<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/NCT03272334</url>
  </required_header>
  <id_info>
    <org_study_id>19406</org_study_id>
    <nct_id>NCT03272334</nct_id>
  </id_info>
  <brief_title>Her2-BATS and Pembrolizumab in Metastatic Breast Cancer</brief_title>
  <acronym>Breast-47</acronym>
  <official_title>A Phase I/II Study of Anti-CD3 x Anti-HER2/Neu (Her2Bi) Armed Activated T Cells (ATC) and Pembrolizumab Combination Therapy in Women With Metastatic Breast Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Virginia</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>
      This proposal uses HER2Bi armed activated T-cells (HER2 BATs) to target breast cancer in&#xD;
      combination with pembrolizumab (PBZ) in women with metastatic breast cancer (MBC). Phase I&#xD;
      will determine a safe dose of the combination of PBZ and HER2 BATs in 3 to 18 patients. In&#xD;
      the phase II portion, an additional 12 patients will be treated at the selected dose to&#xD;
      further evaluate the safety and preliminary efficacy.&#xD;
&#xD;
      Study treatment includes a combination of 8 infusions of BATs using a previously established&#xD;
      schedule and one to three infusions of PBZ (200 mg per dose). PBZ will be added to 8&#xD;
      infusions of BATs in 3 schedules: #1) after the 8th BATs infusion; #2) after the 4th and 8th&#xD;
      BATs infusions; and then, #3) before the 1st and after the 4th and 8th BATs infusions.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Once subjects are determined eligible, white blood cells (lymphocytes) are collected via&#xD;
      leukapheresis procedure. Depending on arm/schedule, about 4-5 weeks later, study treatment&#xD;
      will begin. For HER2 BATs, the white blood cells, specifically T cells, are then mixed with&#xD;
      two proteins - OKT3 and IL-2 -- which activates the cells to multiply. After approximately 14&#xD;
      days in culture, the activated T cells are coated with OKT3 and trastuzumab/Herceptin&#xD;
      (HER2Bi), and washed to remove excess Herceptin in order to produce bispecific antibody armed&#xD;
      T cells (BATs). Cells are then frozen and stored until scheduled to be infused.&#xD;
&#xD;
      Follow-up appointment schedule will include clinic visits 2 weeks, 1 month, 3 months, and 6&#xD;
      months after the last dose of Pembrolizumab.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">December 29, 2017</start_date>
  <completion_date type="Anticipated">January 30, 2030</completion_date>
  <primary_completion_date type="Anticipated">January 30, 2024</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Pembrolizumab administered in combination with HER2 Bispecific Antibody Armed Activated T-Cell (BATs) infusions</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Dose Limiting Toxicities on each schedule/arm</measure>
    <time_frame>The study will not advance to the next schedule until 3 weeks after the last patient in the cohort completes her last dose of Pembrolizumab.</time_frame>
    <description>Maximum tolerated dose will be based on number of dose limiting toxicities in each schedule/arm</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Dose Limiting Toxicities on the selected arm in the expansion cohort</measure>
    <time_frame>All dose limiting toxicities are expected to be identified within the three weeks following the last dose of Pembrolizumab</time_frame>
    <description>Dose Limiting toxicities on the arm selected based on the dose/schedule selection part of the study. More patients will be enrolled onto this cohort to confirm safety.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immune response to treatment in blood</measure>
    <time_frame>Blood will be collected about 5 weeks before any treatment, just before first HER2 BATs infusion, before HER2 BATs #5, before HER2 BATs #8, and 2 weeks, 1 month, 3 months, and 6 months after last Pembrolizumab</time_frame>
    <description>Sequential monitoring of phenotype, IFN-γ EliSpots, anti-breast cancer cytotoxicity of peripheral blood mononuclear cells (PBMC) directed at breast cancer cell lines, Th1/Th2 serum cytokine patterns, and anti-breast cancer antibodies in the serum during the &quot;vaccinate and consolidate&quot; process</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Disease control rate</measure>
    <time_frame>Imaging will be done prior to study treatment, 1 month, 3 months and 6 months after completion of study treatment. Imaging will then be performed according to standard of care.</time_frame>
    <description>The percentage of subjects who achieve complete response, partial response and stable disease following treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Objective response rate</measure>
