xml: <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/NCT05989828</url>
    </required_header>
    <id_info>
      <org_study_id>1B-23-1</org_study_id>
      <secondary_id>NCI-2023-04697</secondary_id>
      <secondary_id>1B-23-1</secondary_id>
      <secondary_id>P30CA014089</secondary_id>
      <nct_id>NCT05989828</nct_id>
    </id_info>
    <brief_title>A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer</brief_title>
    <official_title>Phase Ib Clinical Trial of Autologous Anti-NY-ESO-1 TCR-Engineered T Cells in Patients With Relapsed/Refractory Locally Advanced or Metastatic NY-ESO-1-Expressing Triple Negative Breast Cancer</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Southern California</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Cancer Institute (NCI)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Southern California</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>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        This phase Ib trial tests the safety, side effects and best dose of anti-HLA-A2/NY-ESO-1&#xD;
        T-cell receptor (TCR)-transduced autologous T lymphocytes (A2-ESO-1 TCR-T cells) in treating&#xD;
        patients with NY-ESO-1 overexpression positive triple negative breast cancer (TNBC) that has&#xD;
        come back after a period of improvement (relapsed/recurrent) or that does not respond to&#xD;
        treatment (refractory), and that may have spread from where it first started (primary site)&#xD;
        to nearby tissue, lymph nodes (advanced) or to other places in the body (metastatic).&#xD;
        NY-ESO-1 is an antigen found on the surface of many different types of tumor cells including&#xD;
        TNBC. Antigens make it possible for immune cells to recognize and kill germ cells that invade&#xD;
        the body, however, it is more difficult for immune cells to recognize antigens on tumor&#xD;
        cells. T cells are a special type of immune cell in the blood. These T cells may be trained&#xD;
        to recognize the NY-ESO-1 antigen on tumor cells, allowing the T cells to attack and kill&#xD;
        those tumor cells. The A2-ESO-1 TCR-T cells are T cells that have been removed from the&#xD;
        patient's blood through a process called leukapheresis and then changed in the laboratory to&#xD;
        recognize NY-ESO-1 on tumor cells. When given back to the patient, these A2-ESO-1 TCR-T cells&#xD;
        find and attack tumor cells that express NY-ESO-1. Chemotherapy drugs, such as&#xD;
        cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells,&#xD;
        either by killing the cells, by stopping them from dividing, or by stopping them from&#xD;
        spreading. They are given before the T cells to support optimum activity of the A2-ESO-1&#xD;
        TCR-T cells. IL-2 (aldesleukin) is in a class of drugs known as cytokines. It is a man-made&#xD;
        version of a naturally occurring protein that stimulates the body to produce other chemicals&#xD;
        which increase the body's ability to fight cancer. A2-ESO-1 TCR-T cells may kill more tumor&#xD;
        cells in patients with recurrent or refractory advanced or metastatic TNBC that overexpresses&#xD;
        NY-ESO-1.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        PRIMARY OBJECTIVES:&#xD;
  &#xD;
        I. To determine the maximum tolerated dose (MTD) of anti-HLA-A2/NY-ESO-1 TCR-transduced&#xD;
        autologous T lymphocytes (A2-ESO-1 TCR-engineered T cells) in patients with&#xD;
        relapsed/refractory locally advanced or metastatic TNBC that overexpresses NY-ESO-1 by using&#xD;
        the Bayesian optimal interval (BOIN) design.&#xD;
  &#xD;
        II. To determine the dose-limiting toxicities (DLTs) of A2-ESO-1 TCR-engineered T cells in&#xD;
        patients with relapsed/refractory locally advanced or metastatic TNBC that overexpresses&#xD;
        NY-ESO-1, as assessed by the National Cancer Institute Common Terminology Criteria for&#xD;
        Adverse Events (NCI CTCAE) version (v)5.0.&#xD;
  &#xD;
        SECONDARY OBJECTIVES:&#xD;
  &#xD;
        I. To evaluate the antitumor activity of A2-ESO-1 TCR-engineered T cells, as assessed by the&#xD;
        Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.&#xD;
  &#xD;
        II. To evaluate the immunological activity (i.e., persistence, function) of A2-ESO-1&#xD;
        TCR-engineered T cells.&#xD;
  &#xD;
        EXPLORATORY OBJECTIVE:&#xD;
  &#xD;
        I. To evaluate the correlative markers of A2-ESO-1 TCR-engineered T cells, including but not&#xD;
        limited to PD-L1 expression and immune cell populations such as regulatory T cells (Tregs)&#xD;
