A multi-center, open-label, randomized, parallel-controlled phase II study comparing pharmacokinetic, pharmacodynamics and safety of ripertamab (SCT400) to rituximab (MabThera®) in patients with CD20-positive B-cell non-Hodgkin lymphoma

Xiaohong Han; Mingzhi Zhang; Huaqing Wang; Qingyuan Zhang; Wei Li; Miaowang Hao; Yuhuan Gao; Jie Jin; Hanyun Ren; Yun Tang; Xiaonan Hong; Xiaoyan Ke; Hang Su; Lin Gui; Jianmin Luo; Liangzhi Xie; Wenlin Gai; Yuankai Shi

doi:10.21147/j.issn.1000-9604.2022.06.08

A multi-center, open-label, randomized, parallel-controlled phase II study comparing pharmacokinetic, pharmacodynamics and safety of ripertamab (SCT400) to rituximab (MabThera^®) in patients with CD20-positive B-cell non-Hodgkin lymphoma

Chin J Cancer Res. 2022 Dec 30;34(6):601-611. doi: 10.21147/j.issn.1000-9604.2022.06.08.

Authors

Xiaohong Han¹, Mingzhi Zhang², Huaqing Wang³, Qingyuan Zhang⁴, Wei Li⁵, Miaowang Hao⁶, Yuhuan Gao⁷, Jie Jin⁸, Hanyun Ren⁹, Yun Tang¹⁰, Xiaonan Hong¹¹, Xiaoyan Ke¹², Hang Su¹³, Lin Gui¹⁴, Jianmin Luo¹⁵, Liangzhi Xie¹⁶, Wenlin Gai¹⁶, Yuankai Shi¹⁴

Affiliations

¹ Clinical Pharmacology Research Center, Peking Union Medical College Hospital, State Key Laboratory of Complex Severe and Rare Diseases, NMPA Key Laboratory for Clinical Research and Evaluation of Drug, Beijing Key Laboratory of Clinical PK & PD Investigation for Innovative Drugs, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, China.
² Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.
³ Department of Medical Oncology, Tianjin People's Hospital, Tianjin 300121, China.
⁴ Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China.
⁵ Oncology Department of Cancer Center, the First Hospital of Jilin University, Changchun 130021, China.
⁶ Department of Hematology, Tangdu Hospital, Air Force Medical University, Xi'an 710038, China.
⁷ Department of Hematology, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
⁸ Department of Hematology, the First Affiliated Hospital of Zhejiang University, Hangzhou 310003, China.
⁹ Department of Hematology, Peking University First Hospital, Beijing 100034, China.
¹⁰ Department of Hematology, West China Hospital, Sichuan University, Chengdu 610041, China.
¹¹ Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
¹² Department of Hematology, Peking University Third Hospital, Beijing 100191, China.
¹³ Department of Lymphoma, the Fifth Medical Center of PLA General Hospital, Beijing 100071, China.
¹⁴ Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, Beijing 100021, China.
¹⁵ Department of Hematology, the Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
¹⁶ Beijing Engineering Research Center of Protein and Antibody, Sinocelltech Ltd., Beijing 100176, China.

PMID: 36714342
PMCID: PMC9829503
DOI: 10.21147/j.issn.1000-9604.2022.06.08

Abstract

Objective: This multi-center, open-label, randomized, parallel-controlled phase II study aimed to compare the pharmacokinetics (PK), pharmacodynamics (PD) and safety profile of ripertamab (SCT400), a recombinant anti-CD20 monoclonal antibody, to rituximab (MabThera^®) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL).

Methods: Patients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab (375 mg/m²) or rituximab (MabThera^®, 375 mg/m²). PK was evaluated using area under the concentration-time curve (AUC) from time 0 to d 85 (AUC_{0-85 d}), AUC from time 0 to week 1 (AUC_{0-1 w}), AUC from time 0 to week 2 (AUC_{0-2 w}), AUC from time 0 to week 3 (AUC_{0-3 w}), AUC from time 0 to week 8 (AUC_{0-8 w}), maximum serum concentration (C_max), terminal half-life (T_1/2), time to maximum serum concentration (T_max) and clearance (CL). Bioequivalence was confirmed if the 90% confidence interval (90% CI) of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%. PD, immunogenicity, and safety were also evaluated.

Results: From December 30, 2014 to November 24, 2015, a total of 84 patients were randomized (ripertamab, n=42; rituximab, n=42) and the PK analysis was performed on 76 patients (ripertamab, n=38; rituximab, n=38). The geometric mean ratios of ripertamab/rituximab for AUC_{0-85 d}, AUC_0-inf, and C_max were 96.1% (90% CI: 87.6%-105.5%), 95.9% (90% CI: 86.5%-106.4%) and 97.4% (90% CI: 91.6%-103.6%), respectively. All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%. For PD and safety evaluation, there was no statistical difference in peripheral CD19-positive B-cell counts and CD20-positive B-cell counts at each visit, and no difference in the incidence of anti-drug antibodies was observed between the two groups. The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.

Conclusions: In this study, the PK, PD, immunogenicity, and safety profile of ripertamab (SCT400) were similar to rituximab (MabThera^®) in Chinese patients with CD20-positive B-cell NHL.

Keywords: Anti-CD20 monoclonal antibody; non-Hodgkin lymphoma; pharmacokinetics; ripertamab; rituximab; safety.