    <time_frame>Imaging will be done prior to study treatment, 1 month, 3 months and 6 months after completion of study treatment. Imaging will then be performed according to standard of care.</time_frame>
    <description>The percentage of subjects with a response of complete response (CR) or partial response (PR) per immune related response criteria (irRC)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response</measure>
    <time_frame>Imaging will be done prior to study treatment, 1 month, 3 months and 6 months after completion of study treatment. Imaging will then be performed according to standard of care.</time_frame>
    <description>The time from documentation of tumor response to disease progression.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Survival</measure>
    <time_frame>Every 3 months following last study visit until death or for 10 years</time_frame>
    <description>Progression-free and Overall Survival in a dose-expansion cohort of an additional 12 subjects</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">33</enrollment>
  <condition>Metastatic Breast Cancer</condition>
  <arm_group>
    <arm_group_label>Schedule #1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 1 infusion of Pembrolizumab in week #7. No interventions within weeks #3 and 4.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Schedule #2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 2 infusions of Pembrolizumab; the first given within weeks #3 - 4 and the second in week #7.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Schedule #3</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 3 infusions of pembrolizumab; the first given one week prior to first BATs infusion, the second is given within weeks #3 - 4, and the third at week #7.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>HER2 BATs with Pembrolizumab</intervention_name>
    <description>8 infusions of HER2 BATs with 1-3 infusions of Pembrolizumab</description>
    <arm_group_label>Schedule #1</arm_group_label>
    <arm_group_label>Schedule #2</arm_group_label>
    <arm_group_label>Schedule #3</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically confirmed breast cancer (infiltrating ductal or lobular breast&#xD;
             carcinoma) with evidence of measurable metastatic disease. Metastatic disease must be&#xD;
             biopsy proven.&#xD;
&#xD;
             a. Since histologic type, lymphatic permeation, blood vessel invasion, and degree of&#xD;
             anaplasia may be prognostic variables, appropriate slides of the primary lesion will&#xD;
             be requested for future review. HER2, estrogen, and progesterone receptor positivity&#xD;
             will be recorded.&#xD;
&#xD;
          2. Measurable lesion. Patients are required to have at least one measurable non-bone&#xD;
             lesion ≥10 mm that has not been irradiated.&#xD;
&#xD;
             a. Measurable metastatic disease documented by radiograph, CT scan, PET/CT, MRI, or&#xD;
             physical exam is required. Each subject will be required to have at least one&#xD;
             measurable lesion that has not been irradiated with a minimum size in at least one&#xD;
             diameter of ≥ 10 mm for liver lesions, lung, skin, and ≥ 15 mm lymph node metastases.&#xD;
             Biopsy of recurrent site(s) is not required.&#xD;
&#xD;
          3. Patients must have HER2 status determined by FISH or IHC. HER2 status of positive or&#xD;
             negative are both eligible for the study.&#xD;
&#xD;
             In order to be eligible for participation in this trial, the patient must also:&#xD;
&#xD;
          4. Be female ≥ 18 years of age&#xD;
&#xD;
          5. Be willing and able to provide written informed consent for the trial.&#xD;
&#xD;
          6. Have a performance status (PS) ECOG 0-1&#xD;
&#xD;
          7. Have a life expectancy ≥ 3 months&#xD;
&#xD;
          8. Be eligible for apheresis, as determined by the Stem Cell Transplant team&#xD;
&#xD;
          9. Demonstrate adequate organ function as defined below, all screening labs should be&#xD;
             performed within 10 days prior to apheresis.&#xD;
&#xD;
             Absolute lymphocyte count ≥ 500/mm3 Absolute neutrophil count (ANC) ≥1,500 /mcL&#xD;
             Platelets ≥ 100,000 / mcL Hemoglobin ≥ 9 g/dL (or ≥5.6 mmol/L without transfusion or&#xD;
             EPO dependency (within 7 days of assessment) BUN ≤ 1.5 X upper limit of normal (ULN)&#xD;
             Serum creatinine OR ≤1.5 X upper limit of normal (ULN) OR Measured or calculated&#xD;
             creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≥60 mL/min&#xD;
             for subject with creatinine levels &gt; 1.5 X institutional ULN Serum total bilirubin ≤&#xD;
