>AffyImmune Therapeutics, Inc.</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>AffyImmune Therapeutics, Inc.</source>
  <oversight_info>
    <has_dmc>Yes</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>
      The purpose of this study is to assess the safety and tolerability and determine the&#xD;
      recommended Phase 2 dose of AIC100 Chimeric Antigen Receptor (CAR) T cells in patients with&#xD;
      relapsed/refractory poorly differentiated thyroid cancer and anaplastic thyroid cancer,&#xD;
      including newly diagnosed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary objective of this study is to assess the safety and tolerability of AIC100 CAR T&#xD;
      Cells and determine the recommended Phase 2 dose of AIC100 in patients with&#xD;
      relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic&#xD;
      thyroid cancer that are BRAF wild-type, including newly diagnosed, or BRAF mutant anaplastic&#xD;
      thyroid cancer after failure of BRAF mutant specific therapy.&#xD;
&#xD;
      Upon enrollment, patients will undergo apheresis for collection of autologous lymphocytes.&#xD;
      The autologous T cells will be transfected and expanded in vitro to generate the AIC100 CAR T&#xD;
      Cell product. After lymphodepleting chemotherapy, AIC100 CAR T Cells will be infused.&#xD;
&#xD;
      The study drug product, AIC100, consists of autologous CAR T cells targeting intercellular&#xD;
      adhesion molecule-1 (ICAM-1) on thyroid cancer. In addition, AIC100 cells express the&#xD;
      somatostatin receptor subtype 2 (SSTR2), which should enable imaging of AIC100 CAR T Cells.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 28, 2020</start_date>
  <completion_date type="Anticipated">December 2024</completion_date>
  <primary_completion_date type="Anticipated">September 28, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of overall Grade &gt;=3 Adverse Events (AE) and Serious Adverse Events (SAE)</measure>
    <time_frame>Up to 15 years post-infusion</time_frame>
    <description>The number of Grade 3, 4 and 5 AEs and SAEs that occur throughout the study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Incidence of anticipated AIC100 CAR T Cell related AEs, SAEs and adverse events of special interest (AESI)</measure>
    <time_frame>Up to 15 years post-infusion</time_frame>
    <description>The number of CAR T related adverse events that occur throughout the study, including AESIs, infusion-related reactions, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), tumor lysis syndrome (TLS) and new malignancies.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Determine recommended phase 2 dose</measure>
    <time_frame>Up to 15 years post-infusion</time_frame>
    <description>The recommended phase 2 dose will be determined through the dose escalation process</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Assessment of presence and frequency of AIC100 CAR T cells in peripheral blood and tumor samples (when available)</measure>
    <time_frame>Up to 15 years post-infusion</time_frame>
    <description>Patients will be monitored for expansion and persistence of AIC100 CAR transgenes after infusion by vector copy number (VCN) analysis</description>
  </secondary_outcome>
  <number_of_arms>6</number_of_arms>
  <enrollment type="Anticipated">30</enrollment>
  <condition>Anaplastic Thyroid Cancer</condition>
  <condition>Relapsed/Refractory Poorly Differentiated Thyroid Cancer</condition>
  <arm_group>
    <arm_group_label>Cohort -1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIC100 CAR T Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIC100 CAR T Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIC100 CAR T Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIC100 CAR T Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR T cells</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 2.5</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIC100 CAR T Cell Dose Level 2.5 (Flat Dose): 2.5 x 10e8 CAR T cells. The interim step-down dose of Cohort 2.5 may be evaluated, if needed, based on ongoing safety and efficacy data.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Cohort 4</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>AIC100 CAR T Cell Dose Level 4 (Flat Dose): 7.5 x 10e8 CAR T cells. The proposed escalation dose of Cohort 4 may be evaluated, if needed, based on ongoing safety and efficacy data.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>AIC100 CAR T Cells</intervention_name>
    <description>Autologous CAR T cells directed against ICAM-1</description>
    <arm_group_label>Cohort -1</arm_group_label>
    <arm_group_label>Cohort 1</arm_group_label>
    <arm_group_label>Cohort 2</arm_group_label>
    <arm_group_label>Cohort 2.5</arm_group_label>
    <arm_group_label>Cohort 3</arm_group_label>
    <arm_group_label>Cohort 4</arm_group_label>