        and tumor-associated macrophages (TAMs).&#xD;
  &#xD;
        OUTLINE: This is a dose-escalation study of A2-ESO-1 TCR-T cells.&#xD;
  &#xD;
        Patients undergo leukapheresis on day -28 then receive cyclophosphamide intravenously (IV)&#xD;
        over 1 hour on days -7 and -6 followed by fludarabine IV over 30 minutes on days -5 to -1.&#xD;
        Patients then receive A2-ESO-1 TCR-T cells IV over 30 minutes on day 0 followed by&#xD;
        aldesleukin IV over 15 minutes on days 0 to 2. Patients also undergo blood sample collection&#xD;
        and computed tomography (CT) scans throughout the study. Additionally, patients may undergo a&#xD;
        breast biopsy, a mammogram, breast magnetic resonance imaging (MRI), and breast ultrasound&#xD;
        (US) at screening and follow up, and echocardiography (ECHO) or multi-gated acquisition scan&#xD;
        (MUGA) at screening.&#xD;
  &#xD;
        After completion of study treatment, patients are followed up at 3, 6, and 12 months and then&#xD;
        yearly for up to 15 years or until disease progression, voluntary study withdrawal or study&#xD;
        discontinuation, whichever occurs first.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2, 2023</start_date>
    <completion_date type="Anticipated">April 2, 2026</completion_date>
    <primary_completion_date type="Anticipated">October 2, 2025</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>Single Group Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Maximum tolerated dose (MTD) of anti-HLA-A2/NY-ESO-1 T-cell receptor (TCR)-transduced autologous T lymphocytes (A2-ESO-1 TCR-engineered T cells)</measure>
      <time_frame>Up to 8 weeks after A2-ESO-1 TCR-engineered T cell infusion</time_frame>
      <description>Will employ the Bayesian optimal interval to find the MTD.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Incidence of dose-limiting toxicities</measure>
      <time_frame>Up to 8 weeks after A2 ESO-1 TCR-engineered T cell infusion</time_frame>
      <description>Defined as any treatment-related death or any greater than or equal to grade 3 adverse event (AE) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Antitumor activity</measure>
      <time_frame>At pre-treatment and 6 months post-treatment</time_frame>
      <description>Antitumor activity will be assessed by RECIST 1.1. Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) = at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum longest diameter as a reference, Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD) using the smallest sum longest diameter since treatment start as reference, PD = At least a ≥20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in PD-1 expression on T cells</measure>
      <time_frame>At pre-treatment and 6 months post-treatment</time_frame>
      <description>Levels of PD-1 expression on T cells will be monitored. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in NY-ESO-1-specific TCR-engineered T cells</measure>
      <time_frame>At pre-treatment and 6 months post-treatment</time_frame>
      <description>Levels of NY-ESO-1-specific TCR-engineered T cells will be monitored to determine whether these T cells are persistent. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change in regulatory T cells (Treg)</measure>
      <time_frame>At pre-treatment and 6 months post-treatment</time_frame>
      <description>Because NY-ESO-1-specific TCR-engineered CD4+ T cells may differentiate into Treg cells, levels of Treg cells will be monitored. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">20</enrollment>
    <condition>Triple Negative Breast Cancer</condition>
    <arm_group>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Patients undergo leukapheresis on day -28 then receive cyclophosphamide IV over 1 hour on days -7 and -6 followed by fludarabine IV over 30 minutes on days -5 to -1. Patients then receive A2-ESO-1 TCR-T cells IV over 30 minutes on day 0 followed by aldesleukin IV over 15 minutes on days 0 to 2. Patients also undergo blood sample collection and CT scans throughout the study. Additionally, patients may undergo a breast biopsy, a mammogram, breast MRI, and breast US at screening and follow up, and ECHO or MUGA at screening.</description>
    </arm_group>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Aldesleukin</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>125-L-Serine-2-133-interleukin 2</other_name>
      <other_name>Proleukin</other_name>
      <other_name>r-serHuIL-2</other_name>
      <other_name>Recombinant Human IL-2</other_name>
