Trial Title:
A2-ESO-1 TCR-Engineered T Cells for Relapsed/Refractory Advanced or Metastatic NY-ESO-1 Overexpression Positive Triple Negative Breast Cancer
NCT ID:
NCT05989828
Condition:
Triple Negative Breast Cancer
Conditions: Official terms:
Breast Neoplasms
Triple Negative Breast Neoplasms
Aldesleukin
Cyclophosphamide
Fludarabine
Interleukin-2
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Aldesleukin
Description:
Given IV
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
125-L-Serine-2-133-interleukin 2
Other name:
Proleukin
Other name:
r-serHuIL-2
Other name:
Recombinant Human IL-2
Other name:
Recombinant Human Interleukin-2
Intervention type:
Biological
Intervention name:
Anti-HLA-A2/NY-ESO-1 TCR-transduced Autologous T Lymphocytes
Description:
Given IV
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
Anti-HLA-A2/NY-ESO1 TCR-transduced Autologous T cells
Other name:
Autologous Anti-HLA-A2/NY-ESO1 TCR-transduced T Lymphocytes
Other name:
Autologous HLA-A2/NY-ESO-1-specific TCR Gene-transduced T-lymphocytes
Intervention type:
Procedure
Intervention name:
Biopsy
Description:
Undergo biopsy of breast tumor
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
BIOPSY_TYPE
Other name:
Bx
Intervention type:
Procedure
Intervention name:
Biospecimen Collection
Description:
Undergo blood sample collection
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
Biological Sample Collection
Other name:
Biospecimen Collected
Other name:
Specimen Collection
Intervention type:
Procedure
Intervention name:
Computed Tomography
Description:
Undergo CT scan
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
CAT
Other name:
CAT Scan
Other name:
Computed Axial Tomography
Other name:
Computerized Axial Tomography
Other name:
Computerized axial tomography (procedure)
Other name:
Computerized Tomography
Other name:
CT
Other name:
CT Scan
Other name:
tomography
Intervention type:
Drug
Intervention name:
Cyclophosphamide
Description:
Given IV
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
(-)-Cyclophosphamide
Other name:
2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
Other name:
Carloxan
Other name:
Ciclofosfamida
Other name:
Ciclofosfamide
Other name:
Cicloxal
Other name:
Clafen
Other name:
Claphene
Other name:
CP monohydrate
Other name:
CTX
Other name:
CYCLO-cell
Other name:
Cycloblastin
Other name:
Cycloblastine
Other name:
Cyclophospham
Other name:
Cyclophosphamid monohydrate
Other name:
Cyclophosphamide Monohydrate
Other name:
Cyclophosphamidum
Other name:
Cyclophosphan
Other name:
Cyclophosphane
Other name:
Cyclophosphanum
Other name:
Cyclostin
Other name:
Cyclostine
Other name:
Cytophosphan
Other name:
Cytophosphane
Other name:
Cytoxan
Other name:
Fosfaseron
Other name:
Genoxal
Other name:
Genuxal
Other name:
Ledoxina
Other name:
Mitoxan
Other name:
Neosar
Other name:
Revimmune
Other name:
Syklofosfamid
Other name:
WR- 138719
Intervention type:
Procedure
Intervention name:
Echocardiography
Description:
Undergo ECHO
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
EC
Intervention type:
Drug
Intervention name:
Fludarabine
Description:
Given IV
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
Fluradosa
Intervention type:
Procedure
Intervention name:
Leukapheresis
Description:
Undergo leukapheresis
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
Leukocytopheresis
Other name:
Therapeutic Leukopheresis
Intervention type:
Procedure
Intervention name:
Magnetic Resonance Imaging
Description:
Undergo breast MRI
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
Magnetic Resonance
Other name:
Magnetic resonance imaging (procedure)
Other name:
Magnetic Resonance Imaging Scan
Other name:
Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance
Other name:
MR
Other name:
MR Imaging
Other name:
MRI
Other name:
MRI Scan
Other name:
NMR Imaging
Other name:
NMRI
Other name:
Nuclear Magnetic Resonance Imaging
Intervention type:
Procedure
Intervention name:
Mammogram
Description:
Undergo mammogram
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Intervention type:
Procedure
Intervention name:
Multigated Acquisition Scan
Description:
Undergo MUGA scan
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
Blood Pool Scan
Other name:
Equilibrium Radionuclide Angiography
Other name:
Gated Blood Pool Imaging
Other name:
Gated Heart Pool Scan
Other name:
MUGA
Other name:
MUGA Scan
Other name:
Multi-Gated Acquisition Scan
Other name:
Radionuclide Ventriculogram Scan
Other name:
Radionuclide Ventriculography
Other name:
RNVG
Other name:
SYMA Scanning
Other name:
Synchronized Multigated Acquisition Scanning
Intervention type:
Procedure
Intervention name:
Ultrasound Imaging
Description:
Undergo ultrasound of breast
Arm group label:
Treatment (A2-ESO-1 TCR-T cells)
Other name:
2-Dimensional Grayscale Ultrasound Imaging
Other name:
2-Dimensional Ultrasound Imaging
Other name:
2D-US
Other name:
Ultrasonography
Other name:
Ultrasound
Other name:
Ultrasound Test
Other name:
Ultrasound, Medical
Other name:
US
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.
Detailed 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.
Criteria for 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 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
Gender:
Female
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
USC / Norris Comprehensive Cancer Center
Address:
City:
Los Angeles
Zip:
90033
Country:
United States
Contact:
Last name:
Kimberly Arieli, RN
Phone:
323-865-0451
Email:
Kimberly.Arieli@med.usc.edu
Investigator:
Last name:
Daphne Stewart, MD
Email:
Principal Investigator
Start date:
October 1, 2024
Completion date:
October 1, 2027
Lead sponsor:
Agency:
University of Southern California
Agency class:
Other
Collaborator:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
University of Southern California
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05989828
