A Phase 1 study of subcutaneous toripalimab in recurrent or metastatic nasopharyngeal carcinoma.

AIMS: Considering the inconvenience brought by long-term administration of intravenous (IV) immune checkpoint inhibitors for cancer treatment, subcutaneous (SC) formulation needs to be explored. METHODS: This dose-finding Phase 1 study (NCT05751486) investigated SC toripalimab in patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC). In the initial dose-exploration cohorts, patients received SC toripalimab 240 mg Q3W or 480 mg Q6W, followed by a subsequent exploratory cohort receiving 360 mg Q3W, in combination with gemcitabine and cisplatin. The primary endpoint was pharmacokinetic profile of SC toripalimab. RESULTS: Between 24 November 2022 and 31 July 2023, 38 patients were enrolled (12, 13 and 13 patients received 240 mg Q3W, 360 mg Q3W and 480 mg Q6W SC toripalimab, respectively). As of the data cut-off date, the median follow-up was 17.2 months. SC toripalimab 360 mg Q3W provided similar serum trough concentration (Ctrough) and area under the curve (AUC) in Cycle 1 to the corresponding IV toripalimab 240 mg Q3W. SC toripalimab was well tolerated and exhibited a safety profile consistent with the established IV formulation. The objective response rates were 100% (95% CI 73.5, 100), 92.3% (95% CI 64.0, 99.8) and 92.3% (95% CI 64.0, 99.8) in the 240 mg Q3W, 360 mg Q3W and 480 mg Q6W cohorts, respectively. CONCLUSIONS: SC toripalimab showed consistent safety and antitumour activity with IV toripalimab for the first-line treatment of RM-NPC. Similar Ctrough and AUC values in cycle 1 of SC toripalimab 360 mg Q3W with IV toripalimab reference support further study.