NCT05989828 A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer
| NCT ID | NCT05989828 |
| Status | Recruiting |
| Phase | Phase 1 |
| Sponsor | University of Southern California |
| Condition | Triple Negative Breast Cancer |
| Study Type | INTERVENTIONAL |
| Enrollment | 20 participants |
| Start Date | 2024-12-17 |
| Primary Completion | 2027-12-31 |
Eligibility & Interventions
Eligibility Fast-Check
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
Phase 1 is the earliest stage of human testing — safety and dosage are the primary focus. Visits are frequent and medical supervision is intensive. You will be among the first people to receive this treatment.
This trial targets 20 participants in total. It began in 2024-12-17 with a primary completion date of 2027-12-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
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-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.
Eligibility Criteria
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. 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 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, 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 * 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 (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. * 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
Contact & Investigator
Daphne Stewart, MD
PRINCIPAL INVESTIGATOR
University of Southern California
Frequently Asked Questions
Who can join the NCT05989828 clinical trial?
This trial is open to female participants only, aged 18 Years or older, studying Triple Negative Breast Cancer. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
What phase is the NCT05989828 trial and what does that mean for participants?
Phase 1 trials are the first stage of human testing. The primary goal is to assess safety and determine appropriate dosage levels. Participants are closely monitored. These trials typically involve a small number of volunteers.
Is NCT05989828 currently recruiting?
Yes, NCT05989828 is actively recruiting participants. Contact the research team at Kimberly.Arieli@med.usc.edu for enrollment information.
Where is the NCT05989828 trial being conducted?
This trial is being conducted at Los Angeles, United States.
Who is sponsoring the NCT05989828 clinical trial?
NCT05989828 is sponsored by University of Southern California. The principal investigator is Daphne Stewart, MD at University of Southern California. The trial plans to enroll 20 participants.
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