Autologous Anti-NY-ESO-1 TCR-Engineered T Cells for the Treatment of Patients with Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer

Inclusion Criteria

• Female aged >= 18 years
• Histologically confirmed advanced or metastatic TNBC that have relapsed on or are refractory to 2 or more lines of standard-of-care therapy including immune checkpoint inhibitors, chemotherapy, trastuzumab deruxtecan (TDX-d) and poly-ADP ribose polymerase (PARP) inhibitors if indicated, but less than 4 lines of total therapies. TNBC is defined as estrogen receptor (ER) and progesterone receptor negative (< 10% immunohistochemistry [IHC] staining) and HER2 negative (IHC 1+ or 0 AND/OR in situ hybridization negative based on: * Single-probe average HER2 copy number < 4.0 signals/cell * Dual-probe HER2/CEP17 ratio < 2.0 with an average HER2 copy number < 4.0 signals/cell)
• HLA-A2+ and tumoral overexpression of NY-ESO-1 (2 to 3+ IHC staining in > 50% of cells)
• Have measurable disease based on RECIST 1.1
• Life expectancy >= 6 months
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Hemoglobin >= 9.0 g/dL (transfusions permitted)
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelet count >= 100,000/mm^3
• Creatinine (Cr) < 2 x upper limit of normal (ULN), and Cr clearance (CrCl) >= 50 mL/min by Cockcroft and Gault
• Alanine transaminase (ALT) and aspartate transaminase (AST) < 2 x ULN (Patients with liver metastases whose ALT/AST are < 5 x ULN are eligible for enrollment)
• Bilirubin < 2 x ULN
• White blood cell (WBC) count > 2500/uL and < 15000/uL
• Lymphocyte count >= 500/uL
• Cardiac ejection fraction >= 50%
• Negative serum pregnancy (human chorionic gonadotropin [beta-hCG]) test within 7 days of leukapheresis for women of childbearing potential (WOCBP). WOCBP must be willing to use a highly effective method of contraception for the course of the study through 90 days after A2-ESO-1 TCR-engineered T cell infusion
• Willing and able to provide written informed consent for the study
• Willing to provide biopsy tissues and blood samples as required by the study

Exclusion Criteria

• Radiation therapy, chemotherapy, or non-cytotoxic investigational agent within 2 weeks of leukapheresis
• Received cyclophosphamide within the past 4 months
• Evidence of New York Heart Association class III or greater cardiac disease
• History of myocardial infarction, stroke, ventricular arrhythmia, or symptomatic conduction abnormality within the past 12 months
• History of congenital QT prolongation
• Absolute QT interval of > 470 msec in the presence of > 4.0 mEq/L potassium and > 1.8 mg/dL magnesium
• Brain or leptomeningeal metastases
• Females who are pregnant or breastfeeding
• Hypersensitivity or intolerance to cyclophosphamide, fludarabine, or their components
• Alcoholic liver disease or other hepatic disease with the exception of liver metastases
• History of gastrointestinal bleeding, ulceration, or perforation
• Any severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study, such as severely impaired lung function, any active (acute or chronic) or uncontrolled infection/disorders, and non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the study treatment
• Current use of medications that interact with or compromise the immune system such as steroid doses > 10 mg/day prednisone or equivalent daily within 2 weeks before leukapheresis
• History of immunodeficiency disease or autoimmune disease with exceptions such as Hashimoto’s thyroiditis / hypothyroidism, or controlled Type 1 diabetes
• Have any active and uncontrolled infection
• Active hepatitis B or hepatitis C infection or seropositive for hepatitis B, and hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by real time polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative
• Human immunodeficiency virus (HIV) infection or seropositive for HIV antigens
• Concurrent use of any complementary or alternative medicines
• Unwilling or unable to comply with the study protocol
• Prior major surgery that requires general anesthesia must be completed at least 4 weeks before leukapheresis and surgery that requires local anesthesia (except for study tissue sample collection) must be completed at least 2 weeks before leukapheresis