Gene-Modified T Cells in Treating Patients With Locally Advanced or Stage IV Solid Tumors Expressing NY-ES0-1

PRIMARY OBJECTIVES:

I. To evaluate the safety and feasibility of adoptive transfer of autologous NY-ESO-1 T cell
receptor (TCR) (NY-ESO-1 reactive TCR retroviral vector transduced autologous
PBL)/dominant-negative transforming growth factor-beta receptor II (dnTGFbetaRII)
(TGFbDNRII-transduced autologous tumor infiltrating lymphocytes [TILs]) transgenic T cells in
combination with Decitabine.

SECONDARY OBJECTIVES:

I. NY-ESO-1 TCR/ dnTGFβRII transgenic T cell persistence by analyzing serial peripheral blood
samples for the presence of T cells with the NY-ESO-1 TCR by tetramer analysis.

II. To study T cell differentiation that correlates with higher anti-tumor responses.

III. Assess clinical response and progression free survival.

OUTLINE: This is a phase I, dose-escalation study of NY-ESO-1 TCR/TGFbDNRII-transduced TILs
followed by a phase II study.

Patients receive cyclophosphamide intravenously (IV) over 2 hours on days -5 and -4. Patients
then receive NY-ESO-1 reactive TCR retroviral vector transduced autologous PBL with
TGFbDNRII-transduced autologous TILs infusion on day 0.

After completion of study treatment, patients are follow up at weeks 1-4, 8 and 12, at 6 and
9 months, every 6 months for 5 years, and yearly for 9 years.

Inclusion Criteria:

- Solid tumors refractory to treatment that are either Stage IV or locally advanced

- For cohorts 1, 2 and 3 only - Patient's tumor must be positive by histological or
molecular assay for NY-ES0-1, according to the screening algorithm under "tumor
biopsy". Historical results may be used.

- For Cohort 4 - NY-ESO-1 results will be noted but NY-ESO-1 positivity not required for
eligibility.

- Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping
(blood test or buccal swab). Historical documentation acceptable.

- Life expectancy greater than 3 months assessed by a study physician

- Have been informed of other treatment options

- A minimum of one measurable lesion defined as:

- Meeting the criteria for measurable disease according to Immune-Related Response
Evaluation Criteria in Solid Tumors (irRECIST)

- For patients with skin metastases, lesions selected as non-completely biopsied
target lesion(s) that can be accurately measured and recorded by color
photography with a ruler to document the size of the target lesion(s)

- No restriction based on prior treatments but at least 4 weeks from prior
immunotherapy, or prior investigational agents

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

- Must have adequate venous access for apheresis

- Women of childbearing potential and men are requested to use acceptable methods of
birth control for the duration of the study and 6 months after; methods for acceptable
birth control include: condoms, diaphragm or cervical cap with spermicide,
intrauterine device, and hormonal contraception; it is recommended that a combination
of two methods be used

- Leukocytes: >=3,000/mcl (lymphocyte [lymph] %: >= 10%)

- Absolute neutrophil count: >= 1,000/mcl

- Platelets: >= 100,000/mcl

- Total bilirubin: =< 1.5 upper limit of normal (ULN)

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]):
=< 2.5 x institutional upper limit of normal

- Creatinine: =< 2X ULN; if creatinine > 2X ULN

- Creatinine clearance: must be > 60 ml/min

- Must be willing and able to accept the leukapheresis procedure

- At screening, must have tissue available for NY-ESO-1 testing (if not previously
performed) or be willing and able to undergo a fresh tissue biopsy.

- Patient must understand the investigational nature of this study and sign an
Independent Ethics Committee/Institutional Review Board approved written informed
consent form prior to receiving any study related procedure

- Participant must agree to and arrange for a caregiver (age >= 18 years) available 24
hours a day/7 days a week and arrange for lodging within 45 minute drive to Roswell
Park and transportation for a period of time after discharge from the hospital. The
exact amount of time will depend on the individual status as determined by the
treating physician.

Exclusion Criteria:

- Previously known hypersensitivity to any of the agents used in this study

- Currently receiving any other investigational agents

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements..EKG will be done at screening. Cardiac stress test will be done as
clinically indicated, specific test to be chosen at the discretion of the treating
physician

- History of severe autoimmune disease requiring steroids or other immunosuppressive
treatments

- History of inflammatory bowel disease, celiac disease, or other chronic
gastrointestinal conditions associated with diarrhea or bleeding, or current acute
colitis of any origin

- Potential requirement for systemic corticosteroids or concurrent immunosuppressive
drugs based on prior history or received systemic steroids within the last 4 weeks
prior to enrollment (inhaled or topical steroids at standard doses or isolated use of
steroids as premedication for medical procedures to minimize allergic reaction (e.g.
CT scan dye)are allowed)

- Known active infection with human immunodeficiency virus (HIV), hepatitis B, hepatitis
C or cytomegalovirus (CMV)

- Known cases of clinically active brain metastases (brain MRI as clinically indicated);
prior evidence of brain metastasis successfully treated with surgery or radiation
therapy will not be exclusion for participation as long as they are deemed under
control at the time of study enrollment

- Dementia or significantly altered mental status that would prohibit the understanding
or rendering of informed consent and compliance with the requirements of this protocol

- Pregnancy or breast-feeding; female patients must be surgically sterile or be
postmenopausal for two years, or must agree to use effective contraception during the
period of treatment and 6 months after; all female patients with reproductive
potential must have a negative pregnancy test (serum/urine) within 48 hours from
starting the conditioning chemotherapy

- Lack of availability of a patient for immunological and clinical follow-up assessment