Lung Cancer, Nonsmall Cell, Recurrent Clinical Trial
Official title:
Pilot Study of Affinity-enhanced Anti-NY-ESO-1 TCR Engineered Autologous T Cells in NSCLC Patients
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.
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.
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