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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02869217
Recruitment Status : Active, not recruiting
First Posted : August 16, 2016
Last Update Posted : December 8, 2023
Takara Bio Inc.
Information provided by (Responsible Party):
University Health Network, Toronto

Brief Summary:

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, lung cancer, bladder cancer, liver 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 and fludarabine pre-treatment, to evaluate the safety of repeat dosing of TBI-1301, to assess the presence/absence of RCR appearance after TBI-1301 infusion, to assess the presence or absence of clonality by LAM-PCR, and to evaluate evidence of efficacy of TBI-1301 using RECIST v1.1.

Condition or disease Intervention/treatment Phase
NY-ESO-1 Expressing Solid Tumors in HLA-A2 Positive Patients Synovial Sarcoma Melanoma Esophageal Cancer Ovarian Cancer Lung Cancer Bladder Cancer Liver Cancer Drug: Cyclophosphamide Biological: TBI-1301 Drug: Fludarabine Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 22 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase Ib Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors
Study Start Date : September 2016
Estimated Primary Completion Date : September 2024
Estimated Study Completion Date : September 2024

Arm Intervention/treatment
Experimental: Cohort B (retreatment)

Cyclophosphamide will be given intravenously (by vein) at a fixed dose of 750mg/m^2/d for 2 days.

Fludarabine will be given intravenously at a fixed dose of 30mg/m^2/d for 2 days.

TBI-1301 cells will be infused on Day 0 at a dose of 5x10^9 cells.

*Patients will only enter into this cohort if they have already been enrolled in another cohort prior

Drug: Cyclophosphamide
Biological: TBI-1301
Drug: Fludarabine
Experimental: Cohort C (double infusion)

Cyclophosphamide will be given intravenously (by vein) at a fixed dose of 750mg/m^2/d for 2 days.

Fludarabine will be given intravenously at a fixed dose of 30mg/m^2/d for 2 days.

TBI-1301 cells will be infused on Day 0 and Day 14 at a dose of 5x10^9 cells.

Drug: Cyclophosphamide
Biological: TBI-1301
Drug: Fludarabine

Primary Outcome Measures :
  1. 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 ]
  2. Recommended phase 2 (RP2D) dose o TBI-1301 when administered following cyclophosphamide and fludarabine pre-treatment [ Time Frame: 8 weeks ]

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   16 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02869217

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Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
University Health Network, Toronto
Takara Bio Inc.
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Responsible Party: University Health Network, Toronto Identifier: NCT02869217    
Other Study ID Numbers: 1301-02
First Posted: August 16, 2016    Key Record Dates
Last Update Posted: December 8, 2023
Last Verified: December 2023
Keywords provided by University Health Network, Toronto:
NY-ESO-1 expressing solid tumors in HLA-A2 positive patients
Additional relevant MeSH terms:
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Sarcoma, Synovial
Neoplasms by Histologic Type
Neoplasms, Connective and Soft Tissue
Neoplasms, Connective Tissue
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists