<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/NCT04408898</url>
  </required_header>
  <id_info>
    <org_study_id>ADP 0044-003</org_study_id>
    <nct_id>NCT04408898</nct_id>
  </id_info>
  <brief_title>SPEARHEAD 2 Study in Subjects With Recurrent or Metastatic Head and Neck Cancer</brief_title>
  <official_title>A Phase 2 Pilot Study of ADP-A2M4 in Combination With Pembrolizumab in Subjects With Recurrent or Metastatic Head and Neck Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Adaptimmune</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Adaptimmune</source>
  <oversight_info>
    <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 study to investigate the efficacy and safety of ADP-A2M4 in combination with&#xD;
      pembrolizumab in HLA-A*02 eligible and MAGE-A4 positive subjects with recurrent or metastatic&#xD;
      Head and Neck cancer.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Challenges with recruitment&#xD;
  </why_stopped>
  <start_date type="Actual">July 2, 2020</start_date>
  <completion_date type="Anticipated">December 2021</completion_date>
  <primary_completion_date type="Anticipated">December 2021</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Efficacy: Overall Response Rate (ORR)</measure>
    <time_frame>2.5 years</time_frame>
    <description>ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Best overall response (BOR)</measure>
    <time_frame>2.5 years</time_frame>
    <description>BOR defined as the best response recorded from the date of T cell infusion until disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to response (TTR)</measure>
    <time_frame>2.5 years</time_frame>
    <description>TTR defined as the duration between T cell infusion and the initial date of the confirmed response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR)</measure>
    <time_frame>2.5 years</time_frame>
    <description>DoR defined as the duration from the initial date of the confirmed response to the date of PD (or death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of stable disease (DoSD)</measure>
    <time_frame>2.5 years</time_frame>
    <description>DoSD defined as the duration from the date of T cell infusion to the date of PD (or death).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression- free survival (PFS)</measure>
    <time_frame>2.5 years</time_frame>
    <description>PFS defined as the interval between the date T cell infusion and the earliest date of disease progression based on RECIST v1.1 or death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS)</measure>
    <time_frame>2.5 years</time_frame>
    <description>OS defined the duration between T cell infusion and death due to any cause.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs)</measure>
    <time_frame>2.5 years</time_frame>
    <description>Determination of incidence, severity and duration of adverse events through assessment of adverse events including SAEs. Adverse events will be collected and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest</measure>
    <time_frame>2.5 years</time_frame>
    <description>Adverse events of special interest will be listed along with duration and toxicity grade.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells</measure>
    <time_frame>15 years</time_frame>
    <description>Evaluation of RCL using PCR-based assay in peripheral blood.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Head and Neck Cancer</condition>
  <arm_group>
    <arm_group_label>ADP-A2M4 T cells in combination with pembrolizumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Genetic</intervention_type>
    <intervention_name>ADP-A2M4 in combination with pembrolizumab.</intervention_name>
    <description>Single infusion of autologous genetically modified ADP-A2M4 Dose: 1.0 x109 to 10x109 transduced cells by a single intravenous infusion Repeat doses of pembrolizumab every 3 weeks. Dose: 200mg</description>
    <arm_group_label>ADP-A2M4 T cells in combination with pembrolizumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Key Inclusion Criteria&#xD;
&#xD;
          -  Age ≥18 and &lt;75 years&#xD;
&#xD;
          -  Diagnosis of head and neck squamous cell carcinoma with metastatic or unresectable,&#xD;
             recurrent disease. confirmed by histology cytology.&#xD;
&#xD;
          -  Checkpoint inhibitor naïve and indicated for pembrolizumab or currently receiving&#xD;
             pembrolizumab (monotherapy). May have received prior platinum containing chemotherapy&#xD;
             regimen or checkpoint inhibitor therapy.&#xD;
&#xD;
          -  Subjects that have already received pembrolizumab (alone or in combination) and are&#xD;
             progressing or have completed immune checkpoint inhibitor therapy for&#xD;
             recurrent/metastatic disease, may still be enrolled and will skip Part A of the study.&#xD;
&#xD;
        These subjects will enroll into Part B when manufactured T cells are available.&#xD;
&#xD;
          -  Measurable disease according to RECIST v1.1.&#xD;
&#xD;
          -  HLA-A*02 positive by central laboratory.&#xD;
&#xD;
          -  Tumor shows MAGE-A4 expression confirmed by central laboratory.&#xD;
&#xD;
          -  ECOG Performance Status of 0 or 1.&#xD;
&#xD;
          -  Left ventricular ejection fraction (LVEF) ≥50%.&#xD;
&#xD;
        Note: other protocol defined Inclusion criteria may apply&#xD;
&#xD;
        Key Exclusion Criteria:&#xD;
&#xD;
          -  Positive for any HLA-A*02 allele other than: one of the inclusion alleles, HLA-&#xD;
             A*02:07P or HLA-A*02 null alleles&#xD;
&#xD;
          -  History of allergic reactions attributed to compounds of similar chemical or biologic&#xD;
