Brief Title: Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: Safety profile (i.e. adverse events

Primary Outcome 1 - Timeframe: 8 weeks

Primary Outcome 2 - Measure: presence/absence of RCR

Primary Outcome 2 - Timeframe: 8 weeks

Primary Outcome 3 - Measure: analysis of clonality and PK of TBI-1301) assessed by CTCAE v.4.0 and laboratory testings.

Primary Outcome 3 - Timeframe: N/A

Primary Outcome 4 - Measure: Recommended phase 2 (RP2D) dose o TBI-1301 when administered following cyclophosphamide and fludarabine pre-treatment

Primary Outcome 4 - Timeframe: N/A

CONDITION

• NY-ESO-1 Expressing Solid Tumors in HLA-A2 Positive Patients
• Synovial Sarcoma
• Melanoma
• Esophageal Cancer
• Ovarian Cancer
• Lung Cancer
• Bladder Cancer
• Liver Cancer

ELIGIBILITY

Inclusion Criteria:
* Histologically or cytologically confirmed metastatic or recurrent unresectable solid tumor.

- * HLA-A*02:01 or HLA-A*02:06 positive.

- * Tumor NY-ESO-1 expression by immunohistochemistry.

- * No anti-cancer chemotherapy, radiation therapy or immunotherapy within 2 weeks or 5 half-lives of PBMC harvest.

- * The treating investigator should consider the patient to have disease that is incurable and that the patient would be a reasonable candidate for future treatment with TBI-1301.

- * Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >10 mm with CT scan, MRI, or calipers by clinical exam. Patients must have radiographic evidence of disease progression following the most recent line of treatment. Areas of previous radiation may not serve as measurable disease unless there is evidence of progression post radiation.

- * ECOG Performance Status 0 or 1.

- * Age ≥16 years on consent.

- * Life expectancy greater than 4 months.

- * The following laboratory requirements must be met (within 14 days prior to phlebotomy for generation of TBI-1301):

- * Absolute neutrophil count (ANC) ≥1.5 x10^9/L (1500/μL) without G-CSF support

- * WBC ≥ 2.5x10^9/L (2,500/μl)

- * Lymphocytes ≥ 0.5x10^9/L (500/μl)

- * Hemoglobin ≥ 80 g/L

- * Platelets ≥ 75x10^9/L (75,000/μl)

- * Total bilirubin ≤ 1.5 x upper limit of normal (ULN) (≤2.5X if Gilbert's disease)

- * AST(SGOT), ALT(SGPT) < 3.0 x ULN (< 5 x ULN with known liver metastases) - * Creatinine ≥ 60 ml/min (calculated by Cockcroft and Gault) - * Adequate renal function - * Consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
Exclusion Criteria:
* Uncontrolled intercurrent illnesses or medical conditions that may interfere with trial participation such as ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, severe active peptic ulcer disease or gastritis, or psychiatric illness/social situations that would limit compliance with study requirement or compromise the ability of the subject to give written informed consent.

- * Patients who are receiving any other investigational agents.

- * Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects with vitiligo, Grave's disease, Hashimoto's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.

- * Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

- * No evidence of active uncontrolled infection (patients on antibiotics are eligible).

- * History of primary immunodeficiency.

- * History of organ transplant that requires use of immunosuppressives.

- * Known allergy or reaction to a known component of TBI-1301.

- * Untreated central nervous system metastases requiring concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids. If treated lesions are shown to be stable for 1 month the subject may be eligible.

- * Other invasive malignancy within 2 years except for noninvasive malignancies such as cervical carcinoma in situ, non-melanomatous carcinoma of the skin or ductal carcinoma in situ of the breast that has/have been surgically cured.

- * Current or prior use of immunosuppressive medication within 14 days before phlebotomy, with the exceptions of intranasal, topical, and inhaled corticosteroids or systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent. Oral steroid use as premedication to prevent allergic reactions to radiologic contrast is allowed.

- * Any condition that, in the opinion of the investigator, would interfere with the evaluation of TBI-1301 or interpretation of subject safety or study results.

- * Known history of tuberculosis.

- * HIV positive.

- * Active HTLV or syphilis infection.

- * Active hepatitis B infection (hepatitis B surface antigen or HBV DNA positive).

- * Active hepatitis C infection (if hepatitis C antibody positive, HCV RNA positive).

- * Has no known active central nervous system metastases and/or carcinomatous meningitis.

- * Ongoing prior toxicities related to previous anti-cancer treatments (surgery, radiotherapy or adjuvant chemo-radiation) must be recovered to < grade 1 or baseline - * Pregnant women are excluded.

Gender: All

Minimum Age: 16 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

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Role: N/A

Affiliation: N/A

Overall Contact

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LOCATION