A phase 3 study of rituximab biosimilar HLX01 in patients with diffuse large B-cell lymphoma

Yuankai Shi, Yongping Song, Yan Qin, Qingyuan Zhang, Xiaohong Han, Xiaonan Hong, Dong Wang, Wei Li, Yang Zhang, Jifeng Feng, Jianmin Yang, Huilai Zhang, Chuan Jin, Yu Yang, Jianda Hu, Zhao Wang, Zhengming Jin, Hang Su, Huaqing Wang, Haiyan Yang, Weijun Fu, Mingzhi Zhang, Xiaohong Zhang, Yun Chen, Xiaoyan Ke, Li Liu, Ding Yu, Guo'an Chen, Xiuli Wang, Jie Jin, Tao Sun, Xin Du, Ying Cheng, Pingyong Yi, Xielan Zhao, Chaoming Ma, Jiancheng Cheng, Katherine Chai, Alvin Luk, Eugene Liu, Xin Zhang, Yuankai Shi, Yongping Song, Yan Qin, Qingyuan Zhang, Xiaohong Han, Xiaonan Hong, Dong Wang, Wei Li, Yang Zhang, Jifeng Feng, Jianmin Yang, Huilai Zhang, Chuan Jin, Yu Yang, Jianda Hu, Zhao Wang, Zhengming Jin, Hang Su, Huaqing Wang, Haiyan Yang, Weijun Fu, Mingzhi Zhang, Xiaohong Zhang, Yun Chen, Xiaoyan Ke, Li Liu, Ding Yu, Guo'an Chen, Xiuli Wang, Jie Jin, Tao Sun, Xin Du, Ying Cheng, Pingyong Yi, Xielan Zhao, Chaoming Ma, Jiancheng Cheng, Katherine Chai, Alvin Luk, Eugene Liu, Xin Zhang

Abstract

Rituximab in combination with chemotherapy has shown efficacy in patients with diffuse large B-cell lymphoma (DLBCL) for more than 15 years. HLX01 was developed as the rituximab biosimilar following a stepwise approach to demonstrate biosimilarity in analytical, pre-clinical, and clinical investigations to reference rituximab. With demonstrated pharmacokinetic similarity, a phase 3 multi-center, randomized, parallel, double-blind study (HLX01-NHL03) was subsequently conducted to compare efficacy and safety between HLX01 plus cyclophosphamide, doxorubicin, vincristine, and prednisone (H-CHOP) and reference rituximab plus CHOP (R-CHOP) in a total of 407 treatment-naïve, CD20-positive DLBCL patients aged 18-80 years. The primary efficacy endpoint was best overall response rate (ORR) within six cycles of treatment in the per-protocol set (PPS). Secondary endpoints included 1-year efficacy outcomes, safety, and immunogenicity profile. The results showed difference in ORRs [H-CHOP 94.1%; R-CHOP 92.8%] between two treatment groups was 1.4% (95% confidence interval [CI], - 3.59 to 6.32, p = 0.608) which falls within the pre-defined equivalence margin of ± 12%. The safety profile was comparable between the treatment groups, with a similar overall incidence of treatment-emergent adverse events (H-CHOP 99.5%, R-CHOP 99.0%, p = 1.000) and serious adverse events (H-CHOP 34.0%, R-CHOP 32.5%, p = 0.752). This study established bioequivalence in efficacy and safety between HLX01 and reference rituximab. The trial was registered at http://www.chinadrugtrials.org.cn on 26 August 2015 [#CTR20150583].

Keywords: DLBCL; Efficacy equivalence; Rituximab biosimilar.

Conflict of interest statement

CMM, JCC, KC, AL, EL, and XZ are employees of Shanghai Henlius Biotech, Inc. All other authors declare no competing interests.

Figures

Fig. 1
Fig. 1
a Patient disposition of all screened patients. b Baseline patient demographics and disease status of full analysis dataset (FAS)

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Source: PubMed

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