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

• Register: ClinicalTrials.gov
• Last refreshed on: 19 December 2023
• Main ID: NCT02869217
• Date of registration: 09/08/2016
• Prospective Registration: Yes
• Primary sponsor: University Health Network, Toronto
• Public title: Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors
• Scientific title: Phase Ib Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors
• Date of first enrolment: September 2016
• Target sample size: 22
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT02869217
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1

Countries of recruitment

Canada

Key inclusion & exclusion criteria

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.



Age minimum: 16 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Bladder Cancer

NY-ESO-1 Expressing Solid Tumors in HLA-A2 Positive Patients

Synovial Sarcoma

Melanoma

Ovarian Cancer

Esophageal Cancer

Liver Cancer

Lung Cancer

Intervention(s)

Biological: TBI-1301

Drug: Fludarabine

Drug: Cyclophosphamide

Primary Outcome(s)

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. [Time Frame: 8 weeks]

Recommended phase 2 (RP2D) dose o TBI-1301 when administered following cyclophosphamide and fludarabine pre-treatment [Time Frame: 8 weeks]

Secondary Outcome(s)

Evidence of efficacy (i.e. anti-tumor effect) of TBI-1301 measured using RECIST v1.1 [Time Frame: 8 weeks]

Secondary ID(s)

1301-02

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Takara Bio Inc.