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 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 gene and siRNAs to inhibit the expression of endogenous T-cell receptors (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 x 109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I part) and efficacy-related (objective response rate [ORR] by RECIST v1.1/irRECIST; phase II part). 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%CI: 15.7-84.3) with best overall partial response in 4 of 8 patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and 7 of 8 patients (87.5%) had adverse drug reactions but no deaths were attributed to adverse events. Cytokine release syndrome occurred in 4 of 8 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 synovial sarcoma with acceptable toxicity.

• Authors: Akira Kawai, Mikiya Ishihara, Tomoki Nakamura, Shigehisa Kitano, Shintaro Iwata, Kohichi Takada, Makoto Emori, Koji Kato, Makoto Endo, Yoshihiro Matsumoto, Shigeki Kakunaga, Eiichi Sato, Yoshihiro Miyahara, Kunihiko Morino, Shinya Tanaka, Shuichi Takahashi, Fujio Matsuo, Akihiko Matsumine, Shinichi Kageyama, Takafumi Ueda
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) (Oct 04 2023) ISSN: 1557-3265 [Electronic] United States
• PMID: 37792433 (Publication Type: Journal Article)