      <other_name>Recombinant Human Interleukin-2</other_name>
    </intervention>
    <intervention>
      <intervention_type>Biological</intervention_type>
      <intervention_name>Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>Anti-HLA-A2/NY-ESO1 TCR-transduced Autologous T cells</other_name>
      <other_name>Autologous Anti-HLA-A2/NY-ESO1 TCR-transduced T Lymphocytes</other_name>
      <other_name>Autologous HLA-A2/NY-ESO-1-specific TCR Gene-transduced T-lymphocytes</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biopsy</intervention_name>
      <description>Undergo biopsy of breast tumor</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>BIOPSY_TYPE</other_name>
      <other_name>Bx</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Biospecimen Collection</intervention_name>
      <description>Undergo blood sample collection</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>Biological Sample Collection</other_name>
      <other_name>Biospecimen Collected</other_name>
      <other_name>Specimen Collection</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Computed Tomography</intervention_name>
      <description>Undergo CT scan</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>CAT</other_name>
      <other_name>CAT Scan</other_name>
      <other_name>Computed Axial Tomography</other_name>
      <other_name>Computerized Axial Tomography</other_name>
      <other_name>Computerized axial tomography (procedure)</other_name>
      <other_name>Computerized Tomography</other_name>
      <other_name>CT</other_name>
      <other_name>CT Scan</other_name>
      <other_name>tomography</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Cyclophosphamide</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>(-)-Cyclophosphamide</other_name>
      <other_name>2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate</other_name>
      <other_name>Carloxan</other_name>
      <other_name>Ciclofosfamida</other_name>
      <other_name>Ciclofosfamide</other_name>
      <other_name>Cicloxal</other_name>
      <other_name>Clafen</other_name>
      <other_name>Claphene</other_name>
      <other_name>CP monohydrate</other_name>
      <other_name>CTX</other_name>
      <other_name>CYCLO-cell</other_name>
      <other_name>Cycloblastin</other_name>
      <other_name>Cycloblastine</other_name>
      <other_name>Cyclophospham</other_name>
      <other_name>Cyclophosphamid monohydrate</other_name>
      <other_name>Cyclophosphamide Monohydrate</other_name>
      <other_name>Cyclophosphamidum</other_name>
      <other_name>Cyclophosphan</other_name>
      <other_name>Cyclophosphane</other_name>
      <other_name>Cyclophosphanum</other_name>
      <other_name>Cyclostin</other_name>
      <other_name>Cyclostine</other_name>
      <other_name>Cytophosphan</other_name>
      <other_name>Cytophosphane</other_name>
      <other_name>Cytoxan</other_name>
      <other_name>Fosfaseron</other_name>
      <other_name>Genoxal</other_name>
      <other_name>Genuxal</other_name>
      <other_name>Ledoxina</other_name>
      <other_name>Mitoxan</other_name>
      <other_name>Neosar</other_name>
      <other_name>Revimmune</other_name>
      <other_name>Syklofosfamid</other_name>
      <other_name>WR- 138719</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Echocardiography</intervention_name>
      <description>Undergo ECHO</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>EC</other_name>
    </intervention>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Fludarabine</intervention_name>
      <description>Given IV</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>Fluradosa</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Leukapheresis</intervention_name>
      <description>Undergo leukapheresis</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>Leukocytopheresis</other_name>
      <other_name>Therapeutic Leukopheresis</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Magnetic Resonance Imaging</intervention_name>
      <description>Undergo breast MRI</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>Magnetic Resonance</other_name>
      <other_name>Magnetic resonance imaging (procedure)</other_name>
      <other_name>Magnetic Resonance Imaging Scan</other_name>
      <other_name>Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance</other_name>
      <other_name>MR</other_name>
      <other_name>MR Imaging</other_name>
      <other_name>MRI</other_name>
      <other_name>MRI Scan</other_name>
      <other_name>NMR Imaging</other_name>
      <other_name>NMRI</other_name>
