Engineered T cells for treating advanced triple negative breast cancer
Phase Ib Clinical Trial of Autologous Anti-NY-ESO-1 TCR-Engineered T Cells in Patients With Relapsed/Refractory Locally Advanced or Metastatic NY-ESO-1-Expressing Triple Negative Breast Cancer
This study is testing a new treatment using specially engineered T cells to see if it can help people with advanced triple negative breast cancer that has come back or does not respond to other treatments.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 20 (estimated) |
| Ages | 18 Years and up |
| Sex | Female |
| Sponsor | University of Southern California Academic / other |
| Drugs / interventions | trastuzumab, chemotherapy, Radiation, cyclophosphamide, fludarabine, prednisone |
| Locations | 1 site (Los Angeles, California) |
| Trial ID | NCT05989828 on ClinicalTrials.gov |
What this trial studies
This phase Ib trial evaluates the safety and optimal dosing of A2-ESO-1 TCR-engineered T cells in patients with relapsed or refractory advanced or metastatic triple negative breast cancer (TNBC) that overexpresses the NY-ESO-1 antigen. The study employs a dose-escalation design to determine the maximum tolerated dose and assess dose-limiting toxicities. Patients will undergo leukapheresis to collect T cells, which will then be engineered to target the NY-ESO-1 antigen before being infused back into the patient. The trial also aims to evaluate the antitumor activity and immunological persistence of these engineered T cells.
Who should consider this trial
Good fit: Ideal candidates are females aged 18 and older with advanced or metastatic TNBC that has relapsed or is refractory to multiple lines of therapy and who express the NY-ESO-1 antigen.
Not a fit: Patients with TNBC that does not overexpress NY-ESO-1 or those who have not received at least two lines of prior therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this approach could provide a novel immunotherapy option for patients with advanced triple negative breast cancer that is resistant to standard treatments.
How similar studies have performed: Other studies using engineered T cells targeting specific tumor antigens have shown promising results, indicating potential for success in this novel approach.
Eligibility criteria
Show full inclusion / exclusion 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 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 day 0 (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 day 0 (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 * 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
Where this trial is running
Los Angeles, California
- USC / Norris Comprehensive Cancer Center — Los Angeles, California, United States (Recruiting)
Study contacts
- Principal investigator: Daphne Stewart, MD — University of Southern California
- Study coordinator: Kimberly Arieli, RN
- Email: Kimberly.Arieli@med.usc.edu
- Phone: 323-865-3935
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.