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

Korábbi kezelés

• Radiation therapy, chemotherapy, or non-cytotoxic investigational agent within 2 weeks of leukapheresis
• Received cyclophosphamide within the past 4 months
• 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
• Concurrent use of any complementary or alternative medicines
• 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 and surgery that requires local anesthesia (except for study tissue sample collection) must be completed at least 2 weeks before leukapheresis

Más betegség

• 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
• Hypersensitivity or intolerance to cyclophosphamide, fludarabine, IL-2, or their components
• History of clinically significant gastrointestinal bleeding, gastric or intestinal ulceration, or perforation within 6 months of enrollment.
• 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
• 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.
• Human immunodeficiency virus (HIV) infection or seropositive for HIV antigens

Laborértékek

• 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
• Active hepatitis B (as defined as positive hepBsAntigen or detectable hepatitis B DNA) or hepatitis C infection. Patients who are hepatitis B surface Antigen negative and have a negative hep B DNA are allowed. If hepatitis C antibody test is positive, then patients must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. Patients with laboratory evidence of cleared hepatitis B or C infection may enroll. Patients with no prior history of hepatitis B infection who have been vaccinated against hepatitis B and who have a positive antibody against hepatitis B surface antigen as the only evidence of prior exposure may enroll. Patients with a history of hepatitis C infection may be eligible if they have completed antiviral treatment and show no detectable HCV RNA for 6 months prior to enrollment.

Egyéb

• Brain or leptomeningeal metastases
• Females who are pregnant or breastfeeding
• Unwilling or unable to comply with the study protocol

• 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. 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
• Lymphocyte count >= 500/uL
• Cardiac left ventricular ejection fraction (LVEF) >= 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