Safety, anti-tumour activity, and pharmacokinetics of fixed-dose SHR-1210, an anti-PD-1 antibody in advanced solid tumours: a dose-escalation, phase 1 study
Hongnan Mo, Jing Huang, Jiachen Xu, Xuelian Chen, Dawei Wu, Dong Qu, Xi Wang, Bo Lan, Xingyuan Wang, Jianping Xu, Honggang Zhang, Yihebali Chi, Qing Yang, Binghe Xu, Hongnan Mo, Jing Huang, Jiachen Xu, Xuelian Chen, Dawei Wu, Dong Qu, Xi Wang, Bo Lan, Xingyuan Wang, Jianping Xu, Honggang Zhang, Yihebali Chi, Qing Yang, Binghe Xu
Abstract
Background: To assess the safety profile, pharmacokinetics, pharmacodynamics and preliminary antitumour activity of fixed-dose SHR-1210, a novel anti-PD-1 antibody, in advanced solid tumours.
Methods: A total of 36 patients with advanced solid tumours received intravenous SHR-1210 at 60 mg, 200 mg and 400 mg (4-week interval after first dose followed by a 2-week schedule) until disease progression or intolerable toxicity. The concentration of SHR-1210 was detected for pharmacokinetics, and receptor occupancy on circulating T lymphocytes was assessed for pharmacodynamics.
Results: No dose-limiting toxicities were observed. Maximum administered dose was not reached. Most adverse events were grade 1 or 2. Treatment-related severe adverse events were found in two patients. No treatment-related death was reported. Two complete responses (gastric cancer, bladder carcinoma) and seven partial responses were seen. In responders, the median follow-up time was 16.0 months (range 8.3-19.5), and the median duration of response was not reached (range 2.7-17.5+ months). The half-life of SHR-1210 was 2.94 d, 5.61 d and 11.0 d for 3 dose levels, respectively.
Conclusions: Our results demonstrated a promising antitumour activity and a manageable safety profile of SHR-1210, displayed an explicit PK evidence of the feasibility of fixed dose, and established the foundation for further exploration.
Conflict of interest statement
Q.Y. is a salaried employee of Jiangsu Hengrui Medicine Co. The remaining authors declare no competing interests.
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