EBV-TCR-T（YT-E001）for Patients With EBV-positive Recurrent or Metastatic NPC

Nasopharyngeal Carcinoma Clinical Trial

Official title: A Pilot Study of EBV-TCR-T(YT-E001) in NPC Patients

Status Recruiting

Clinical Trial 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. These and lots of clinical 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.

Nasopharyngeal carcinoma (NPC), a kinds of head-neck malignant tumor, which used to appear mostly in southern China (especially in Fujian and Guangdong and Guangxi provinces). Most patients with NPC show evidence of infection with the Epstein Barr virus (EBV) before or at the time of their diagnosis. EBV is found in the cancer cells of almost all patients with advanced stage NPC, and play a role in causing and inducing the disease program and development. The cancer cells infected by EBV are able to hide from the body's immune system and escape destruction. We want to see if EBV antigen special T cells (YT-E001) could recognize and kill special parts of EBV infected cells, and finally inhibit the tumor recurrence or metastasis of NPC patients.

This study will focus on the NPC highly expressed EBV antigen such as LMP1, LMP2 and EBNA1，the high affinity TCR target the above EBV antigen were screened from the healthy donor using the sorting and single cell cloning technique. Then, using the lentivirus to transduce the TCR gene to the autologous T cells.

This study will investigate the safety and tolerability of EBV-TCR-T cell therapy in subjects with NPC who had received prior therapy for their disease but their disease has progressed or relapsed.

The chemotherapy we will use for lymphodepletion is a combination of cyclophosphamide and fludarabine. Cyclophosphamide and fludarabine are the chemotherapy agents most commonly used for lymphodepletion in immunotherapy clinical trials.

Clinical Trial Description

This Phase I/II study is designed as single dose pilot trial evaluating the safety and of EBV-TCR-TT cell therapy in subjects with NPC 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- A02:01/24:02/11:01, and EBV serum positive. Subjects will receive cytoreductive chemotherapy with cyclophosphamide and fludarabine on days -6 and -4 followed by infusion of dose of about 2×108 EBV-TCR-T(YT-E001).

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 every 8 weeks until progression of their disease or the end or termination of trial. ;

Related Conditions & MeSH terms

• Nasopharyngeal Carcinoma

• NCT number: NCT03648697
• Study type: Interventional
• Source: Fujian Cancer Hospital
• Contact: JianJi Pan
• Phone: 0591-83660063
• Email: panjianji@126.com
• Status: Recruiting
• Phase: Phase 2
• Start date: October 10, 2018
• Completion date: October 10, 2021