Results from phase I/II study of NY-ESO-1-specific TCR gene-transduced T cell therapy (TBI-1301, mipetresgene autoleucel) in patients with advanced synovial sarcoma.

person Akira Kawai Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan info_outline 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, Akihiko Matsumine, Shinichi Kageyama, Takafumi Ueda

Authors person Akira Kawai Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan info_outline 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, Akihiko Matsumine, Shinichi Kageyama, Takafumi Ueda Organizations Department of Musculoskeletal Oncology, National Cancer Center Hospital, Tokyo, Japan, Cancer Center, Mie University Hospital, Tsu-Shi, OH, Japan, Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, Tsu, Japan, Department of Advanced Medical Development, The Cancer Institute Hospital of JFCR, Tokyo, Japan, Department of Medical Oncology, Sapporo Medical University School of Medicine, Sapporo, Japan, Department of Orthopedic Surgery, Sapporo Medical University School of Medicine, Sapporo, Japan, Department of Hematology, Oncology and Cardiovascular Medicine, Kyushu University Hospital, Fukuoka-Shi Higashi-Ku, Japan, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan, Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka-Shi, Japan, Osaka International Cancer Institute, Osaka-Shi Chuo-Ku, Japan, Department of Pathology, Institute of Medical Science, Tokyo Medical University, Tokyo, Japan, Department of Personalized Cancer Immunotherapy, Mie University Graduate School of Medicine, Tsu, Japan, Takara Bio Inc., Kusatsu, Japan, Department of Orthopaedic Surgery, University of Fukui, Fukui, Japan, Suzuka Kaisei Hospital, Suzuka, Japan, Kodama Hospital, Takarazuka, Japan Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Takara Bio Inc. Background: Synovial sarcoma is one of malignant soft tissue tumors with a poor prognosis. A cancer-testis antigen NY-ESO-1 is expressed in the tumors of 50-80% synovial sarcoma patients. The purpose of this study was to evaluate the safety and the efficacy of gene engineered autologous T cell product with NY-ESO-1 siTCR retroviral vector which expressed affinity-enhanced NY-ESO-1-specific TCR and siRNA to silence endogenous TCR (TBI-1301). Methods: This was an open label phase I/II study to evaluate safety, appearance of replication competent retrovirus (RCR), appearance of clonality, in vivo cell kinetics and clinical responses. TBI-1301 were manufactured from each subject’s leucocytes stimulated with anti-CD3 antibody and Retronectin and transduced with NY-ESO-1 siTCR retroviral vector. TBI-1301 was infused at split dose of 5 x 10 9 cells following cyclophosphamide treatment at 750 mg/m 2 for two days to HLA-A*02:01 or HLA-A*02:06 positive subjects with synovial sarcoma expressing NY-ESO-1, which were surgically unresectable and refractory to anthracycline therapy. Results: Eight subjects were enrolled and treated with TBI-1301. The objective response rate was 50.0% with best overall partial response in 4 of 8 subjects according to RECIST v1.1/irRECIST and the median overall survival was 650 days. Cytokine release syndrome (CRS) occurred in 50.0% (4/8) and consisted of 1 subject with grade 1 CRS and 3 subjects with grade 2 CRS. All subjects who developed CRS recovered with prespecified treatment, in which 2 subjects were treated with symptomatic therapy, 1 subject was treated with tocilizumab and 1 subject was treated with both tocilizumab and corticosteroid. No subjects had immune effector cell- associated neurotoxicity syndrome (ICANS). RCR and clonal dominance were not detected in any subjects throughout the study period. Conclusions: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumors will become a promising treatment for advanced or recurrent synovial sarcoma with acceptable toxicity. Clinical trial information: NCT03250325.

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