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

Launched by UNIVERSITY OF SOUTHERN CALIFORNIA · Aug 9, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a new treatment for women with advanced or metastatic triple negative breast cancer (TNBC) that has returned after treatment or did not respond to previous therapies. The study focuses on using specially modified immune cells called T cells, which are taken from the patient's own blood and trained in a lab to recognize a specific protein (NY-ESO-1) found on some tumor cells. By doing this, the goal is to help the immune system better target and attack the cancer cells. Participants will also receive chemotherapy drugs before the T cells are given back to them to enhance the treatment's effectiveness.

To be eligible for this trial, women aged 18 and older with confirmed advanced or metastatic TNBC that has not responded to at least two types of standard treatments may qualify. They should have certain characteristics, such as specific test results indicating their cancer expresses the NY-ESO-1 protein. During the trial, participants can expect to undergo a process to collect their T cells, receive the modified cells, and have regular monitoring for safety and effectiveness. It’s important to note that there are specific health criteria that must be met, and those interested should discuss their individual situations with their healthcare team.

Gender

FEMALE

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 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 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