Efficacy and safety of MIL60 compared with bevacizumab in advanced or recurrent non-squamous non-small cell lung cancer: a phase 3 randomized, double-blind study

Rui Wan, Xiaorong Dong, Qun Chen, Yan Yu, Shujun Yang, Xiaochun Zhang, Guojun Zhang, Yueyin Pan, Sanyuan Sun, Chengzhi Zhou, Wei Hong, Hui Zhao, Lei Yang, Linian Huang, Rong Wu, Aimin Zang, Rui Ma, Lin Wu, Dongqing Lv, Xiuhua Fu, Jianguo Han, Wenxin Li, Jianchun Duan, Kai Wang, Ou Jiang, Yinglan Chen, Zhongliang Guo, Hongjun Gao, Juyi Wen, Shubin Wang, Enfeng Zhao, Gaofeng Li, Lu Yue, Li Liang, Aiping Zeng, Xiaoshan Wang, Yuxi Zhu, Hongming Pan, Zhaoxia Dai, Weineng Feng, Guofang Zhao, Chuan Lin, Chong Li, Na Li, Yangyi Bao, Yinyin Li, Yanjun Su, Min Zhao, Haohui Fang, Yulong Zhu, Yu Zhang, Lieming Ding, Yang Wang, Xiaobin Yuan, Jie Wang, Rui Wan, Xiaorong Dong, Qun Chen, Yan Yu, Shujun Yang, Xiaochun Zhang, Guojun Zhang, Yueyin Pan, Sanyuan Sun, Chengzhi Zhou, Wei Hong, Hui Zhao, Lei Yang, Linian Huang, Rong Wu, Aimin Zang, Rui Ma, Lin Wu, Dongqing Lv, Xiuhua Fu, Jianguo Han, Wenxin Li, Jianchun Duan, Kai Wang, Ou Jiang, Yinglan Chen, Zhongliang Guo, Hongjun Gao, Juyi Wen, Shubin Wang, Enfeng Zhao, Gaofeng Li, Lu Yue, Li Liang, Aiping Zeng, Xiaoshan Wang, Yuxi Zhu, Hongming Pan, Zhaoxia Dai, Weineng Feng, Guofang Zhao, Chuan Lin, Chong Li, Na Li, Yangyi Bao, Yinyin Li, Yanjun Su, Min Zhao, Haohui Fang, Yulong Zhu, Yu Zhang, Lieming Ding, Yang Wang, Xiaobin Yuan, Jie Wang

Abstract

Background: We compared the efficacy, safety, and immunogenicity of MIL60 with reference bevacizumab as first-line treatment in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC) in this phase 3, randomized, double-blind study.

Methods: Patients with untreated advanced or recurrent NSCLC were randomized (1:1 ratio) to receive either MIL60 or bevacizumab in combination with paclitaxel/carboplatin. Patients with non-progressive disease continued maintenance single-agent MIL60 until disease progression, or intolerable toxicity. The primary endpoint was the 12-week objective response rates (ORR12) by independent review committee (IRC) using RECIST 1.1. Bioequivalence was established if the ORR ratio located between 0.75 and 1/0.75. The trial was registered with clinicaltrials.gov (NCT03196986).

Findings: Between Aug 23, 2017, and May 8, 2019, 517 patients were randomly assigned to MIL60 group (n=257) and bevacizumab group (n=260). In the full analysis set (FAS) population including all randomized and evaluable patients who received at least one dose of MIL60 or bevacizumab, the ORR12 in MIL60 group and bevacizumab group were 48.6% and 43.1%, respectively. The ORR ratio of these two groups were 1.14 (90% CI 0.97-1.33), which fell within the pre-specified equivalence boundaries (0.75-1/0.75). The median DOR was 5.7 months (95% CI 4.5-6.2) for MIL60 and 5.6 months (95% CI 4.3-6.4) for bevacizumab. No significant difference was noted in median PFS (7.2 vs. 8.1 months; HR 1.01, 95% CI 0.78-1.30, p=0.9606) and OS (19.3 vs. 16.3 months; HR 0.81, 95% CI 0.64-1.02, p=0.0755). Safety and tolerability profiles were similar between the two groups. No patient detected positive for Anti-drug antibody (ADA).

Interpretation: The efficacy, safety and immunogenicity of MIL60 were similar with bevacizumab, providing an alternative treatment option for advanced or recurrent non-squamous NSCLC.

Funding: This study was sponsored by Betta Pharmaceutical Co., Ltd.

Keywords: MIL60; bevacizumab; biosimilar; equivalence; non-squamous NSCLC.

Conflict of interest statement

Lieming Ding, Yang Wang and Xiaobin Yuan are employees of Betta Pharmaceuticals, which provided funding for the study. Other authors declared no conflict of interests.

© 2021 The Authors.

Figures

Figure 1
Figure 1
Study flowchart
Figure 2
Figure 2
Waterfall plot of best percent change in target lesions from baseline in MIL60 arm (A) and bevacizumab (B), and subgroup analysis for tumor response (C). Data cutoff date was Aug 1, 2019.
Figure 3
Figure 3
Kaplan–Meier plot of duration of response (A), progression-free survival (B) and overall survival (C) in the MIL60 and reference bevacizumab groups as assessed by IRC. Data cutoff date was October 31, 2020.

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Source: PubMed

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