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
Authors: Shi Yuankai , Lei Kaijian , Jia Yuming , Ni Bingqiang , He Zhiyong , Bi Minghong , Wang Xicheng , Shi Jianhua , Zhou Ming , Sun Qian , Wang Guolei , Chen Dongji , Shu Yongqian , Liu Lianke , Guo Zhongliang , Liu Yong , Yang Junquan , Wang Ke , Xiao Ke , Wu Lin , Yi Tienan , Sun Debin , Kang Mafei , Ma Tianjiang , Mao Yimin , Shi Jinsheng , Tang Tiegang , Wang Yan , Xing Puyuan , Lv Dongqing , Liao Wangjun , Luo Zhiguo , Wang Bin , Wu Xiaohong , Zhu Xiaoli , Han Shuhua , Guo Qisen , Liu Rongyu , Lu Zhiwei , Zhang Jianyong , Fang Jian , Hu Changlu , Ji Yinghua , Liu Guolong , Lu Hong , Wu Dedong , Zhang Junhong , Zhu Shuyang , Liu Zheng , Qiu Wensheng , Ye Feng , Yu Yan , Zhao Yanqiu , Zheng Qinhong , Chen Jun , Pan Zhanyu , Zhang Yiping , Lian Wenjuan , Jiang Bo , Qiu Bo , Zhang Guojun , Zhang Hua , Chen Yanju , Chen Yuan , Duan Hongbing , Li Manxiang , Liu Shengming , Ma Lijun , Pan Hongming , Yuan Xia , Yuan Xueli , Zheng Yulong , Gao Emei , Zhao Li , Wang Shumin , Wu Can 
Published: June 2021

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.