             1.5 X ULN OR AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with&#xD;
             liver metastases Albumin &gt;2.5 mg/dL International Normalized Ratio (INR) or&#xD;
             Prothrombin Time (PT) ≤1.5 X ULN unless subject is receiving anticoagulant therapy&#xD;
             Activated Partial Thromboplastin Time (aPTT) as long as PT or PTT is within&#xD;
             therapeutic range of intended use of anticoagulants&#xD;
&#xD;
         10. Female patients of childbearing potential should have a negative urine or serum&#xD;
             pregnancy test at screening. If the urine test is positive or cannot be confirmed as&#xD;
             negative, a serum pregnancy test will be required.&#xD;
&#xD;
         11. Female patients of childbearing potential must be willing to use an adequate method of&#xD;
             contraception as outlined in Section 4.5.2, for the course of the study through 120&#xD;
             days after the last dose of study medication.&#xD;
&#xD;
         12. Patients must have had two or more lines of prior therapy (chemo or hormonal) in the&#xD;
             metastatic setting&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The patient must be excluded from participating in the trial if the subject:&#xD;
&#xD;
          1. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any&#xD;
             other form of immunosuppressive therapy within 7 days prior to leukapheresis.&#xD;
&#xD;
          2. Has a known history of active TB (Bacillus Tuberculosis)&#xD;
&#xD;
          3. Hypersensitivity to PBZ or any of its excipients.&#xD;
&#xD;
          4. Lack of recovery (i.e., ≤ Grade 1 or baseline prior to last line of cancer therapy)&#xD;
             from non-laboratory adverse events except ≤ Grade 2 neuropathy&#xD;
&#xD;
          5. Has history of another malignancy within the past 5 years. Exceptions include basal&#xD;
             cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone&#xD;
             potentially curative therapy or in situ cervical cancer.&#xD;
&#xD;
          6. Has known active central nervous system (CNS) metastases and/or carcinomatous&#xD;
             meningitis. Subjects with previously treated brain metastases may participate provided&#xD;
             they are stable (without evidence of progression by imaging for at least four weeks&#xD;
             prior to the first dose of trial treatment and any neurologic symptoms have returned&#xD;
             to baseline), have no evidence of new or enlarging brain metastases, and are not using&#xD;
             steroids for at least 7 days prior to leukapheresis. This exception does not include&#xD;
             carcinomatous meningitis which is excluded regardless of clinical stability.&#xD;
&#xD;
          7. Has active autoimmune disease that has required systemic treatment in the past 2 years&#xD;
             (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive&#xD;
             drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid&#xD;
             replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a&#xD;
             form of systemic treatment.&#xD;
&#xD;
          8. Has known history of, or any evidence of active, non-infectious pneumonitis.&#xD;
&#xD;
          9. Has an active infection requiring systemic therapy.&#xD;
&#xD;
         10. Has a history or current evidence of any condition, therapy, or laboratory abnormality&#xD;
             that might confound the results of the trial, interfere with the subject's&#xD;
             participation for the full duration of the trial, or is not in the best interest of&#xD;
             the subject to participate, in the opinion of the treating investigator.&#xD;
&#xD;
         11. Is pregnant or breastfeeding, or expecting to conceive children within the projected&#xD;
             duration of the trial, starting with the pre-screening or screening visit through 120&#xD;
             days after the last dose of trial treatment.&#xD;
&#xD;
         12. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.&#xD;
&#xD;
         13. Has Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies) or known history of&#xD;
             Hepatitis B (e.g., HBsAg reactive) or Hepatitis C antibody is detected. Note: Patients&#xD;
             may be eligible if HCV antibody is detected as long as HCV viral load is undetectable&#xD;
             following an FDA approved treatment regimen&#xD;
&#xD;
         14. Has received a live vaccine within 30 days of apheresis. Note: Seasonal influenza&#xD;
             vaccines for injection are generally inactivated flu vaccines and are allowed; however&#xD;
             intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are&#xD;
