Status:
RECRUITING
A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer
Lead Sponsor:
University of Southern California
Collaborating Sponsors:
National Cancer Institute (NCI)
Conditions:
Triple Negative Breast Cancer
Eligibility:
FEMALE
18+ years
Phase:
PHASE1
Brief Summary
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-E...
Detailed Description
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/refrac...
Eligibility Criteria
Inclusion
- 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
- 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 RT-PCR and be HCV 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 and surgery that requires local anesthesia (except for study tissue sample collection) must be completed at least 2 weeks before leukapheresis
Key Trial Info
Start Date :
December 17 2024
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
December 17 2027
Estimated Enrollment :
20 Patients enrolled
Trial Details
Trial ID
NCT05989828
Start Date
December 17 2024
End Date
December 17 2027
Last Update
January 7 2026
Active Locations (1)
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1
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States, 90033