    <other_name>AIC100</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Willing and able to participate in the study and provide written informed consent&#xD;
&#xD;
          2. Be ≥ 18 years of age on the day of signing the Informed Consent Form&#xD;
&#xD;
          3. Patients must have thyroid cancer that expresses ICAM-1 and that meets one of the&#xD;
             following diagnoses:&#xD;
&#xD;
               1. Anaplastic Thyroid Cancer BRAF wild-type at any stage, including newly diagnosed&#xD;
&#xD;
               2. Anaplastic Thyroid Cancer BRAF mutant after failure of or inability to tolerate&#xD;
                  BRAF- specific therapy&#xD;
&#xD;
               3. Poorly Differentiated Thyroid Cancer that has failed any of the following&#xD;
                  treatments: surgery radioactive iodine, chemotherapy, radiation therapy, and/or&#xD;
                  targeted therapies&#xD;
&#xD;
          4. Measurable disease by Computed Tomography (CT) or Positron Emission Tomography (PET)&#xD;
             PET/CT per RECIST v1.1&#xD;
&#xD;
             a. For ATC patients who do not have measurable disease at Screening, they are required&#xD;
             to have measurable disease at Baseline Day -7 to proceed in the study.&#xD;
&#xD;
          5. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2&#xD;
&#xD;
          6. Life expectancy greater than 8 weeks&#xD;
&#xD;
          7. Overall adequate hepatic, renal, bone marrow, cardiac, and coagulation function,&#xD;
             defined as the following:&#xD;
&#xD;
               1. Estimated creatinine clearance ≥ 50 mL/minute&#xD;
&#xD;
               2. Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST): normal or&#xD;
                  Grade 1. Note: Lymphodepleting Chemotherapy (LDC) agents can cause fluctuations&#xD;
                  in hepatic enzymes.&#xD;
&#xD;
               3. Serum total bilirubin: normal or Grade 1. Note: LDC agents can cause fluctuations&#xD;
                  in hepatic enzymes.&#xD;
&#xD;
               4. Serum albumin: normal or Grade 1. (human albumin supplementation is not allowed&#xD;
                  within 2 weeks prior to Screening assessment)&#xD;
&#xD;
               5. Hemodynamically stable and left ventricular ejection fraction ≥ 45%&#xD;
&#xD;
               6. Hematological parameters&#xD;
&#xD;
             i. Absolute neutrophil count &gt; 1000/μL without myeloid growth factor support for ≥ 2&#xD;
             weeks&#xD;
&#xD;
             ii. Absolute lymphocyte count ≥ 100/μL at screening and at apheresis&#xD;
&#xD;
             iii. Platelet count ≥ 50 × 1000/μL without platelet transfusion for ≥ 2 weeks&#xD;
&#xD;
             iv. Hemoglobin concentration &gt; 8 g/dL without red blood cell transfusion for ≥ 2 weeks&#xD;
&#xD;
          8. Has met the minimum washout time for previous cancer treatments before undergoing&#xD;
             apheresis or LDC, and in the Investigator's judgement, the patient is able to safely&#xD;
             undergo the procedure&#xD;
&#xD;
          9. (incorporated into inclusion criterion #7)&#xD;
&#xD;
         10. Females of reproductive potential (defined as all females physiologically capable of&#xD;
             becoming pregnant) must agree to use 1 highly effective method of contraception and 1&#xD;
             additional effective method from at least 28 days before enrollment/apheresis and for&#xD;
             at least 1 year after the infusion of AIC100 CAR T Cells.&#xD;
&#xD;
         11. Females of reproductive potential must have a negative serum beta-human chorionic&#xD;
             gonadotropin pregnancy test result at Screening&#xD;
&#xD;
         12. (incorporated into inclusion criterion #3)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Women who are pregnant or breastfeeding&#xD;
&#xD;
          2. Clinically significant, active, uncontrolled, systemic infection; the following are&#xD;
             not exclusionary:&#xD;
&#xD;
               1. Patients with HIV must have been on effective antiretroviral therapy for ≥ 4&#xD;
                  weeks prior to enrollment; must have an HIV viral load &lt; 400 copies/µL; no&#xD;
                  acquired immunodeficiency syndrome related opportunistic infections in the&#xD;
                  previous 12 months; and a CD4+ cell count ≥ 350 cells/µL&#xD;
&#xD;
               2. Patients with chronic hepatitis B virus (HBV) infection must be on antiviral&#xD;
                  therapy and have an HBV viral load below the limits of detection&#xD;
&#xD;
               3. Patients with chronic hepatitis C virus (HCV) infection must have completed&#xD;
                  therapy and have an HCV viral load below the limits of detection&#xD;
&#xD;
          3. Prior treatment with investigational gene therapy or CAR T cell therapy&#xD;
&#xD;
          4. Presence of active and clinically relevant central nervous system disorder such as&#xD;
             epilepsy, stroke, or symptomatic or uncontrolled brain metastases&#xD;
