A phase I study of toripalimab, an anti-PD-1 antibody, in patients with refractory malignant solid tumors.

Abstract

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 15th March 2016 and 27th 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.

• Authors: Xiao-Li Wei, Chao Ren, Feng-Hua Wang, Yang Zhang, Hong-Yun Zhao, Ben-Yan Zou, Zhi-Qiang Wang, Miao-Zhen Qiu, Dong-Sheng Zhang, Hui-Yan Luo, Feng Wang, Sheng Yao, Rui-Hua Xu
• Journal: Cancer communications (London, England) (Cancer Commun (Lond)) Vol. 40 Issue 8 Pg. 345-354 (08 2020) ISSN: 2523-3548 [Electronic] United States
• PMID: 32589350 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.

Chemical References

• Antibodies, Monoclonal, Humanized
• PDCD1 protein, human
• Programmed Cell Death 1 Receptor
• toripalimab

Topics

• Adenocarcinoma (drug therapy)
• Adult
• Antibodies, Monoclonal, Humanized (therapeutic use)
• Bile Duct Neoplasms (drug therapy)
• Carcinoma, Squamous Cell (drug therapy)
• Esophageal Neoplasms (drug therapy)
• Esophageal Squamous Cell Carcinoma (drug therapy)
• Female
• Humans
• Male
• Melanoma (drug therapy)
• Nasopharyngeal Neoplasms (drug therapy)
• Pancreatic Neoplasms (drug therapy)
• Pharyngeal Neoplasms (drug therapy)
• Programmed Cell Death 1 Receptor (antagonists & inhibitors)
• Stomach Neoplasms (drug therapy)
• Tongue Neoplasms (drug therapy)