Safety, Efficacy and Biomarker Analysis of Toripalimab in previously treated advanced melanoma: results of the POLARIS-01 multicenter phase II trial
Mené en Chine sur 128 patients atteints d’un mélanome de stade avancé, cet essai de phase II évalue l’efficacité, du point de vue du taux de réponse objective, et la toxicité du toripalimab (un anti-PD-1) après l’échec de plusieurs lignes de traitements systémiques
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. Experimental Design: This phase II study was to evaluate safety and efficacy of toripalimab in advanced Chinese melanoma patients who had failed in systemic treatments. Toripalimab was given at 3 mg/kg IV Q2W until disease progression or unacceptable toxicity. The primary objective was safety and objective response rate. Results: 128 melanoma patients were enrolled, including 50 acral and 22 mucosal. As of August 15, 2019, 23-month 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 CR, 21 PR and 51 SD 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 3.6m (95%CI 2.7 to 5.3) and median overall survival was 22.2m (95%CI 15.3 to NE). Patients with positive PD-L1 staining in tumor biopsies had significant better ORR (38.5% versus 11.9%, p=0.0065), PFS (7.7m versus 2.7m, p=0.013) and OS (not reached versus 14.4m, 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.