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Triple Negative Breast CancerPhase 1NCT05989828

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

A Phase 1 study testing Aldesleukin, Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes and Biopsy in people with Triple Negative Breast Cancer, run by University of Southern California at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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… Read more about this study

Who is it for?
Ages 18 years and older, women only
Conditions the study is for
Triple Negative Breast Cancer
What is being tested?
Aldesleukin, Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes and Biopsy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
17 Dec 2024to 31 Dec 2028
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 19Show fewer
  • 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

Who cannot join

  • 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
Show all 19Show fewer
  • 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

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kimberly Arieli, RN contact

323-865-3935

Kimberly.Arieli@med.usc.edu

United States1 site, 1 recruiting

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

    Kimberly Arieli, RN, 323-865-0451, Kimberly.Arieli@med.usc.edu

    Daphne Stewart, MD

    Recruiting

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Aldesleukin, Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes, Biopsy, Biospecimen Collection, Computed Tomography
Medical subject headings
Triple Negative Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AldesleukinBiological

    Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2

    Given IV

  • Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T LymphocytesBiological

    Also called 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

    Given IV

  • BiopsyProcedure or surgery

    Also called BIOPSY_TYPE, Bx

    Undergo biopsy of breast tumor

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo blood sample collection

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT scan

  • CyclophosphamideDrug

    Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida

    Given IV

  • EchocardiographyProcedure or surgery

    Also called EC

    Undergo ECHO

  • FludarabineDrug

    Also called Fluradosa

    Given IV

  • LeukapheresisProcedure or surgery

    Also called Leukocytopheresis, Therapeutic Leukopheresis

    Undergo leukapheresis

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance

    Undergo breast MRI

  • MammogramProcedure or surgery

    Undergo mammogram

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • Ultrasound ImagingProcedure or surgery

    Also called 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography

    Undergo ultrasound of breast

Study groups in NCT05989828
Study groupRoleWhat they receive
Treatment (A2-ESO-1 TCR-T cells)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Up to 6 weeks after A2-ESO-1 TCR-engineered T cell infusion

  2. 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.

    Measured: Up to 6 weeks after A2 ESO-1 TCR-engineered T cell infusion

Secondary outcomes (4)

  1. Antitumor activity

    Antitumor activity will be assessed by RECIST 1.1. Complete Response (CR) = disappearance of all target lesions, Partial Response (PR) = at least a 30% decrease in the sum of the longest diameter of target lesions, using the baseline sum longest diameter as a reference, Stable Disease (SD) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD) using the smallest sum longest diameter since treatment start as reference, PD = At least a ≥20% increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.

    Measured: At pre-treatment and 6 months post-treatment

  2. Change in PD-1 expression on T cells

    Levels of PD-1 expression on T cells will be monitored. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.

    Measured: At pre-treatment and 6 months post-treatment

  3. Change in NY-ESO-1-specific TCR-engineered T cells

    Levels of NY-ESO-1-specific TCR-engineered T cells will be monitored to determine whether these T cells are persistent. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.

    Measured: At pre-treatment and 6 months post-treatment

  4. Change in regulatory T cells (Treg)

    Because NY-ESO-1-specific TCR-engineered CD4+ T cells may differentiate into Treg cells, levels of Treg cells will be monitored. Post-treatment biomarker measurements will be compared to the pre-treatment values using a one-sided paired t-test and nonparametric Wilcoxon signed-rank test.

    Measured: At pre-treatment and 6 months post-treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Aug 2023
  2. Study start17 Dec 2024
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05989828
Sponsor's protocol ID
1B-23-1
Other IDs
NCI-2023-04697, 1B-23-1, P30CA014089
Status last verified
May 2026
First submitted
27 Jun 2023
Last updated
19 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Aldesleukin, Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes and Biopsy in people with Triple Negative Breast Cancer, run by University of Southern California at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kimberly Arieli, RN (323-865-3935, Kimberly.Arieli@med.usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: Up to 6 weeks after A2-ESO-1 TCR-engineered T cell infusion). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05989828.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 May 2026.

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