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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02869217
Recruitment Status : Recruiting
First Posted : August 16, 2016
Last Update Posted : September 28, 2018
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 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.

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 Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
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 : June 2019
Estimated Study Completion Date : June 2020

Arm Intervention/treatment
Experimental: Dose Level -1, Dose Level 1, RP2D (expansion)
Cyclophosphamide will be given intravenously (by vein) at a fixed dose of 750mg/m2/d for 2 days
Drug: Cyclophosphamide
Biological: TBI-1301

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 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

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Ages Eligible for Study:   18 Years and older   (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 of PBMC harvest.
  • 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 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.
  • 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).
  • 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).

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

Contact: Marcus Butler, MD 416-946-4521

Canada, Ontario
Princess Margaret Cancer Centre Recruiting
Toronto, Ontario, Canada, M5G 2M9
Contact: Marcus Butler, M.D.    416-946-4521   
Principal Investigator: Marcus Butler, M.D.         
Sponsors and Collaborators
University Health Network, Toronto
Takara Bio Inc.

Responsible Party: University Health Network, Toronto Identifier: NCT02869217     History of Changes
Other Study ID Numbers: 1301-02
First Posted: August 16, 2016    Key Record Dates
Last Update Posted: September 28, 2018
Last Verified: September 2018

Keywords provided by University Health Network, Toronto:
NY-ESO-1 expressing solid tumors in HLA-A2 positive patients

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Esophageal Neoplasms
Liver Neoplasms
Sarcoma, Synovial
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
Gastrointestinal Neoplasms
Digestive System Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Liver Diseases
Neoplasms, Connective Tissue
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents