Safety, Efficacy and Biomarker Analysis of Toripalimab in Patients with Previously Treated Advanced Urothelial Carcinoma: Results from a Multicenter Phase II Trial POLARIS-03.

Immunotherapy offers a second-line option for patients with metastatic urothelial carcinoma (mUC) who failed standard therapy, but the biomarkers for predicting response remain to be explored. This study aims to evaluate the safety, efficacy, and correlative biomarker of toripalimab in patients with previously treated mUC.

Patients with mUC received toripalimab 3 mg/kg Q2W. Clinical response was assessed every 8 weeks by an independent review committee per RECIST v1.1. Tumor PD-L1 expression, tumor mutational burden (TMB), and other biomarkers were evaluated.

Among the intention-to-treat population (n = 151), 85% of the patients experienced treatment-related adverse event (TRAE) and 20% experienced grade 3 and above TRAE. The objective response rate (ORR) was 26% with a disease control rate (DCR) of 45%. The median duration of response, progression-free survival (PFS) and overall survival (OS) were 19.7 months (95% CI: 13.9 to NE), 2.3 months (95% CI: 1.8 to 3.6) and 14.4 months (95% CI: 9.3 to 23.1), respectively. Both PD-L1+ and TMB-high (10 mutations/Mb as the cut off) patients had better ORR than PD-L1- patients (42% versus 17%, p = 0.002) and TMB low patients (48% versus 22%, p = 0.014), respectively. The TMB-high group also showed better PFS (12.9 versus 1.8 months, p < 0.001) and OS (not reached versus 10.0 months, p = 0.018) than the TMB-low group.

Toripalimab has demonstrated encouraging clinical activity in the second-line treatment of mUC with a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.

Clinical cancer research : an official journal of the American Association for Cancer Research. 2021 Nov 05 [Epub ahead of print]

Xinan Sheng, Haige Chen, Bin Hu, Xudong Yao, Ziling Liu, Xin Yao, Hongqian Guo, Yi Hu, Zhigang Ji, Hong Luo, Benkang Shi, Jiyan Liu, Jin Wu, FangJian Zhou, Zhisong He, Jinhai Fan, Weifeng Wang, Hui Feng, Sheng Yao, Patricia Keegan, Yiran Huang, Jun Guo

Department of Genitourinary Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute., Department of Urology, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine., Department of Urological Surgery, Liaoning Cancer Hospital & Institute., Department of Urology, Fudan University Shanghai Cancer Center., Oncology, Jilin University., Genitourinary Oncology, Tianjin Medical University Cancer Institute and Hospital., Nanjing Drum Tower Hospital, Nanjing University Medical School., PLA General Hospital Cancer Center Key Lab, PLA General Hospital., Urology, Peking Union Medical College Hospital., Chongqing Cancer Hospital., Urology, Qilu Hospital of Shandong University., Department of Biotherapy, West China Hospital of Sichuan University., Harbin Medical University Cancer Hospital., Department of Urology, Sun Yat-sen University Cancer Center., Peking University First Hospital., First Affiliated Hospital of Xi'an Jiaotong University., OrigiMed., Shanghai Junshi Biosciences Co., LTD., n/a, Shanghai Junshi Bioscience Co., Ltd., Clinical, TopAlliance Biosciences, Inc., Rockville, Maryland, USA., Urology, Renji Hospital, Shanghai Jiao Tong University School of Medicine., Department of Renal cancer and Melanoma, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute .

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