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

Phase 1

Completed

• Conditions: Synovial Sarcoma
• Interventions: Biological: TBI-1301; Drug: Cyclophosphamide

• Registration Number: NCT03250325
• Lead Sponsor: Takara Bio Inc.

Brief Summary

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.

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 Timeline

• Study First Submitted: 2017-08-08
• Study First Submitted QC: 2017-08-10
• Study First Posted: 2017-08-15
• Study Start: 2017-09-20
• Primary Completion: 2020-01-23
• Study Completion: 2022-03-09
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-18
• Last Update Posted: 2024-11-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Split dose of 5x10^9 TBI-1301	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.
Split dose of 5x10^9 TBI-1301	Cyclophosphamide	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.

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (5)

National Hospital Organization Osaka National Hospital; 🇯🇵 Osaka, Japan

Mie University Hospital; 🇯🇵 Tsu, Mie, Japan

National Cancer Center Hospital; 🇯🇵 Chuo-ku, Tokyo, Japan

Sapporo Medical University Hospital; 🇯🇵 Sapporo, Hokkaido, Japan

Kyushu University Hospital; 🇯🇵 Fukuoka, Japan