Recombinant humanized anti-PD-1 monoclonal antibody toripalimab in patients with metastatic urothelial carcinoma: Preliminary results of an open-label phase II clinical study.

4554 Background: Patients with advanced metastatic urothelial carcinoma (UC) who experience disease progression after standard therapy have limited treatment options. Phase I studies of toripalimab in subjects with heavily pretreated metastatic UC have demonstrated an acceptable safety profile and promising clinical activity. Here we report the preliminary safety and efficacy result of toripalimab in a phase II clinical study in Chinese patients with refractory/metastatic urothelial carcinoma. (Clinical trial ID: NCT03113266). Methods: Metastatic UC Patients will receive toripalimab, also known as JS001, 3 mg/kg Q2W until disease progression or unacceptable toxicity. All patients with measurable disease will be assessed for clinical response every 8 weeks according to RECISTv1.1. Tumor PD-L1 expression and tumor mutational burden will be measured for correlation with clinical response. Results: From May 2017 to February 10, 2019, 79 patients were enrolled from 7 participating centers. The median age was 61 years with 57.5% male. By the cut-off date of Jan 20, 2019, common treatment related AEs were mostly grade 1 or 2, including anemia, hyperglycemia, ALT increased, AST increased and hypothyroidism. Among 65 evaluable patients, 2 complete responses, 18 partial responses, and 13 stable diseases were observed, for an objective response rate (ORR) of 30.8% and a disease control rate of 50.8%. 70% (14/20) responses were ongoing by the cut-off date. PD-L1 expression results were obtained from 56 subjects. PD-L1+ patients (n=16, 28.6%) had significant better ORR than PD-L1- patients (n=40), 62.5% versus 15.0% ( p<0.01). Conclusions: Toripalimab has demonstrated encouraging clinical activity in chemo-refractory UC patients and a manageable safety profile. Toripalimab elicited a favorable 62.5% ORR in PD-L1 positive patients, while PD-L1 negative patients also achieved a 15% ORR, including one complete response. Patients will be continuously monitored for additional safety and efficacy readouts (DOR, PFS and OS). Clinical trial information: NCT03113266.