Abstract CT113: A dose-exploring, randomized, open-label, Phase I study for toripalimab subcutaneous injection in patients with advanced nasopharyngeal carcinoma
Authors: Mai Hai-Qiang , Han Ya-Qian , Wu Guo-Wu , Yang Kun-Yu , Chen Chuan-Ben , Wang Mo , Luo Xian-Ming , Wei Shuang-Hui , Tan Xi , Xue Peng , Xu Rui-Hua 
Published: April 2024

Abstract
Background Toripalimab, a humanized IgG4K monoclonal antibody specific for PD-1, in combination with gemcitabine and cisplatin (GP) has been approved as a first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) by the US FDA in October 2023. This is the first-in-human clinical trial (NCT05751486) to investigate the pharmacokinetics of toripalimab subcutaneous (SC) formulation in RM-NPC and determine the appropriate subcutaneous administration regimen for subsequent clinical trials.
Methods Patients with histologically confirmed RM-NPC and without previously systemic therapy for RM disease were enrolled. Eligible patients were assigned to receive toripalimab SC 240 mg every 3 weeks (Q3W), 360 mg Q3W or 480 mg Q6W, in combination with GP for up to 6 cycles, followed by toripalimab SC monotherapy until disease progression, intolerable toxicity, or completion of 2 years of treatment. Tumor response was assessed per RECIST v1.1. The primary endpoint was pharmacokinetic (PK) profile. Secondary endpoints included safety, efficacy, and immunogenicity.
Results From November 24, 2022 to November 20, 2023, a total of 38 patients (240 mg cohort, n=12; 360 mg cohort, n=13; 480 mg cohort, n=13) were enrolled, the median follow-up time was 6.8 months. The median age was 49 years, and 28 (73.7%) patients were males. PK analysis showed that in the first cycle, the exposure (AUC0-21days and Ctrough) of toripalimab 360 mg Q3W SC regimen was comparable to that of 240 mg Q3W intravenous (IV) regimen (table 1). Objective Response Rates (ORR) in 240 mg, 360 mg and 480 mg cohorts were 100%, 92.3% and 92.3%, respectively. By November 20, 2023, 71.1% (27/38) patients have ongoing responses. No new safety signal was identified. The incidence of Grade ≥3 adverse events (AEs) was 76.3% with no fatal AEs. The incidence of investigator-determined immune-related AEs was 36.8% with 1 (2.6%) Grade ≥3.
Conclusions Toripalimab SC formulation showed similar safety and clinical efficacy with toripalimab IV formulation when combined with GP in patients with RM-NPC. The exposure of toripalimab 360 mg Q3W SC was comparable to that of 240 mg Q3W IV. Toripalimab SC formulation is planned for phase III clinical development.

Table 1. PK parameters of each dose cohort. Parameters JS001sc Cohorts (N = 36) IV ref-model based 240 mg SC Q3W, n=12 480 mg SC Q6W, n=12 360 mg SC Q3W, n=12 240 mg IV Q3W, n=1014 Cycle 1 Ctrough, μg/mL GM (% CV) 10.2 (57.1) 8.4 (43.5) 18.6 (50.1) 10.2 (61.8) Cycle 1 AUC (0-Xd), μg•d/mL GM (% CV) 8376 (0-21 d) (39.3) 25316 (0-42 d) (35.4) 14229 (0-21 d) (58.2) 13386 (27.0) Bioavailability 62.6% (25.3%-100.0%)
Citation Format: Hai-Qiang Mai, Ya-Qian Han, Guo-Wu Wu, Kun-Yu Yang, Chuan-Ben Chen, Mo Wang, Xian-Ming Luo, Shuang-Hui Wei, Xi Tan, Peng Xue, Rui-Hua Xu. A dose-exploring, randomized, open-label, Phase I study for toripalimab subcutaneous injection in patients with advanced nasopharyngeal carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr CT113.