Safety and Efficacy of NY-ESO-1 Antigen-Specific T-Cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial

Abstract Purpose: To determine, for patients with advanced or recurrent synovial sarcoma (SS) not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor (TCR) gene and siRNA to inhibit the expression of endogenous TCR (product code: TBI-1301). Patients and Methods: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days −3 and −2 (induction period) followed by a single dose of 5×109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I) and efficacy-related [objective response rate (ORR) by RECIST v1.1/immune-related RECIST (irRECIST); phase II]. Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. Results: For the full analysis set (N = 8; phase I, n = 3; phase II, n = 5), the ORR was 50.0% (95% confidence interval, 15.7–84.3) with best overall partial response in four of eight patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and seven of eight patients (87.5%) had adverse drug reactions, but no deaths were attributed to adverse events. Cytokine release syndrome occurred in four of eight patients (50.0%), but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication-competent retrovirus, and lymphocyte clonality were absent. Conclusions: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1-positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent SS with acceptable toxicity.