      <other_name>Nuclear Magnetic Resonance Imaging</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Mammogram</intervention_name>
      <description>Undergo mammogram</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Multigated Acquisition Scan</intervention_name>
      <description>Undergo MUGA scan</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>Blood Pool Scan</other_name>
      <other_name>Equilibrium Radionuclide Angiography</other_name>
      <other_name>Gated Blood Pool Imaging</other_name>
      <other_name>Gated Heart Pool Scan</other_name>
      <other_name>MUGA</other_name>
      <other_name>MUGA Scan</other_name>
      <other_name>Multi-Gated Acquisition Scan</other_name>
      <other_name>Radionuclide Ventriculogram Scan</other_name>
      <other_name>Radionuclide Ventriculography</other_name>
      <other_name>RNVG</other_name>
      <other_name>SYMA Scanning</other_name>
      <other_name>Synchronized Multigated Acquisition Scanning</other_name>
    </intervention>
    <intervention>
      <intervention_type>Procedure</intervention_type>
      <intervention_name>Ultrasound Imaging</intervention_name>
      <description>Undergo ultrasound of breast</description>
      <arm_group_label>Treatment (A2-ESO-1 TCR-T cells)</arm_group_label>
      <other_name>2-Dimensional Grayscale Ultrasound Imaging</other_name>
      <other_name>2-Dimensional Ultrasound Imaging</other_name>
      <other_name>2D-US</other_name>
      <other_name>Ultrasonography</other_name>
      <other_name>Ultrasound</other_name>
      <other_name>Ultrasound Test</other_name>
      <other_name>Ultrasound, Medical</other_name>
      <other_name>US</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Female aged &gt;= 18 years&#xD;
  &#xD;
            -  Histologically confirmed advanced or metastatic TNBC that have relapsed on or are&#xD;
               refractory to 2 or more lines of standard-of-care therapy including immune checkpoint&#xD;
               inhibitors, chemotherapy, trastuzumab deruxtecan (TDX-d) and poly-ADP ribose&#xD;
               polymerase (PARP) inhibitors if indicated, but less than 4 lines of total therapies.&#xD;
               TNBC is defined as estrogen receptor (ER) and progesterone receptor negative (&lt; 10%&#xD;
               immunohistochemistry [IHC] staining) and HER2 negative (IHC 1+ or 0 AND/OR in situ&#xD;
               hybridization negative based on:&#xD;
  &#xD;
                 -  Single-probe average HER2 copy number &lt; 4.0 signals/cell&#xD;
  &#xD;
                 -  Dual-probe HER2/CEP17 ratio &lt; 2.0 with an average HER2 copy number &lt; 4.0&#xD;
                    signals/cell)&#xD;
  &#xD;
            -  HLA-A2+ and tumoral overexpression of NY-ESO-1 (2 to 3+ IHC staining in &gt; 50% of&#xD;
               cells)&#xD;
  &#xD;
            -  Have measurable disease based on RECIST 1.1&#xD;
  &#xD;
            -  Life expectancy &gt;= 6 months&#xD;
  &#xD;
            -  Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1&#xD;
  &#xD;
            -  Hemoglobin &gt;= 9.0 g/dL (transfusions permitted)&#xD;
  &#xD;
            -  Absolute neutrophil count (ANC) &gt;= 1500/mm^3&#xD;
  &#xD;
            -  Platelet count &gt;= 100,000/mm^3&#xD;
  &#xD;
            -  Creatinine (Cr) &lt; 2 x upper limit of normal (ULN), and Cr clearance (CrCl) &gt;= 50&#xD;
               mL/min by Cockcroft and Gault&#xD;
  &#xD;
            -  Alanine transaminase (ALT) and aspartate transaminase (AST) &lt; 2 x ULN (Patients with&#xD;
               liver metastases whose ALT/AST are &lt; 5 x ULN are eligible for enrollment)&#xD;
  &#xD;
            -  Bilirubin &lt; 2 x ULN&#xD;
  &#xD;
            -  White blood cell (WBC) count &gt; 2500/uL and &lt; 15000/uL&#xD;
  &#xD;
            -  Lymphocyte count &gt;= 500/uL&#xD;
  &#xD;
            -  Cardiac ejection fraction &gt;= 50%&#xD;
  &#xD;
            -  Negative serum pregnancy (human chorionic gonadotropin [beta-hCG]) test within 7 days&#xD;
               of day 0 (leukapheresis) for women of childbearing potential (WOCBP). WOCBP must be&#xD;
               willing to use a highly effective method of contraception for the course of the study&#xD;
               through 90 days after A2-ESO-1 TCR-engineered T cell infusion&#xD;
  &#xD;
            -  Willing and able to provide written informed consent for the study&#xD;
  &#xD;
            -  Willing to provide biopsy tissues and blood samples as required by the study&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Radiation therapy, chemotherapy, or non-cytotoxic investigational agent within 2 weeks&#xD;
               of day 0 (leukapheresis)&#xD;
  &#xD;
            -  Received cyclophosphamide within the past 4 months&#xD;
  &#xD;
            -  Evidence of New York Heart Association class III or greater cardiac disease&#xD;
  &#xD;
            -  History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic&#xD;
               conduction abnormality within the past 12 months&#xD;
  &#xD;
            -  History of congenital QT prolongation&#xD;
  &#xD;
            -  Absolute QT interval of &gt; 470 msec in the presence of &gt; 4.0 mEq/L potassium and &gt; 1.8&#xD;
               mg/dL magnesium&#xD;
  &#xD;
            -  Brain or leptomeningeal metastases&#xD;
  &#xD;
            -  Females who are pregnant or breastfeeding&#xD;
  &#xD;
            -  Hypersensitivity or intolerance to cyclophosphamide, fludarabine, or their components&#xD;
  &#xD;
            -  Alcoholic liver disease or other hepatic disease with the exception of liver&#xD;
               metastases&#xD;
  &#xD;
            -  History of gastrointestinal bleeding, ulceration, or perforation&#xD;
  &#xD;
            -  Any severe and/or uncontrolled medical conditions or other conditions that could&#xD;
               affect participation in the study, such as severely impaired lung function, any active&#xD;
               (acute or chronic) or uncontrolled infection/disorders, and non-malignant medical&#xD;
               illnesses that are uncontrolled or whose control may be jeopardized by the study&#xD;
               treatment&#xD;
  &#xD;
            -  Current use of medications that interact with or compromise the immune system such as&#xD;
               steroid doses &gt; 10 mg/day prednisone or equivalent daily within 2 weeks before&#xD;
               leukapheresis&#xD;
  &#xD;
            -  History of immunodeficiency disease or autoimmune disease&#xD;
  &#xD;
            -  Concurrent use of any complementary or alternative medicines&#xD;
  &#xD;
            -  Unwilling or unable to comply with the study protocol&#xD;
  &#xD;
            -  Prior major surgery that requires general anesthesia must be completed at least 4&#xD;
               weeks before leukapheresis and surgery that requires local anesthesia (except for&#xD;
               study tissue sample collection) must be completed at least 2 weeks before&#xD;
               leukapheresis&#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>Janice Lu, MD</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Southern California</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Kimberly Arieli, RN</last_name>
      <phone>323-865-3935</phone>
      <email>Kimberly.Arieli@med.usc.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>USC / Norris Comprehensive Cancer Center</name>
        <address>
          <city>Los Angeles</city>
          <state>California</state>
          <zip>90033</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Janice Lu</last_name>
        <phone>323-865-3000</phone>
      </contact>
      <investigator>
        <last_name>Janice Lu</last_name>
        <role>Principal Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>June 27, 2023</study_first_submitted>
    <study_first_submitted_qc>August 9, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 14, 2023</study_first_posted>
    <last_update_submitted>September 8, 2023</last_update_submitted>
    <last_update_submitted_qc>September 8, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 11, 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>Breast Neoplasms</mesh_term>
      <mesh_term>Triple Negative Breast Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Aldesleukin</mesh_term>
      <mesh_term>Cyclophosphamide</mesh_term>
      <mesh_term>Fludarabine</mesh_term>
      <mesh_term>Interleukin-2</mesh_term>
    </intervention_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05989828
  org study id: 1B-23-1
  secondary id: NCI-2023-04697
  secondary id: 1B-23-1
  secondary id: P30CA014089
  nct id: NCT05989828
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  This phase Ib trial tests the safety, side effects and best dose of anti-HLA-A2/NY-ESO-1
        T-cell receptor (TCR)-transduced autologous T lymphocytes (A2-ESO-1 TCR-T cells) in treating
        patients with NY-ESO-1 overexpression positive triple negative breast cancer (TNBC) that has
        come back after a period of improvement (relapsed/recurrent) or that does not respond to
        treatment (refractory), and that may have spread from where it first started (primary site)
        to nearby tissue, lymph nodes (advanced) or to other places in the body (metastatic).
        NY-ESO-1 is an antigen found on the surface of many different types of tumor cells including
        TNBC. Antigens make it possible for immune cells to recognize and kill germ cells that invade
        the body, however, it is more difficult for immune cells to recognize antigens on tumor
        cells. T cells are a special type of immune cell in the blood. These T cells may be trained
        to recognize the NY-ESO-1 antigen on tumor cells, allowing the T cells to attack and kill
        those tumor cells. The A2-ESO-1 TCR-T cells are T cells that have been removed from the
        patient's blood through a process called leukapheresis and then changed in the laboratory to
        recognize NY-ESO-1 on tumor cells. When given back to the patient, these A2-ESO-1 TCR-T cells
        find and attack tumor cells that express NY-ESO-1. Chemotherapy drugs, such as
        cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells,
        either by killing the cells, by stopping them from dividing, or by stopping them from
        spreading. They are given before the T cells to support optimum activity of the A2-ESO-1
        TCR-T cells. IL-2 (aldesleukin) is in a class of drugs known as cytokines. It is a man-made
        version of a naturally occurring protein that stimulates the body to produce other chemicals
        which increase the body's ability to fight cancer. A2-ESO-1 TCR-T cells may kill more tumor
        cells in patients with recurrent or refractory advanced or metastatic TNBC that overexpresses
        NY-ESO-1.
  PRIMARY OBJECTIVES:
  
        I. To determine the maximum tolerated dose (MTD) of anti-HLA-A2/NY-ESO-1 TCR-transduced
        autologous T lymphocytes (A2-ESO-1 TCR-engineered T cells) in patients with
        relapsed/refractory locally advanced or metastatic TNBC that overexpresses NY-ESO-1 by using
        the Bayesian optimal interval (BOIN) design.
  
        II. To determine the dose-limiting toxicities (DLTs) of A2-ESO-1 TCR-engineered T cells in
        patients with relapsed/refractory locally advanced or metastatic TNBC that overexpresses
        NY-ESO-1, as assessed by the National Cancer Institute Common Terminology Criteria for
        Adverse Events (NCI CTCAE) version (v)5.0.
  
        SECONDARY OBJECTIVES:
  
        I. To evaluate the antitumor activity of A2-ESO-1 TCR-engineered T cells, as assessed by the
        Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
  
        II. To evaluate the immunological activity (i.e., persistence, function) of A2-ESO-1
        TCR-engineered T cells.
  
        EXPLORATORY OBJECTIVE:
  
        I. To evaluate the correlative markers of A2-ESO-1 TCR-engineered T cells, including but not
        limited to PD-L1 expression and immune cell populations such as regulatory T cells (Tregs)
        and tumor-associated macrophages (TAMs).
  
        OUTLINE: This is a dose-escalation study of A2-ESO-1 TCR-T cells.
