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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.

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.

SUBMITTER: Mo H

PROVIDER: S-EPMC6162236 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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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.

Mo Hongnan H Huang Jing J Xu Jiachen J Chen Xuelian X Wu Dawei D Qu Dong D Wang Xi X Lan Bo B Wang Xingyuan X Xu Jianping J Zhang Honggang H Chi Yihebali Y Yang Qing Q Xu Binghe B

British journal of cancer 20180514 5

<h4>Background</h4>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.<h4>Methods</h4>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 pharmacokineti ...[more]

PMID: 29755117

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Dataset Information

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.

Publications

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.

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