Bevacizumab biosimilar LY01008 compared with bevacizumab (Avastin) as first-line treatment for Chinese patients with unresectable, metastatic, or recurrent non-squamous non-small-cell lung cancer: A multicenter, randomized, double-blinded, phase III trial

Yuankai Shi, Kaijian Lei, Yuming Jia, Bingqiang Ni, Zhiyong He, Minghong Bi, Xicheng Wang, Jianhua Shi, Ming Zhou, Qian Sun, Guolei Wang, Dongji Chen, Yongqian Shu, Lianke Liu, Zhongliang Guo, Yong Liu, Junquan Yang, Ke Wang, Ke Xiao, Lin Wu, Tienan Yi, Debin Sun, Mafei Kang, Tianjiang Ma, Yimin Mao, Jinsheng Shi, Tiegang Tang, Yan Wang, Puyuan Xing, Dongqing Lv, Wangjun Liao, Zhiguo Luo, Bin Wang, Xiaohong Wu, Xiaoli Zhu, Shuhua Han, Qisen Guo, Rongyu Liu, Zhiwei Lu, Jianyong Zhang, Jian Fang, Changlu Hu, Yinghua Ji, Guolong Liu, Hong Lu, Dedong Wu, Junhong Zhang, Shuyang Zhu, Zheng Liu, Wensheng Qiu, Feng Ye, Yan Yu, Yanqiu Zhao, Qinhong Zheng, Jun Chen, Zhanyu Pan, Yiping Zhang, Wenjuan Lian, Bo Jiang, Bo Qiu, Guojun Zhang, Hua Zhang, Yanju Chen, Yuan Chen, Hongbing Duan, Manxiang Li, Shengming Liu, Lijun Ma, Hongming Pan, Xia Yuan, Xueli Yuan, Yulong Zheng, Emei Gao, Li Zhao, Shumin Wang, Can Wu, Yuankai Shi, Kaijian Lei, Yuming Jia, Bingqiang Ni, Zhiyong He, Minghong Bi, Xicheng Wang, Jianhua Shi, Ming Zhou, Qian Sun, Guolei Wang, Dongji Chen, Yongqian Shu, Lianke Liu, Zhongliang Guo, Yong Liu, Junquan Yang, Ke Wang, Ke Xiao, Lin Wu, Tienan Yi, Debin Sun, Mafei Kang, Tianjiang Ma, Yimin Mao, Jinsheng Shi, Tiegang Tang, Yan Wang, Puyuan Xing, Dongqing Lv, Wangjun Liao, Zhiguo Luo, Bin Wang, Xiaohong Wu, Xiaoli Zhu, Shuhua Han, Qisen Guo, Rongyu Liu, Zhiwei Lu, Jianyong Zhang, Jian Fang, Changlu Hu, Yinghua Ji, Guolong Liu, Hong Lu, Dedong Wu, Junhong Zhang, Shuyang Zhu, Zheng Liu, Wensheng Qiu, Feng Ye, Yan Yu, Yanqiu Zhao, Qinhong Zheng, Jun Chen, Zhanyu Pan, Yiping Zhang, Wenjuan Lian, Bo Jiang, Bo Qiu, Guojun Zhang, Hua Zhang, Yanju Chen, Yuan Chen, Hongbing Duan, Manxiang Li, Shengming Liu, Lijun Ma, Hongming Pan, Xia Yuan, Xueli Yuan, Yulong Zheng, Emei Gao, Li Zhao, Shumin Wang, Can Wu

Abstract

Background: Previous studies have demonstrated the preclinical pharmacological and toxicological consistency, and clinical pharmacokinetic equivalence of bevacizumab biosimilar LY01008 with reference bevacizumab (Avastin). This randomized controlled trial aimed to compare the efficacy and safety of LY01008 with Avastin in first-line treatment of Chinese patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC).

Methods: Stage IIIB-IV NSCLC patients with evaluable lesions, good physical status, and adequate organ functions from 67 centers across China were randomized in a ratio of 1:1 to receive LY01008 or Avastin 15 mg/kg intravenously in combination with paclitaxel/carboplatin (combined treatment) for 4-6 cycles, followed by maintenance monotherapy with LY01008 until disease progression, intolerable toxicity, or death. The primary endpoint was objective response rate (ORR) in accordance with Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 confirmed by independent radiological review committees (IRRC). Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety. This study was registered in ClinicalTrials.gov (NCT03533127).

Results: Between December 15th , 2017, and May 15th , 2019, a total of 649 patients were randomized to the LY01008 (n = 324) or Avastin (n = 325) group. As of September 25th , 2019 for primary endpoint analysis, 589 patients received ORR evaluation, with a median number of combined treatment cycles of 5 (range 1-6) and median duration of treatment of 3.0 (range 0.0-5.1) months. ORR of response-evaluable patients in the LY01008 and Avastin groups were 48.5% and 53.0%, respectively. The stratified ORR ratio was 0.91 (90% CI 0.80-1.04, within the prespecified equivalence margin of 0.75-1.33). Up to May 15th , 2020, with a median follow-up of 13.6 (range 0.8-28.4) months, no notable differences in DCR, median DoR, median PFS, median OS, and 1-year OS rate were observed between the LY01008 and Avastin groups. There were no clinically meaningful differences in safety and immunogenicity across treatment groups.

Conclusions: LY01008 demonstrated similarity to Avastin in terms of efficacy and safety in Chinese patients with advanced or recurrent non-squamous NSCLC. LY01008 combined with paclitaxel/carboplatin is expected to become a new treatment option for unresectable, metastatic, or recurrent non-squamous NSCLC patients in the first-line setting.

Keywords: LY01008; anti-VEGF monoclonal antibody; anti-angiogenesis; avastin; bevacizumab; biosimilar; non-small cell lung cancer; vascular endothelial growth factor.

Conflict of interest statement

The tested drug LY01008 in this study is the product of Luye Pharma Group Ltd., which provided main funding to this study. Emei Gao, Li Zhao, Shumin Wang, and Can Wu are employees of the Clinical Research Center of Luye Pharma Group Ltd., Luye Life Sciences Group, Beijing, China. All other authors declare that they have no conflict of interests.

© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.

Figures

FIGURE 1
FIGURE 1
Flowchart of participants’ disposition. Abbreviations: ITT, intention‐to‐treat; ORR, objective response rate; FAS, full analysis set; PPS, per‐protocol set
FIGURE 2
FIGURE 2
Forest plot for subgroup analysis of objective response rate in the full analysis set. Abbreviations: CI: confidence interval; ECOG: Eastern Cooperative Oncology Group; PS: performance status; EGFR, epidermal growth factor receptor
FIGURE 3
FIGURE 3
Kaplan‐Meier curves of the LY01008 group and the Avastin group in the full analysis set. A: Percentage rate of patients with a duration of response; B: Progression‐free survival; C: Overall survival. Abbreviations: CI, confidence interval; mDoR, median duration of response; mPFS, median progression‐free survival; mOS, median overall survival; NR, not reached

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