Brief Title: T Cell Receptor-transduced T Cells Targeting NY-ESO-1 for Treatment of Patients With NY-ESO-1- Expressing Malignancies

INTRODUCTION

• Org Study ID: 201504002
• Secondary ID: N/A
• NCT ID: NCT02457650
• Sponsor: Shenzhen Second People's Hospital

BRIEF SUMMARY

Background:

Autologous T cells engineered to express a T cell receptor (TCR) targeting NY-ESO-1 will be
infused back to patients with NY-ESO-1- expressing malignancies. The patients pretreated with
a lymphodepleting preconditioning regimen will be monitored after infusion of anti-NY-ESO-1
TCR-transduced T cells for adverse events, persistence of anti-NY-ESO-1 TCR-transduced T
cells and treatment efficacy.

Objectives:

To evaluate the safety and the efficacy of anti-NY-ESO-1 TCR-transduced T cell-based
immunotherapy for patients with NY-ESO-1- expressing malignancies.

Eligibility:

Patients older than one year of age, who have relapsed or refractory malignancies that
express both NY-ESO-1 and human leukocyte antigen (HLA)-A2 molecules.

Patients must have adequate organ functions.

Design:

- Peripheral blood from patients will be collected for isolation of peripheral blood
mononuclear cells (PBMCs), which will be transduced with a lentiviral or retroviral
vector encoding an HLA-A2 restricted anti-NY-ESO-1 TCR gene.

- Patients will receive a lymphodepleting preconditioning regimen to prepare their immune
system to accept modified T cells.

- Patients will receive an infusion of their own modified T cells. They will remain in the
hospital to be monitored for adverse events until they have recovered from the
treatment.

- Patients will have frequent follow-up visits to monitor the persistence of modified T
cells and efficacy of the treatment.

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DETAILED DESCRIPTION

Despite advances has been made to date in the treatment of patients with hematologic
malignancies, clinical trials targeting solid cancers have achieved limited efficacy. One
important reason is due to lack of ideal cancer antigens. NY-ESO-1 is expressed in various
types of cancers, including neuroblastoma, hepatoma, myeloma, melanoma, esophagus, prostate,
bladder, breast and ovarian cancers. While, in normal somatic tissues, NY-ESO-1 expression is
restricted to the germline cells, which lack HLA molecules and cannot present peptides
derived from NY-ESO-1 for recognition by T cells. Therefore, NY-ESO-1 specific T cells will
only recognize and kill NY-ESO-1-expressing cancer cells, but not normal cells, thus avoiding
induction of autoimmune reaction. With these unique features, NY-ESO-1 has been selected as
an attractive tumor antigen candidate for cancer immunotherapy in various clinical trials.

In this trial, autologous T cells engineered to express a T cell receptor (TCR) targeting
NY-ESO-1 will be infused back to patients with NY-ESO-1- expressing malignancies after they
receive a lymphodepleting preconditioning regimen. The patients will be monitored after
infusion of anti-NY-ESO-1 TCR-transduced T cells for adverse events, persistence of
anti-NY-ESO-1 TCR-transduced T cells and treatment efficacy.

Primary objectives:

To determine the safety and feasibility of the administration of anti-NY-ESO-1 TCR transduced
T cells in patients with HLA-A2+ NY-ESO-1-expressing malignancies.

Secondary objectives:

To determine if the treatment can result in clinical regression of malignant tumors in the
patients.

To determine the in vivo persistency of the anti-NY-ESO-1 TCR-transduced T cells.

• Overall Status
  Recruiting
• Start Date
  
• Phase
  Phase 1
• Study Type
  Interventional