Study of TBI-1301 (NY-ESO-1 T Cell Receptor Gene Transduced Autologous T Lymphocytes) in Patients with Synovial Sarcoma

Multi-center Phase I/II Study of NY-ESO-1 T Cell Receptor Gene Transferred T Lymphocytes in Patients with Synovial Sarcoma

The purpose of this study is to evaluate the safety and the efficacy of TBI-1301 for NY-ESO-1 expressing synovial sarcoma when administered following cyclophosphamide pre-treatment.

Study Overview

• Status: Completed
• Conditions: Synovial Sarcoma
• Intervention / Treatment: Biological: TBI-1301; Drug: Cyclophosphamide

Detailed Description

Following pre-treatment with cyclophosphamide, NY-ESO-1-specific T cell receptor (TCR) gene transduced T lymphocytes are transferred to human leukocyte antigen (HLA)-A*02:01 or HLA-A*02:06 positive patients with synovial sarcoma expressing NY-ESO-1, which are surgically unresectable and refractory to anthracycline therapy. The primary objective is to evaluate the safety in the phase 1 and the efficacy in the phase 2.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Osaka, Japan, 540-0006
    • National Hospital Organization Osaka National Hospital
  • Hokkaido
    • Sapporo, Hokkaido, Japan, 060-8543
      • Sapporo Medical University Hospital
  • Mie
    • Tsu, Mie, Japan, 514-8507
      • Mie University Hospital
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • National Cancer Center Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Histologically confirmed synovial sarcoma
2. Surgically unresectable tumor
3. Progressing or recurrent synovial sarcoma which has been treated with 1-4 regimens of systemic chemotherapies including anthracycline
4. HLA-A*02:01 or HLA-A*02:06 positive
5. Tumor that express NY-ESO-1 by immunohistochemistry
6. ≥ 18 years of age
7. Measurable lesions that are evaluable by the RECIST ver1.1
8. ECOG Performance Status of 0, 1 or 2
9. No treatment such as chemotherapy and be expected to recover fully from the previous treatment at the time of the lymphocytes collection for manufacturing
10. Life expectancy ≥ 16 weeks after consent
11. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria; Total bilirubin ≤ 1.5 x upper limit of normal (ULN); AST(GOT), ALT(GPT) < 3.0 x ULN; Creatinine < 1.5 x ULN; 2,500/μL < WBC ≤ULN; Hemoglobin ≥ 8.0g/dL; Platelets ≥ 75,000/μL
12. Patients must be able to understand the study contents and to give a written consent at his/her free will. Additionally, if patients are below 20 years of age, proxies must be able to give a written consent.

Exclusion Criteria:

1. Patients with the following conditions are excluded from the study; Unstable angina, cardiac infarction, or heart failure; Uncontrolled diabetes or hypertension; Active infection; Obvious interstitial pneumonia or lung fibrosis by chest X-ray; Active autoimmune disease requiring steroids or immunosuppressive therapy.
2. Active metastatic tumor cell invasion into CNS
3. Active multiple cancer
4. Positive for HBs antigen or HBV-DNA observed in serum
5. Positive for HCV antibody and HCV-RNA observed in serum
6. Positive for antibodies against HIV or HTLV-1
7. Left Ventricular Ejection Fraction (LVEF) ≤ 50%
8. History of serious hypersensitivity reactions to bovine or murine derived substances.
9. History of hypersensitivity reaction to ingredients or excipients of investigational drugs used in this study
10. History of hypersensitivity reaction to antibiotics used in manufacturing for the investigational drug used in this study.
11. Pregnant females, lactating females (except when they cease and do not resume lactation) or female and male patients who cannot agree to practice the adequate birth control from the consent to 6 months after infusion of the investigational drug.
12. Clinically significant systemic illness that in the judgment of the PI or sub-investigator would compromise the patient's ability to tolerate protocol therapy or significantly increase the risk of complications.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Split dose of 5x10^9 TBI-1301; Split dose of 5x10^9 TBI-1301 will be administered intravenously for 2 days following cyclophosphamide pre-treatment 750 mg/m2/d for 2 days.	Biological: TBI-1301; Split dose of TBI-1301 is administered intravenously for 2 days following cyclophosphamide pre-treatment.; Drug: Cyclophosphamide; Cyclophosphamide (750mg/m2/day x 2 days Intravenous (IV)) is administered as pre-treatment medication of TBI-1301.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Phase I) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values	Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.	52 weeks
(Phase I) Appearance of replication competent retrovirus (RCR) by PCR	Confirm that no replication competent retrovirus observed.	52 weeks
(Phase I) Appearance of clonality by linear amplification mediated (LAM)-PCR	Confirm that no clonality is observed.	52 weeks
(Phase I) Blood kinetics of TBI-1301 by realtime-PCR	Evaluate persistence and expansion of transferred TBI-1301.	52 weeks
(Phase II) Overall response rate	Evaluate response rate by measuring response using RECIST v1.1 and irRECIST	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
(Phase I) Objective response rate	Evaluate response rate by measuring response using RECIST v1.1 and irRECIST	52 weeks
(Phase I/II) Progression free rate	Evaluate progression free rate by measuring response using RECIST v1.1 and irRECIST	12 weeks
(Phase I/II) Progression free survival	Evaluate progression free survival	52 weeks
(Phase I/II) Overall survival	Evaluate overall survival	52 weeks
(Phase II) Adverse event, mortality, severe adverse event, discontinuation due to adverse event, laboratory test values	Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.	52 weeks
(Phase II) Appearance of RCR	Confirm that no replication competent retrovirus observed.	52 weeks
(Phase II) Appearance of clonality (LAM-PCR)	Confirm that no clonality is observed.	52 weeks
(Phase II) Blood kinetics of TBI-1301 by realtime-PCR	Evaluate persistence and expansion of transferred TBI-1301.	52 weeks

Collaborators and Investigators

• Sponsor: Takara Bio Inc.
• Investigators: Study Director: Masanobu Kimura, Takara Bio Inc.

Study record dates

Study Major Dates

• Study Start (Actual): September 20, 2017
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): March 9, 2022

Study Registration Dates

• First Submitted: August 8, 2017
• First Submitted That Met QC Criteria: August 10, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Actual): November 20, 2024
• Last Update Submitted That Met QC Criteria: November 18, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; Cell therapy; NY-ESO-1; Synovial sarcoma; Adoptive cell transfer; T cell receptor gene therapy
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Connective and Soft Tissue; Neoplasms, Connective Tissue; Sarcoma; Sarcoma, Synovial; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Cyclophosphamide
• Other Study ID Numbers: 1301-03

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No