A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer

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.