             composition to fludarabine, cyclophosphamide or other agents used in the study or&#xD;
             history of severe hypersensitivity to another monoclonal antibody.&#xD;
&#xD;
          -  History of autoimmune or immune mediated disease&#xD;
&#xD;
          -  Leptomeningeal disease, carcinomatous meningitis or CNS metastases.&#xD;
&#xD;
          -  Other prior malignancy that is not considered by the Investigator to be in complete&#xD;
             remission&#xD;
&#xD;
          -  Clinically significant cardiovascular disease&#xD;
&#xD;
          -  Uncontrolled intercurrent illness&#xD;
&#xD;
          -  Active infection with human immunodeficiency virus, hepatitis B virus, hepatitis C&#xD;
             virus, or human T cell leukemia virus&#xD;
&#xD;
          -  Pregnant or breastfeeding&#xD;
&#xD;
        Note: other protocol defined Exclusion criteria may apply.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Mayo Clinic Phoenix</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85054</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California San Diego</name>
      <address>
        <city>San Diego</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Kansas Medical Center</name>
      <address>
        <city>Kansas City</city>
        <state>Kansas</state>
        <zip>66160</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Karmanos Cancer Insitute</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Providence Cancer Institute Franz Head and Neck Clinic</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Vanderbilt-Ingram Cancer Center</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212</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>West Virginia University Cancer Institute</name>
      <address>
        <city>Morgantown</city>
        <state>West Virginia</state>
        <zip>26506</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>May 27, 2020</study_first_submitted>
  <study_first_submitted_qc>May 27, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">May 29, 2020</study_first_posted>
  <last_update_submitted>November 8, 2021</last_update_submitted>
  <last_update_submitted_qc>November 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 16, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Cell Therapy</keyword>
  <keyword>T-cell Therapy</keyword>
  <keyword>SPEAR T-Cell</keyword>
  <keyword>Head and Neck Cancer</keyword>
  <keyword>MAGE-A4</keyword>
  <keyword>ADP-A2M4</keyword>
  <keyword>Immuno-oncology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Head and Neck Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Pembrolizumab</mesh_term>
  </intervention_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/NCT04408898
org study id: ADP 0044-003
nct id: NCT04408898
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a study to investigate the efficacy and safety of ADP-A2M4 in combination with
      pembrolizumab in HLA-A*02 eligible and MAGE-A4 positive subjects with recurrent or metastatic
      Head and Neck cancer.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Efficacy: Overall Response Rate (ORR)
time frame: 2.5 years
description: ORR is defined as the proportion of complete responses or partial responses as assessed by RECIST v1.1
measure: Best overall response (BOR)
time frame: 2.5 years
description: BOR defined as the best response recorded from the date of T cell infusion until disease progression.
measure: Time to response (TTR)
time frame: 2.5 years
description: TTR defined as the duration between T cell infusion and the initial date of the confirmed response.
measure: Duration of response (DoR)
time frame: 2.5 years
description: DoR defined as the duration from the initial date of the confirmed response to the date of PD (or death).
measure: Duration of stable disease (DoSD)
time frame: 2.5 years
description: DoSD defined as the duration from the date of T cell infusion to the date of PD (or death).
measure: Progression- free survival (PFS)
time frame: 2.5 years
description: PFS defined as the interval between the date T cell infusion and the earliest date of disease progression based on RECIST v1.1 or death due to any cause.
measure: Overall survival (OS)
time frame: 2.5 years
description: OS defined the duration between T cell infusion and death due to any cause.
measure: To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining incidence of Adverse events (AEs) including serious adverse events (SAEs)
time frame: 2.5 years
description: Determination of incidence, severity and duration of adverse events through assessment of adverse events including SAEs. Adverse events will be collected and graded as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
measure: To evaluate the safety and tolerability of ADP-A2M4 with pembrolizumab by determining the incidence, severity and duration of the AEs of special interest
time frame: 2.5 years
description: Adverse events of special interest will be listed along with duration and toxicity grade.
measure: To evaluate safety of ADP-A2M4 with pembrolizumab through measurement of Replication-competent Lentivirus in genetically engineered T-cells
time frame: 15 years
description: Evaluation of RCL using PCR-based assay in peripheral blood.
arm group label: ADP-A2M4 T cells in combination with pembrolizumab
arm group type: Experimental
intervention type: Genetic
intervention name: ADP-A2M4 in combination with pembrolizumab.
description: Single infusion of autologous genetically modified ADP-A2M4 Dose: 1.0 x109 to 10x109 transduced cells by a single intravenous infusion Repeat doses of pembrolizumab every 3 weeks. Dose: 200mg
arm group label: ADP-A2M4 T cells in combination with pembrolizumab
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Head and Neck Neoplasms
mesh term: Pembrolizumab