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

NCT05989828 | Suspended Phase 1 DMC FDA Drug

• 3 other identifiers: 1B-23-1NCI-2023-04697P30CA014089
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of anti-HLA-A2/NY-ESO-1 T-cell receptor (TCR)-transduced autologous T lymphocytes (A2-ESO-1 TCR-engineered T cells)

  Will employ the Bayesian optimal interval to find the MTD.

  Up to 8 weeks after A2-ESO-1 TCR-engineered T cell infusion

• Incidence of dose-limiting toxicities

  Defined as any treatment-related death or any greater than or equal to grade 3 adverse event (AE) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0.

  Up to 8 weeks after A2 ESO-1 TCR-engineered T cell infusion

Secondary Outcomes (4)

• Antitumor activity

  At pre-treatment and 6 months post-treatment

• Change in PD-1 expression on T cells

  At pre-treatment and 6 months post-treatment

• Change in NY-ESO-1-specific TCR-engineered T cells

  At pre-treatment and 6 months post-treatment

• Change in regulatory T cells (Treg)

  At pre-treatment and 6 months post-treatment

Study Arms (1)

Treatment (A2-ESO-1 TCR-T cells)

EXPERIMENTAL

Patients undergo leukapheresis on day -28 then receive cyclophosphamide 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 CT scans throughout the study. Additionally, patients may undergo a breast biopsy, a mammogram, breast MRI, and breast US at screening and follow up, and ECHO or MUGA at screening.

Biological: Aldesleukin; Biological: Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes; Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Cyclophosphamide; Procedure: Echocardiography; Drug: Fludarabine; Procedure: Leukapheresis; Procedure: Magnetic Resonance Imaging; Procedure: Mammogram; Procedure: Multigated Acquisition Scan; Procedure: Ultrasound Imaging

Interventions

Aldesleukin BIOLOGICAL

Given IV

Also known as: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2, Recombinant Human Interleukin-2

Treatment (A2-ESO-1 TCR-T cells)

Biopsy PROCEDURE

Undergo biopsy of breast tumor

Also known as: BIOPSY_TYPE, Bx

Treatment (A2-ESO-1 TCR-T cells)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (A2-ESO-1 TCR-T cells)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, CT, CT Scan, tomography

Treatment (A2-ESO-1 TCR-T cells)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719

Treatment (A2-ESO-1 TCR-T cells)

Echocardiography PROCEDURE

Undergo ECHO

Also known as: EC

Treatment (A2-ESO-1 TCR-T cells)

Fludarabine DRUG

Given IV

Also known as: Fluradosa

Treatment (A2-ESO-1 TCR-T cells)

Leukapheresis PROCEDURE

Undergo leukapheresis

Also known as: Leukocytopheresis, Therapeutic Leukopheresis

Treatment (A2-ESO-1 TCR-T cells)

Magnetic Resonance Imaging PROCEDURE

Undergo breast MRI

Also known as: Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging

Treatment (A2-ESO-1 TCR-T cells)

Mammogram PROCEDURE

Undergo mammogram

Treatment (A2-ESO-1 TCR-T cells)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (A2-ESO-1 TCR-T cells)

Ultrasound Imaging PROCEDURE

Undergo ultrasound of breast

Also known as: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography, Ultrasound, Ultrasound Test, Ultrasound, Medical, US

Treatment (A2-ESO-1 TCR-T cells)

Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes BIOLOGICAL

Given IV

Also known as: Anti-HLA-A2/NY-ESO1 TCR-transduced Autologous T cells, Autologous Anti-HLA-A2/NY-ESO1 TCR-transduced T Lymphocytes, Autologous HLA-A2/NY-ESO-1-specific TCR Gene-transduced T-lymphocytes

Treatment (A2-ESO-1 TCR-T cells)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Southern California: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

aldesleukin; Biopsy; Specimen Handling; Cyclophosphamide; fludarabine; Leukapheresis; Magnetic Resonance Spectroscopy; High-Energy Shock Waves

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Spectrum Analysis; Chemistry Techniques, Analytical; Ultrasonic Waves; Sound; Radiation, Nonionizing; Radiation; Physical Phenomena

Study Officials

• Daphne Stewart, MD

  University of Southern California

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2023
• First Posted: August 14, 2023
• Study Start: December 17, 2024
• Primary Completion (Estimated): December 17, 2026
• Study Completion (Estimated): December 17, 2027
• Last Updated: January 14, 2026

Record last verified: 2026-01

Locations

US (1)