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

Purpose: 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 and Methods: 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. Results: 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% confidence interval (CI): 13.9-not estimable], 2.3 months (95% CI, 1.8-3.6), and 14.4 months (95% CI, 9.3-23.1), respectively. Both PD-L1 and TMB-high (10 mutations/Mb as the cutoff) patients had better ORR than PD-L1_ patients (42% vs. 17%, P=0.002) and TMB-low patients (48% vs. 22%, P = 0.014), respectively. The TMB-high group also showed better PFS (12.9 vs. 1.8 months, P < 0.001) and OS (not reached versus 10.0 months, P=0.018) than the TMB-low group. Conclusions: Toripalimab has demonstrated encouraging clinical activity in the second-line treatment ofmUCwith a manageable safety profile. PD-L1 expression and TMB were two independent biomarkers in the study.