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

NCT02869217 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: 1301-02
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Lung Cancer; Bladder Cancer; Liver Cancer; Synovial Sarcoma; Melanoma; Esophageal Cancer; Ovarian Cancer; NY-ESO-1 Expressing Solid Tumors in HLA-A2 Positive Patients

Keywords

NY-ESO-1 expressing solid tumors in HLA-A2 positive patients

Outcome Measures

Primary Outcomes (2)

• 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.

  8 weeks

• Recommended phase 2 (RP2D) dose o TBI-1301 when administered following cyclophosphamide and fludarabine pre-treatment

  8 weeks

Secondary Outcomes (1)

• Evidence of efficacy (i.e. anti-tumor effect) of TBI-1301 measured using RECIST v1.1

  8 weeks

Study Arms (2)

Cohort B (retreatment)

EXPERIMENTAL

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

Cohort C (double infusion)

EXPERIMENTAL

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

Interventions

Cyclophosphamide DRUG

Cohort B (retreatment); Cohort C (double infusion)

TBI-1301 BIOLOGICAL

Cohort B (retreatment); Cohort C (double infusion)

Fludarabine DRUG

Cohort B (retreatment); Cohort C (double infusion)

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Health Network, Toronto: lead
• Takara Bio Inc.: collaborator

Study Sites (1)

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

MeSH Terms

Conditions

Sarcoma, Synovial; Melanoma; Esophageal Neoplasms; Ovarian Neoplasms; Lung Neoplasms; Urinary Bladder Neoplasms; Liver Neoplasms

Interventions

Cyclophosphamide; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Urologic Neoplasms; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Liver Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 9, 2016
• First Posted: August 16, 2016
• Study Start: September 1, 2016
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

CA (1)