&#xD;
          5. Evidence of another malignancy within 2 years prior to Screening (except in-situ non&#xD;
             melanoma skin cancers, localized controlled prostate cancer, adequately treated Stage&#xD;
             1 uterine cancer that has a low risk of recurrence, or any other malignancies with&#xD;
             similar outcome)&#xD;
&#xD;
          6. (incorporated into exclusion criterion #2)&#xD;
&#xD;
          7. Active autoimmune disease (including but not limited to systemic lupus erythematosus,&#xD;
             Sjögren's Syndrome, rheumatoid arthritis (RA), psoriasis, multiple sclerosis,&#xD;
             inflammatory bowel disease) requiring immunosuppressive therapy within 4 weeks prior&#xD;
             to eligibility confirmation&#xD;
&#xD;
          8. Patients with severe chronic diseases of the kidney, liver, heart, lung; or any other&#xD;
             serious illness that, in the opinion of the Investigator, may affect the patient's&#xD;
             treatment, follow up, or assessments, including but not limited to uncontrolled&#xD;
             clinically significant neurological or psychiatric disorders or metabolic diseases&#xD;
&#xD;
          9. Patients who need long-term use of systemic corticosteroids &gt; 10 mg/day prednisone or&#xD;
             equivalent&#xD;
&#xD;
         10. Allergy to any of the chemotherapy drugs given during lymphodepletion or known&#xD;
             hypersensitivity to any component of AIC100 CAR T Cells, including excipients&#xD;
&#xD;
         11. Receipt of a COVID-19 vaccine within 4 weeks before Screening&#xD;
&#xD;
         12. Concurrent participation in another interventional clinical study during participation&#xD;
             in this study&#xD;
&#xD;
               1. Prior treatment with any gene therapy or genetically modified cell therapy,&#xD;
                  including CAR T cells&#xD;
&#xD;
               2. Prior treatment with ICAM-1 directed antibody, bispecific T cell engager, or&#xD;
                  antibody drug conjugate, unless there is confirmed ICAM-1 expression (by&#xD;
                  immunohistochemistry) after progression or relapse following most recent ICAM-1&#xD;
                  directed treatment.&#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>Sonal Gupta, MD PhD</last_name>
    <role>Study Director</role>
    <affiliation>AffyImmune Therapeutics, Inc.</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sonal Gupta, MD PhD</last_name>
    <phone>508-654-3600</phone>
    <phone_ext>3</phone_ext>
    <email>sgupta@affyimmune.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dawn Buchanan</last_name>
    <phone>508-654-3600</phone>
    <phone_ext>5</phone_ext>
    <email>dbuchanan@affyimmune.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>City of Hope National Medical Center, City of Hope Medical Center</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Victoria Villaflor, MD</last_name>
      <phone>800-826-4673</phone>
      <email>vvillaflor@coh.org</email>
    </contact>
    <investigator>
      <last_name>Victoria Villaflor, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Northwestern Memorial Hospital</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Lori Ackatz, RN</last_name>
      <phone>312-695-3101</phone>
      <email>cancer@northwestern.edu</email>
    </contact>
    <investigator>
      <last_name>Jochen Lorch, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </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>
    <status>Recruiting</status>
    <contact>
      <last_name>Shehanie Brana, RN</last_name>
      <phone>713-563-4406</phone>
      <email>SHBrana@mdanderson.org</email>
    </contact>
    <investigator>
      <last_name>Samer Srour, MB ChB</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Maria E Cabanillas, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Mark Zafereo, MD, FACS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 9, 2020</study_first_posted>
  <last_update_submitted>August 16, 2023</last_update_submitted>
  <last_update_submitted_qc>August 16, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>AIC100</keyword>
  <keyword>CAR T Cell</keyword>
  <keyword>Anaplastic Thyroid Cancer</keyword>
  <keyword>Poorly Differentiated Thyroid Cancer</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Thyroid Neoplasms</mesh_term>
    <mesh_term>Thyroid Carcinoma, Anaplastic</mesh_term>
    <mesh_term>Thyroid Diseases</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/NCT04420754
org study id: 19-12021154
nct id: NCT04420754
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this study is to assess the safety and tolerability and determine the
      recommended Phase 2 dose of AIC100 Chimeric Antigen Receptor (CAR) T cells in patients with
      relapsed/refractory poorly differentiated thyroid cancer and anaplastic thyroid cancer,
      including newly diagnosed.
The primary objective of this study is to assess the safety and tolerability of AIC100 CAR T
      Cells and determine the recommended Phase 2 dose of AIC100 in patients with
      relapsed/refractory poorly differentiated thyroid cancer and in patients with anaplastic
      thyroid cancer that are BRAF wild-type, including newly diagnosed, or BRAF mutant anaplastic
      thyroid cancer after failure of BRAF mutant specific therapy.

      Upon enrollment, patients will undergo apheresis for collection of autologous lymphocytes.
      The autologous T cells will be transfected and expanded in vitro to generate the AIC100 CAR T
      Cell product. After lymphodepleting chemotherapy, AIC100 CAR T Cells will be infused.

      The study drug product, AIC100, consists of autologous CAR T cells targeting intercellular
      adhesion molecule-1 (ICAM-1) on thyroid cancer. In addition, AIC100 cells express the
      somatostatin receptor subtype 2 (SSTR2), which should enable imaging of AIC100 CAR T Cells.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of overall Grade >=3 Adverse Events (AE) and Serious Adverse Events (SAE)
time frame: Up to 15 years post-infusion
description: The number of Grade 3, 4 and 5 AEs and SAEs that occur throughout the study.
measure: Incidence of anticipated AIC100 CAR T Cell related AEs, SAEs and adverse events of special interest (AESI)
time frame: Up to 15 years post-infusion
description: The number of CAR T related adverse events that occur throughout the study, including AESIs, infusion-related reactions, cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), tumor lysis syndrome (TLS) and new malignancies.
measure: Determine recommended phase 2 dose
time frame: Up to 15 years post-infusion
description: The recommended phase 2 dose will be determined through the dose escalation process
measure: Assessment of presence and frequency of AIC100 CAR T cells in peripheral blood and tumor samples (when available)
time frame: Up to 15 years post-infusion
description: Patients will be monitored for expansion and persistence of AIC100 CAR transgenes after infusion by vector copy number (VCN) analysis
arm group label: Cohort -1
arm group type: Experimental
description: AIC100 CAR T Cell Dose Level -1 (Flat Dose): 1 x 10e6 CAR T cells
arm group label: Cohort 1
arm group type: Experimental
description: AIC100 CAR T Cell Dose Level 1 (Flat Dose): 1 x 10e7 CAR T cells
arm group label: Cohort 2
arm group type: Experimental
description: AIC100 CAR T Cell Dose Level 2 (Flat Dose): 1 x 10e8 CAR T cells
arm group label: Cohort 3
arm group type: Experimental
description: AIC100 CAR T Cell Dose Level 3 (Flat Dose): 5 x 10e8 CAR T cells
arm group label: Cohort 2.5
arm group type: Experimental
description: AIC100 CAR T Cell Dose Level 2.5 (Flat Dose): 2.5 x 10e8 CAR T cells. The interim step-down dose of Cohort 2.5 may be evaluated, if needed, based on ongoing safety and efficacy data.
arm group label: Cohort 4
arm group type: Experimental
description: AIC100 CAR T Cell Dose Level 4 (Flat Dose): 7.5 x 10e8 CAR T cells. The proposed escalation dose of Cohort 4 may be evaluated, if needed, based on ongoing safety and efficacy data.
intervention type: Biological
intervention name: AIC100 CAR T Cells
description: Autologous CAR T cells directed against ICAM-1
arm group label: Cohort -1
arm group label: Cohort 1
arm group label: Cohort 2
arm group label: Cohort 2.5
arm group label: Cohort 3
arm group label: Cohort 4
other name: AIC100
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sonal Gupta, MD PhD
role: Study Director
affiliation: AffyImmune Therapeutics, Inc.
last name: Sonal Gupta, MD PhD
phone: 508-654-3600
phone ext: 3
email: sgupta@affyimmune.com
last name: Dawn Buchanan
phone: 508-654-3600
phone ext: 5
email: dbuchanan@affyimmune.com
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Thyroid Neoplasms
mesh term: Thyroid Carcinoma, Anaplastic
mesh term: Thyroid Diseases
sharing ipd: No