NCT03029273

NY-ESO-1 TCR （TAEST16001）for Patients With Advanced NSCLC

Pilot Study of Affinity-enhanced Anti-NY-ESO-1 TCR Engineered Autologous T Cells in NSCLC Patients

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 20 (estimated)
• Sponsor: Guangzhou Institute of Respiratory Disease · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

TCR-T cell therapy experienced a breakthrough for treating tumors in recent years. Phase I / II trial of NY-ESO-1-specific TCR-T treatment for synovial sarcoma and melanoma conducted by the Rosenberg team at the National Cancer Institute showed that 61% Synovial cell sarcoma and 55% melanoma had therapeutic responses. Another report of a phase I / II clinical trial for multiple myeloma showed that 20 patients received high affinity anti-NY-ESO-1 and LAGE-1 specific TCR-T treatment, 16 of them (80%) had the average progression-free survival of 19.1 months with minor side effect. These achievements indicate that TCR-T cell therapy can target a variety of tumors including solid tumors without any severe side effects found in CAR-T trials. This study is mainly focused on tumor testis antigen (Cancer-Testis Antigen), because it is not expressed in normal cells. NY-ESO-1 antigen is commonly expressed in 10-50% of melanoma, lung, liver, esophageal, breast, prostate, bladder, thyroid and ovarian cancer cases, 60% of multiple myeloma cases, and 70-80% of synovial cell sarcoma. Approximately 700,000 new cases of lung cancer are identified each year in China, 70% of them die within one to two years after diagnosis due to the lack of effective treatment. To address that unmet needs, our TCR-T treatment targets non-small cell lung cancer with NY-ESO-1 antigen expression. This study will investigate the safety and tolerability of TAEST16001 (TAEST: TCR Affinity Enhancing Specific T cell Therapy, autologous T cells transduced with affinity enhanced NY-ESO-1 TCR) cell therapy in subjects with NSCLC who have received prior therapy for their disease but their disease has progressed or relapsed.

Detailed description

This Phase 1 study is designed as a cell dose escalation trial evaluating the safety of TAEST16001 T cell therapy in subjects with NSCLC who have received prior therapy for their disease but the disease has progressed or relapsed. Anti-tumor activity and other exploratory objectives will be assessed. Subjects enter from a Screening Protocol and are positive for HLA-A2\*02:01 and have tumor that express NY-ESO-1. The subjects will be evaluated DLT and MTD using a modified 3+3 cell dose escalation design to determine the cell dose range. Subjects will receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) on day -7 to day -5 followed by infusion of dose of about 5×109 TAEST16001 and IL-2(s.c.). Subjects will stay in hospital for safety and efficacy assessment daily from T cell infusion (Day 0) through Day 7, and then weekly until week 4 and then at 8 weeks, 12 weeks, 16 weeks and every 3 months until progression of their disease.

Conditions

• Lung Cancer, Nonsmall Cell, Recurrent

Interventions

Type	Name	Description
DRUG	Cyclophosphamide and Fludarabine	Seven days prior to infusion of TCR-T cell, subjects receive cytoreductive chemotherapy with cyclophosphamide (250-500mg/m2/day) plus fludarabine (25mg/m2/day) for 3 days.
BIOLOGICAL	Anti-NY-ESO-1 TCR transduced T cells	A single dose of Anti-NY-ESO-1 TCR transduced T cells (about 5×109) will be intravenously (i.v.) administered Additionally, following infusion of Anti-NY-ESO-1 TCR transduced T cells, IL-2 subcutaneous injections (500,000 IU/day) will be administered for 14 days concomitantly to each subject.

Timeline

• Start date: 2017-03-21
• Primary completion: 2019-03-01
• Completion: 2019-03-01
• First posted: 2017-01-24
• Last updated: 2019-01-17

Locations

1 site across 1 country: China