Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma

Lin Gui; Xiaohong Han; Xiaohui He; Yuanyuan Song; Jiarui Yao; Jianliang Yang; Peng Liu; Yan Qin; Shuxiang Zhang; Weijing Zhang; Wenlin Gai; Liangzhi Xie; Yuankai Shi

doi:10.21147/j.issn.1000-9604.2016.02.07

Phase I study of chimeric anti-CD20 monoclonal antibody in Chinese patients with CD20-positive non-Hodgkin's lymphoma

Chin J Cancer Res. 2016 Apr;28(2):197-208. doi: 10.21147/j.issn.1000-9604.2016.02.07.

Authors

Affiliations

¹ Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China;
² Department of Lymphoma, the 307th Hospital of Chinese People's Liberation Army & the Affiliated Hospital of Military Medical Sciences, Beijing 100071, China;
³ Cell Culture Research and Development Center, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100176, China.

PMID: 27199517
PMCID: PMC4865612
DOI: 10.21147/j.issn.1000-9604.2016.02.07

Abstract

Objective: This study was designed to determine the safety, pharmacokinetics and biologic effects of a human-mouse chimeric anti-CD20 monoclonal antibody (SCT400) in Chinese patients with CD20-positive B-cell non-Hodgkin's lymphoma (CD20(+) B-cell NHL). SCT400 has an identical amino acid sequence as rituximab, with the exception of one amino acid in the CH1 domain of the heavy chain, which is common in Asians.

Methods: Fifteen patients with CD20(+) B-cell NHL received dose-escalating SCT400 infusions (250 mg/m(2): n=3; 375 mg/m(2): n=9; 500 mg/m(2): n=3) once weekly for 4 consecutive weeks with a 24-week follow-up period. The data of all patients were collected for pharmacokinetics and pharmacodynamics analyses.

Results: No dose-limiting toxicities were observed. Most drug-related adverse events were grade 1 or 2. Two patients had grade 3 or 4 neutropenia. Under premedication, the drug-related infusion reaction was mild. A rapid, profound and durable depletion of circulating B cells was observed in all dose groups without significant effects on T cell count, natural killer (NK) cell count or immunoglobulin levels. No patient developed anti-SCT400 antibodies during the course of the study. SCT400 serum half-life (T1/2), maximum concentration (Cmax) and area under the curve (AUC) generally increased between the first and fourth infusions (P<0.05). At the 375 mg/m(2) dose, the T1/2 was 122.5±46.7 h vs. 197.0±75.0 h, respectively, and the Cmax was 200.6±20.2 g/mL vs. 339.1±71.0 g/mL, respectively. From 250 mg/m(2) to 500 mg/m(2), the Cmax and AUC increased significantly in a dose-dependent manner (P<0.05). Patients with a high tumor burden had markedly lower serum SCT400 concentrations compared with those without or with a low tumor burden. Of the 9 assessable patients, 1 achieved complete response and 2 achieved partial responses.

Conclusions: SCT400 is well-tolerated and has encouraging preliminary efficacy in Chinese patients with CD20(+) B-cell NHL.

Keywords: Chimeric anti-CD20 monoclonal antibody; non-Hodgkin's lymphoma; phase I study.

Grants and funding

This work was supported in part by Chinese National Major Project for New Drug Innovation (2008ZX09312-020, 2009ZX09503-014, 2012ZX09303012 and 2013ZX09402301), National Key Technology Support Program (2014BAI09B12), Beijing Municipal Science and Technology Commission Major Project for New Drug Innovation (Z111102071011001) and Beijing Municipal Science and Technology Commission Project for Beijing Key Laboratory (Z121102009212055).