  
        Patients undergo leukapheresis on day -28 then receive cyclophosphamide intravenously (IV)
        over 1 hour on days -7 and -6 followed by fludarabine IV over 30 minutes on days -5 to -1.
        Patients then receive A2-ESO-1 TCR-T cells IV over 30 minutes on day 0 followed by
        aldesleukin IV over 15 minutes on days 0 to 2. Patients also undergo blood sample collection
        and computed tomography (CT) scans throughout the study. Additionally, patients may undergo a
        breast biopsy, a mammogram, breast magnetic resonance imaging (MRI), and breast ultrasound
        (US) at screening and follow up, and echocardiography (ECHO) or multi-gated acquisition scan
        (MUGA) at screening.
  
        After completion of study treatment, patients are followed up at 3, 6, and 12 months and then
        yearly for up to 15 years or until disease progression, voluntary study withdrawal or study
        discontinuation, whichever occurs first.
  allocation: N/A
  intervention model: Single Group Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Maximum tolerated dose (MTD) of anti-HLA-A2/NY-ESO-1 T-cell receptor (TCR)-transduced autologous T lymphocytes (A2-ESO-1 TCR-engineered T cells)
  time frame: Up to 8 weeks after A2-ESO-1 TCR-engineered T cell infusion
  description: Will employ the Bayesian optimal interval to find the MTD.
  measure: Incidence of dose-limiting toxicities
  time frame: Up to 8 weeks after A2 ESO-1 TCR-engineered T cell infusion
  description: Defined as any treatment-related death or any greater than or equal to grade 3 adverse event (AE) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.
  measure: Antitumor activity
  time frame: At pre-treatment and 6 months post-treatment
  description: Antitumor activity will be assessed by RECIST 1.1. Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) = at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum longest diameter as a reference, Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD) using the smallest sum longest diameter since treatment start as reference, PD = At least a ≥20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.
  measure: Change in PD-1 expression on T cells
  time frame: At pre-treatment and 6 months post-treatment
  description: Levels of PD-1 expression on T cells will be monitored. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.
  measure: Change in NY-ESO-1-specific TCR-engineered T cells
  time frame: At pre-treatment and 6 months post-treatment
  description: Levels of NY-ESO-1-specific TCR-engineered T cells will be monitored to determine whether these T cells are persistent. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.
  measure: Change in regulatory T cells (Treg)
  time frame: At pre-treatment and 6 months post-treatment
  description: Because NY-ESO-1-specific TCR-engineered CD4+ T cells may differentiate into Treg cells, levels of Treg cells will be monitored. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  arm group type: Experimental
  description: Patients undergo leukapheresis on day -28 then receive cyclophosphamide IV over 1 hour on days -7 and -6 followed by fludarabine IV over 30 minutes on days -5 to -1. Patients then receive A2-ESO-1 TCR-T cells IV over 30 minutes on day 0 followed by aldesleukin IV over 15 minutes on days 0 to 2. Patients also undergo blood sample collection and CT scans throughout the study. Additionally, patients may undergo a breast biopsy, a mammogram, breast MRI, and breast US at screening and follow up, and ECHO or MUGA at screening.
