Investigator Initiated Phase 1 Study of TBI-1301

Multi-center, Investigator Initiated Phase 1 Study of NY-ESO-1 Specific TCR Gene Transferred T Lymphocytes With Solid Tumors

Following pre-treatment with cyclophosphamide and/or fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to the patients with NY-ESO-1-expressing solid tumors.

Following pre-treatment with cyclophosphamide alone or in combination with fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to HLA-A*02:01 or HLA-A*02:06 positive patients with solid tumors which are 1) unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc), and 2) NY-ESO-1-expressing. The primary objective is to evaluate the safety and in vivo kinetics, and the secondary is to evaluate clinical effect.

Inclusion Criteria:

1. Histologically or cytologically confirmed solid tumors

2. Solid tumor, which is unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc)

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

4. NY-ESO-1-expression by PCR or immunohistochemistry

5. ECOG Performance Status, 0 or 1

6. Age >=20 years on consent

7. No treatment (surgery, chemotherapy, radiotherapy, etc.) and expected sufficient recovery from the treatment at the time of the lymphocytes collection for gene transfer.

8. Life expectancy >=16 weeks after consent

9. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria:

   • WBC >= 2,500/μL
   • Hemoglobin >= 8.0g/dL
   • Platelets >= 75,000/μL
   • T. bilirubin < 1.5 x ULN
   • AST(GOT), ALT(GPT) < 3.0 x ULN
   • Creatinine < 1.5 x ULN

10. Ability to understand the study contents and to give a written consent at his/her free will.

Exclusion Criteria:

1. The following serious complications are excluded from the study;

   • Unstable angina, cardiac infarction, or heart failure
   • Uncontrolled diabetes or hypertension
   • Active infection
   • Obvious interstitial pneumonia or lung fibrosis by chest X-ray
   • Active autoimmune disease requiring steroids or immunosuppressive therapy.

2. Serious hypersensitivity

3. Tumor cell invasion into CNS

4. Active multiple cancer

5. Positive for HBs antigen or HBV-DNA observed in serum

6. Positive for HCV antibody and HCV-RNA observed in serum

7. Positive for antibodies against HIV or HTLV-1

8. Left Ventricular Ejection Fraction (LVEF): <= 50％

9. Percutaneous Oxygen saturation: < 94％

10. History of serious hypersensitivity reactions to bovine or murine derived substances.

11. History of hypersensitivity reaction to drugs used in this study.

12. Psychological disorder or drug dependency which may have impact on the consent.

13. Pregnant females, lactating females (except when they cease and don't resume lactation) or female and male patients who cannot agree to practice the adequate birth control after the consent during the study

14. Clinically significant systemic illness that in the judgment of the PI or sub-investigator would compromise the patient's ability to tolerate protocol therapy or significantly increase the risk of complications.