Safety, Efficacy and Biomarker Analysis of Toripalimab in previously treated advanced melanoma: results of the POLARIS-01 multicenter phase II trial.

Purpose: In contrast to the predominant chronic UV exposure-induced cutaneous melanoma in Caucasians, acral and mucosal comprise the majority of melanomas in Asia and respond less effectively to established treatments. The clinical application of PD-1 blockade is yet to be explored in metastatic melanoma in China. Patients and Methods: This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese patients with melanoma who had failed in systemic treatments. Toripalimab was given at 3 mg/kg i.v. once every 2 weeks until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate. Results: 128 Patients with melanoma were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23 months after the last enrollment, 116 (90.6%) experienced treatment-related adverse events. >= Grade 3 TRAEs occurred in 25 (19.5%) patients. Among 127 patients assessed, 1 complete response, 21 partial response, and 51 stable disease were observed for objective response rate of 17.3% and disease control rate of 57.5%. Median duration of response was not reached. Median progression-free survival was 3.6 months [95% confidence interval (CI) 2.7-5.3] and median overall survival was 22.2 months (95% CI, 15.3-NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% vs. 11.9%, P = 0.0065), PFS (7.7 months vs. 2.7 months, P = 0.013), and OS (not reached vs. 14.4 months, P = 0.0005) than PD-L1-negative patients. Conclusions: This is the largest prospective anti-PD-1 clinical study in advanced melanoma with predominantly acral and mucosal subtypes. Toripalimab demonstrated a manageable safety profile and durable clinical response in Chinese patients with metastatic melanoma refractory to standard therapy.