Investigator Initiated Phase 1 Study of TBI-1301

Phase 1

• Conditions: Solid Tumors
• Interventions: Drug: TBI-1301; Drug: Cyclophosphamide; Drug: Fludarabine

• Registration Number: NCT02366546
• Lead Sponsor: Mie University

Brief Summary

Following pre-treatment with cyclophosphamide and/or fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to the patients with NY-ESO-1-expressing solid tumors.

Detailed Description

Following pre-treatment with cyclophosphamide alone or in combination with fludarabine, NY-ESO-1-specific TCR gene transduced T lymphocytes are transferred to HLA-A\*02:01 or HLA-A\*02:06 positive patients with solid tumors which are 1) unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc), and 2) NY-ESO-1-expressing. The primary objective is to evaluate the safety and in vivo kinetics, and the secondary is to evaluate clinical effect.

Study Timeline

• Study First Submitted: 2015-02-12
• Study First Submitted QC: 2015-02-18
• Study First Posted: 2015-02-19
• Study Start: 2015-03
• Primary Completion: 2018-09
• Status Verified: 2018-10
• Last Update Submitted: 2018-10-22
• Last Update Posted: 2018-10-24

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 9

Inclusion Criteria

1. Histologically or cytologically confirmed solid tumors

2. Solid tumor, which is unresectable, refractory to standard therapy (chemotherapy, radiotherapy, etc)

3. HLA-A*02:01 or HLA-A*02:06 positive

4. NY-ESO-1-expression by PCR or immunohistochemistry

5. ECOG Performance Status, 0 or 1

6. Age >=20 years on consent

7. No treatment (surgery, chemotherapy, radiotherapy, etc.) and expected sufficient recovery from the treatment at the time of the lymphocytes collection for gene transfer.

8. Life expectancy >=16 weeks after consent

9. No severe damage on the major organs (bone marrow, heart, lung, liver, kidney, etc) and meet the following lab value criteria:

   • WBC >= 2,500/μL
   • Hemoglobin >= 8.0g/dL
   • Platelets >= 75,000/μL
   • T. bilirubin < 1.5 x ULN
   • AST(GOT), ALT(GPT) < 3.0 x ULN
   • Creatinine < 1.5 x ULN

10. Ability to understand the study contents and to give a written consent at his/her free will.

Exclusion Criteria

1. The following serious complications 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. Serious hypersensitivity

3. Tumor cell invasion into CNS

4. Active multiple cancer

5. Positive for HBs antigen or HBV-DNA observed in serum

6. Positive for HCV antibody and HCV-RNA observed in serum

7. Positive for antibodies against HIV or HTLV-1

8. Left Ventricular Ejection Fraction (LVEF): <= 50％

9. Percutaneous Oxygen saturation: < 94％

10. History of serious hypersensitivity reactions to bovine or murine derived substances.

11. History of hypersensitivity reaction to drugs used in this study.

12. Psychological disorder or drug dependency which may have impact on the consent.

13. Pregnant females, lactating females (except when they cease and don't resume lactation) or female and male patients who cannot agree to practice the adequate birth control after the consent during the study

14. 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: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Low dose TBI-1301 with pre-treatment 1	TBI-1301	TBI-1301(5\*10\^8) single-dose administration with pre-treatment of cyclophosphamide alone.
Low dose TBI-1301 with pre-treatment 1	Cyclophosphamide	TBI-1301(5\*10\^8) single-dose administration with pre-treatment of cyclophosphamide alone.
High dose TBI-1301 with pre-treatment 1	TBI-1301	TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide alone.
High dose TBI-1301 with pre-treatment 1	Cyclophosphamide	TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide alone.
High dose TBI-1301 with pre-treatment 2	TBI-1301	TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
High dose TBI-1301 with pre-treatment 2	Cyclophosphamide	TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
High dose TBI-1301 with pre-treatment 2	Fludarabine	TBI-1301(5\*10\^9) single-dose administration with pre-treatment of cyclophosphamide and fludarabine.
TBI-1301 with pre-treatment 1 or 2	Cyclophosphamide	Arm1, 2 or 3, which is considered as optimal.
TBI-1301 with pre-treatment 1 or 2	Fludarabine	Arm1, 2 or 3, which is considered as optimal.
TBI-1301 with pre-treatment 1 or 2	TBI-1301	Arm1, 2 or 3, which is considered as optimal.

Primary Outcome Measures

Name	Time	Method
Appearance of replication competent retrovirus by PCR	4 weeks	Confirm no replication competent retrovirus observed.
Incidence and grade of adverse events (CTCAE)	4 weeks	• Confirm the toxicity profile, which is measured by the degree of grade and seriousness, duration, causality, classification, etc. of the adverse events.
Appearance of clonality by LAM-PCR	4 weeks	Confirm no clonality is observed.
Kinetics of TBI-1301 in blood by realtime-PCR	8 weeks	Evaluate persistence and expansion of transferred TBI-1301.

Trial Locations

Locations (1)

Mie University Hospital; 🇯🇵 Tsu, Mie, Japan