             not allowed.&#xD;
&#xD;
         15. Has a history of significant cardiac disease, including:&#xD;
&#xD;
               -  History of a recent myocardial infarction (within one year), a past myocardial&#xD;
                  infarction (more than one year ago) along with current coronary symptoms&#xD;
                  requiring medications and/or evidence of depressed left ventricular function&#xD;
                  (LVEF &lt; 45% by MUGA or ECHO).&#xD;
&#xD;
               -  Current history of angina/coronary symptoms requiring medications and/or evidence&#xD;
                  of depressed left ventricular function (LVEF &lt; 45% by MUGA or ECHO)&#xD;
&#xD;
               -  Clinical evidence of congestive heart failure requiring medical management&#xD;
                  (irrespective of ECHO results).&#xD;
&#xD;
         16. Pt may be excluded if, in the opinion of the PI and investigator team, the pt is not&#xD;
             capable of being compliant.&#xD;
      </textblock>
    </criteria>
    <gender>Female</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Patrick Dillon, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Ashley Donihee</last_name>
    <phone>14342436377</phone>
    <email>ZWZ6JM@hscmail.mcc.virginia.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lawrence Lum, MD, DSc</last_name>
    <phone>434-243-1375</phone>
    <email>lgl4f@virginia.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Ashley Donihee</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ashley Donihee</last_name>
      <phone>434-243-6377</phone>
      <email>ZWZ6JM@hscmail.mcc.virginia.edu</email>
    </contact>
    <contact_backup>
      <last_name>Lawrence Lum, MD, DSc</last_name>
      <phone>434-243-1375</phone>
      <email>lgl4f@virginia.edu</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, Dizon DS, Kouttab N, Maizel A, Colaiace W, Liu Q, Rathore R. Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clin Cancer Res. 2015 May 15;21(10):2305-14. doi: 10.1158/1078-0432.CCR-14-2280. Epub 2015 Feb 16.</citation>
    <PMID>25688159</PMID>
  </reference>
  <reference>
    <citation>Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG. Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients. Prostate Cancer. 2015;2015:285193. doi: 10.1155/2015/285193. Epub 2015 Feb 23.</citation>
    <PMID>25802762</PMID>
  </reference>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 5, 2017</study_first_posted>
  <last_update_submitted>January 18, 2023</last_update_submitted>
  <last_update_submitted_qc>January 18, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Virginia</investigator_affiliation>
    <investigator_full_name>Patrick Dillon, MD</investigator_full_name>
    <investigator_title>Assistant Professor, Hematology and Oncology</investigator_title>
  </responsible_party>
  <keyword>Metastatic Breast Cancer</keyword>
  <keyword>Adoptive Cell Therapy</keyword>
  <keyword>Armed Activated T-cells</keyword>
  <keyword>Bispecific Antibodies</keyword>
  <keyword>Immunotherapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Breast 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>
  <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/NCT03272334
org study id: 19406
nct id: NCT03272334
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This proposal uses HER2Bi armed activated T-cells (HER2 BATs) to target breast cancer in
      combination with pembrolizumab (PBZ) in women with metastatic breast cancer (MBC). Phase I
      will determine a safe dose of the combination of PBZ and HER2 BATs in 3 to 18 patients. In
      the phase II portion, an additional 12 patients will be treated at the selected dose to
      further evaluate the safety and preliminary efficacy.

      Study treatment includes a combination of 8 infusions of BATs using a previously established
      schedule and one to three infusions of PBZ (200 mg per dose). PBZ will be added to 8
      infusions of BATs in 3 schedules: #1) after the 8th BATs infusion; #2) after the 4th and 8th
      BATs infusions; and then, #3) before the 1st and after the 4th and 8th BATs infusions.
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via
      leukapheresis procedure. Depending on arm/schedule, about 4-5 weeks later, study treatment
      will begin. For HER2 BATs, the white blood cells, specifically T cells, are then mixed with
      two proteins - OKT3 and IL-2 -- which activates the cells to multiply. After approximately 14
      days in culture, the activated T cells are coated with OKT3 and trastuzumab/Herceptin
      (HER2Bi), and washed to remove excess Herceptin in order to produce bispecific antibody armed
      T cells (BATs). Cells are then frozen and stored until scheduled to be infused.

      Follow-up appointment schedule will include clinic visits 2 weeks, 1 month, 3 months, and 6
      months after the last dose of Pembrolizumab.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Pembrolizumab administered in combination with HER2 Bispecific Antibody Armed Activated T-Cell (BATs) infusions
primary purpose: Treatment
masking: None (Open Label)
measure: Dose Limiting Toxicities on each schedule/arm
time frame: The study will not advance to the next schedule until 3 weeks after the last patient in the cohort completes her last dose of Pembrolizumab.
description: Maximum tolerated dose will be based on number of dose limiting toxicities in each schedule/arm
measure: Dose Limiting Toxicities on the selected arm in the expansion cohort
time frame: All dose limiting toxicities are expected to be identified within the three weeks following the last dose of Pembrolizumab
description: Dose Limiting toxicities on the arm selected based on the dose/schedule selection part of the study. More patients will be enrolled onto this cohort to confirm safety.
measure: Immune response to treatment in blood
time frame: Blood will be collected about 5 weeks before any treatment, just before first HER2 BATs infusion, before HER2 BATs #5, before HER2 BATs #8, and 2 weeks, 1 month, 3 months, and 6 months after last Pembrolizumab
description: Sequential monitoring of phenotype, IFN-γ EliSpots, anti-breast cancer cytotoxicity of peripheral blood mononuclear cells (PBMC) directed at breast cancer cell lines, Th1/Th2 serum cytokine patterns, and anti-breast cancer antibodies in the serum during the "vaccinate and consolidate" process
measure: Disease control rate
time frame: Imaging will be done prior to study treatment, 1 month, 3 months and 6 months after completion of study treatment. Imaging will then be performed according to standard of care.
description: The percentage of subjects who achieve complete response, partial response and stable disease following treatment.
measure: Objective response rate
time frame: Imaging will be done prior to study treatment, 1 month, 3 months and 6 months after completion of study treatment. Imaging will then be performed according to standard of care.
description: The percentage of subjects with a response of complete response (CR) or partial response (PR) per immune related response criteria (irRC)
measure: Duration of response
time frame: Imaging will be done prior to study treatment, 1 month, 3 months and 6 months after completion of study treatment. Imaging will then be performed according to standard of care.
description: The time from documentation of tumor response to disease progression.
measure: Survival
time frame: Every 3 months following last study visit until death or for 10 years
description: Progression-free and Overall Survival in a dose-expansion cohort of an additional 12 subjects
arm group label: Schedule #1
arm group type: Experimental
description: At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 1 infusion of Pembrolizumab in week #7. No interventions within weeks #3 and 4.
arm group label: Schedule #2
arm group type: Experimental
description: At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 2 infusions of Pembrolizumab; the first given within weeks #3 - 4 and the second in week #7.
arm group label: Schedule #3
arm group type: Experimental
description: At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 3 infusions of pembrolizumab; the first given one week prior to first BATs infusion, the second is given within weeks #3 - 4, and the third at week #7.
intervention type: Drug
intervention name: HER2 BATs with Pembrolizumab
description: 8 infusions of HER2 BATs with 1-3 infusions of Pembrolizumab
arm group label: Schedule #1
arm group label: Schedule #2
arm group label: Schedule #3
criteria: 
gender: Female
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Patrick Dillon, MD
role: Principal Investigator
affiliation: University of Virginia
last name: Ashley Donihee
phone: 14342436377
email: ZWZ6JM@hscmail.mcc.virginia.edu
last name: Lawrence Lum, MD, DSc
phone: 434-243-1375
email: lgl4f@virginia.edu
facility: 
status: Recruiting
contact: 
contact backup: 
country: United States
citation: Lum LG, Thakur A, Al-Kadhimi Z, Colvin GA, Cummings FJ, Legare RD, Dizon DS, Kouttab N, Maizel A, Colaiace W, Liu Q, Rathore R. Targeted T-cell Therapy in Stage IV Breast Cancer: A Phase I Clinical Trial. Clin Cancer Res. 2015 May 15;21(10):2305-14. doi: 10.1158/1078-0432.CCR-14-2280. Epub 2015 Feb 16.
PMID: 25688159
citation: Vaishampayan U, Thakur A, Rathore R, Kouttab N, Lum LG. Phase I Study of Anti-CD3 x Anti-Her2 Bispecific Antibody in Metastatic Castrate Resistant Prostate Cancer Patients. Prostate Cancer. 2015;2015:285193. doi: 10.1155/2015/285193. Epub 2015 Feb 23.
PMID: 25802762
responsible party type: Principal Investigator
investigator affiliation: University of Virginia
investigator full name: Patrick Dillon, MD
investigator title: Assistant Professor, Hematology and Oncology
mesh term: Breast Neoplasms
mesh term: Pembrolizumab
sharing ipd: No