  intervention type: Biological
  intervention name: Aldesleukin
  description: Given IV
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: 125-L-Serine-2-133-interleukin 2
  other name: Proleukin
  other name: r-serHuIL-2
  other name: Recombinant Human IL-2
  other name: Recombinant Human Interleukin-2
  intervention type: Biological
  intervention name: Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes
  description: Given IV
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: Anti-HLA-A2/NY-ESO1 TCR-transduced Autologous T cells
  other name: Autologous Anti-HLA-A2/NY-ESO1 TCR-transduced T Lymphocytes
  other name: Autologous HLA-A2/NY-ESO-1-specific TCR Gene-transduced T-lymphocytes
  intervention type: Procedure
  intervention name: Biopsy
  description: Undergo biopsy of breast tumor
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: BIOPSY_TYPE
  other name: Bx
  intervention type: Procedure
  intervention name: Biospecimen Collection
  description: Undergo blood sample collection
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: Biological Sample Collection
  other name: Biospecimen Collected
  other name: Specimen Collection
  intervention type: Procedure
  intervention name: Computed Tomography
  description: Undergo CT scan
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: CAT
  other name: CAT Scan
  other name: Computed Axial Tomography
  other name: Computerized Axial Tomography
  other name: Computerized axial tomography (procedure)
  other name: Computerized Tomography
  other name: CT
  other name: CT Scan
  other name: tomography
  intervention type: Drug
  intervention name: Cyclophosphamide
  description: Given IV
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: (-)-Cyclophosphamide
  other name: 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
  other name: Carloxan
  other name: Ciclofosfamida
  other name: Ciclofosfamide
  other name: Cicloxal
  other name: Clafen
  other name: Claphene
  other name: CP monohydrate
  other name: CTX
  other name: CYCLO-cell
  other name: Cycloblastin
  other name: Cycloblastine
  other name: Cyclophospham
  other name: Cyclophosphamid monohydrate
  other name: Cyclophosphamide Monohydrate
  other name: Cyclophosphamidum
  other name: Cyclophosphan
  other name: Cyclophosphane
  other name: Cyclophosphanum
  other name: Cyclostin
  other name: Cyclostine
  other name: Cytophosphan
  other name: Cytophosphane
  other name: Cytoxan
  other name: Fosfaseron
  other name: Genoxal
  other name: Genuxal
  other name: Ledoxina
  other name: Mitoxan
  other name: Neosar
  other name: Revimmune
  other name: Syklofosfamid
  other name: WR- 138719
  intervention type: Procedure
  intervention name: Echocardiography
  description: Undergo ECHO
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: EC
  intervention type: Drug
  intervention name: Fludarabine
  description: Given IV
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: Fluradosa
  intervention type: Procedure
  intervention name: Leukapheresis
  description: Undergo leukapheresis
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: Leukocytopheresis
  other name: Therapeutic Leukopheresis
  intervention type: Procedure
  intervention name: Magnetic Resonance Imaging
  description: Undergo breast MRI
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: Magnetic Resonance
  other name: Magnetic resonance imaging (procedure)
  other name: Magnetic Resonance Imaging Scan
  other name: Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
  other name: MR
  other name: MR Imaging
  other name: MRI
  other name: MRI Scan
  other name: NMR Imaging
  other name: NMRI
  other name: Nuclear Magnetic Resonance Imaging
  intervention type: Procedure
  intervention name: Mammogram
  description: Undergo mammogram
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  intervention type: Procedure
  intervention name: Multigated Acquisition Scan
  description: Undergo MUGA scan
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: Blood Pool Scan
  other name: Equilibrium Radionuclide Angiography
  other name: Gated Blood Pool Imaging
  other name: Gated Heart Pool Scan
  other name: MUGA
  other name: MUGA Scan
  other name: Multi-Gated Acquisition Scan
  other name: Radionuclide Ventriculogram Scan
  other name: Radionuclide Ventriculography
  other name: RNVG
  other name: SYMA Scanning
  other name: Synchronized Multigated Acquisition Scanning
  intervention type: Procedure
  intervention name: Ultrasound Imaging
  description: Undergo ultrasound of breast
  arm group label: Treatment (A2-ESO-1 TCR-T cells)
  other name: 2-Dimensional Grayscale Ultrasound Imaging
  other name: 2-Dimensional Ultrasound Imaging
  other name: 2D-US
  other name: Ultrasonography
  other name: Ultrasound
  other name: Ultrasound Test
  other name: Ultrasound, Medical
  other name: US
  criteria: 
  gender: Female
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Janice Lu, MD
  role: Principal Investigator
  affiliation: University of Southern California
  last name: Kimberly Arieli, RN
  phone: 323-865-3935
  email: Kimberly.Arieli@med.usc.edu
  facility: 
  contact: 
  investigator: 
  country: United States
  responsible party type: Sponsor
  mesh term: Breast Neoplasms
  mesh term: Triple Negative Breast Neoplasms
  mesh term: Aldesleukin
  mesh term: Cyclophosphamide
  mesh term: Fludarabine
  mesh term: Interleukin-2