Open AccessA phase I study of toripalimab, an anti‐PD‐1 antibody, in patients with refractory malignant solid tumors
Author(s) -
Wei XiaoLi,
Ren Chao,
Wang FengHua,
Zhang Yang,
Zhao HongYun,
Zou BenYan,
Wang ZhiQiang,
Qiu MiaoZhen,
Zhang DongSheng,
Luo HuiYan,
Wang Feng,
Yao Sheng,
Xu RuiHua
Publication year - 2020
Publication title -
cancer communications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.119
H-Index - 53
ISSN - 2523-3548
DOI - 10.1002/cac2.12068
Subject(s) - medicine , pharmacodynamics , pharmacokinetics , rash , adverse effect , refractory (planetary science) , toxicity , gastroenterology , cancer , pharmacology , physics , astrobiology
Background Several programmed cell death ligand 1 (PD‐L1)/programmed cell death protein 1 (PD‐1) antibodies have been approved for cancer treatment worldwide. Their pharmacokinetic and pharmacodynamic characteristics have been reported mainly in western countries, but related data in Chinese patients are limited. This study was conducted to investigate the safety, efficacy, pharmacokinetics, and pharmacodynamics of an anti‐PD‐1 antibody, toripalimab, in Chinese patients. Methods A single‐center phase I study was conducted in Sun Yat‐sen University Cancer Center. Eligible patients were adults with histologically confirmed, treatment‐refractory, advanced, solitary malignant tumors. Toripalimab was intravenously infused every 2 weeks in dose‐escalating cohorts at 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg. The study followed standard 3 + 3 design. Results Between 15 th March 2016 and 27 th September 2016, 25 patients were enrolled, of whom 3 (12.0%), 7 (28.0%), 6 (24.0%), 6 (24.0%), 3 (12.0%) received 0.3 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg, and 240 mg toripalimab, respectively. After a median follow‐up time of 5.0 months (range: 1.5‐19.8 months), we observed that the commonest treatment‐related adverse events (TRAEs) were fatigue (64.0%) and rash (24.0%). No grade 3 or higher TRAEs were observed. No dose‐limiting toxicity, treatment‐related serious adverse events (SAEs), or treatment‐related death occurred. Objective response rate was 12.5%. The half‐life of toripalimab was 150‐222 h after a single dose infusion. Most patients, including those from the 0.3 mg/kg group, maintained complete PD‐1 receptor occupancy (> 80%) on activated T cells since receiving the first dose of toripalimab. Conclusions Toripalimab is a promising anti‐PD‐1 antibody, which was well tolerated and demonstrated anti‐tumor activity in treatment‐refractory advanced solitary malignant tumors. Further exploration in various tumors and combination therapies is warranted.