The target populations for this phase I study with TBI-1301 are patients with advanced solid tumors. Patients' tumors will be required to express NY-ESO-1, which include but is not limited to ovarian cancer, synovial sarcoma, esophageal cancer and malignant melanoma. Patients must be positive for HLA-A*02:01 or HLA-A*02:06 and the patient's tumor tissue must be positive for NY-ESO-1 antigen expression. The study will take the subject's T cells, which are a natural type of immune cell in the blood, and send them to a laboratory to be modified. The changed T cells used in this study will be the subject's own T cells that have been genetically changed with the aim of attacking and destroying cancer cells. The manufacturing of T cells takes about 1 month to complete. The T cells will be given back to the subject through an intravenous infusion. The purpose of this study is to test the safety of genetically changed T cells and find out what effects, if any, they have in subjects with advanced solid tumors. The purpose of this study is to evaluate the safety profile of TBI-1301, to determine the recommended phase 2 (RP2D) dose of TBI-1301 when administered following cyclophosphamide pre-treatment and to evaluate evidence of efficacy of TBI-1301 using RECIST v1.1.
|Overal Status||Start Date||Phase||Study Type|
|Recruiting||Start Date: September 2016||Phase 1||Interventional|
Primary Outcome 1 - Measure: Safety profile (i.e. adverse events, presence/absence of RCR, analysis of clonality and PK of TBI-1301) assessed by CTCAE v.4.0 and laboratory testings.
Primary Outcome 1 - Time Frame: 8 weeks
Primary Outcome 2 - Measure: Recommended phase 2 (RP2D) dose o TBI-1301 when administered following cyclophosphamide pre-treatment
Primary Outcome 2 - Time Frame: 8 weeks
- Histologically or cytologically confirmed metastatic or recurrent unresectable solid
- 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 of PBMC
- If approved and funded standard therapy is available, subjects must have failed, be
intolerant to, be ineligible for, or have refused treatment.
- 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. See Section 11 for the evaluation of measurable disease.
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 ≥18 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 x109/L (1500/μL)
- WBC ≥ 2,500/μl
- Lymphocytes ≥ 500/μl
- Hemoglobin ≥ 80 g/L
- Platelets ≥ 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)
- Consent must be appropriately obtained in accordance with applicable local and
- 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.
- 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
- History of primary immunodeficiency.
- History of organ transplant that requires use of immunosuppressives.
- Known allergy to streptomycin sulfate or amphotericin B.
- 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).
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No