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

Triple Negative Breast Cancer Clinical Trial

Official title: 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

Status Not yet recruiting

Clinical Trial 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.

Clinical Trial 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/refractory locally advanced or metastatic TNBC that overexpresses NY-ESO-1 by using the Bayesian optimal interval (BOIN) design.

II. To determine the dose-limiting toxicities (DLTs) of A2-ESO-1 TCR-engineered T cells in patients with relapsed/refractory locally advanced or metastatic TNBC that overexpresses NY-ESO-1, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version (v)5.0.

SECONDARY OBJECTIVES:

I. To evaluate the antitumor activity of A2-ESO-1 TCR-engineered T cells, as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.

II. To evaluate the immunological activity (i.e., persistence, function) of A2-ESO-1 TCR-engineered T cells.

EXPLORATORY OBJECTIVE:

I. To evaluate the correlative markers of A2-ESO-1 TCR-engineered T cells, including but not limited to PD-L1 expression and immune cell populations such as regulatory T cells (Tregs) and tumor-associated macrophages (TAMs).

OUTLINE: This is a dose-escalation study of A2-ESO-1 TCR-T cells.

Patients undergo leukapheresis on day -28 then receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 followed by fludarabine IV over 30 minutes on days -5 to -1. Patients then receive A2-ESO-1 TCR-T cells IV over 30 minutes on day 0 followed by aldesleukin IV over 15 minutes on days 0 to 2. Patients also undergo blood sample collection and computed tomography (CT) scans throughout the study. Additionally, patients may undergo a breast biopsy, a mammogram, breast magnetic resonance imaging (MRI), and breast ultrasound (US) at screening and follow up, and echocardiography (ECHO) or multi-gated acquisition scan (MUGA) at screening.

After completion of study treatment, patients are followed up at 3, 6, and 12 months and then yearly for up to 15 years or until disease progression, voluntary study withdrawal or study discontinuation, whichever occurs first. ;

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Cancer
• Triple Negative Breast Neoplasms

• NCT number: NCT05989828
• Study type: Interventional
• Source: University of Southern California
• Contact: Kimberly Arieli, RN
• Phone: 323-865-3935
• Email: Kimberly.Arieli@med.usc.edu
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 1, 2024
• Completion date: August 1, 2027