EClinicalMedicine (Dec 2021)
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
Affiliations
- Rui Wan
- State Key Laboratory of Molecular Oncology, 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, China
- Xiaorong Dong
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
- Qun Chen
- Medical Oncology, Fuzhou pulmonary Hospital of Fujian, Fuzhou, China
- Yan Yu
- Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
- Shujun Yang
- Department of Internal Medicine, Henan Cancer Hospital & Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, China
- Xiaochun Zhang
- Cancer Precision Medicine Center, The Affiliated Hospital of Qingdao University, Qingdao, China
- Guojun Zhang
- Respiratory Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
- Yueyin Pan
- Department of Oncology Chemotherapy, the First Affiliated Hospital of USTC (Anhui Provincial Hospital), Hefei, China
- Sanyuan Sun
- Oncology, Xuzhou Central Hospital, Xuzhou, China
- Chengzhi Zhou
- Pulonary and Critical Care Medicine, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
- Wei Hong
- Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China
- Hui Zhao
- Respiratory, The Second Hospital of Anhui Medical University, Hefei, China
- Lei Yang
- Department of Respiratory Oncology, Gansu Provincial Cancer Hospital, Lanzhou, China
- Linian Huang
- Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Rong Wu
- Department of Internal Oncology II, Shengjing Hospital of China Medical University, Liaoning, China
- Aimin Zang
- Internal Medicine-Oncology, Affiliated Hospital of Hebei, Baoding, China
- Rui Ma
- Medical Oncology Department of Thoracic Cancer (II), Liaoning Cancer Hospital & Institute, Shenyang, China
- Lin Wu
- Thoracic Medicine Department II, Hunan Cancer Hospital, Changsha, China
- Dongqing Lv
- Respiratory, Taizhou Hospital of Zhejiang Province, Taizhou, China
- Xiuhua Fu
- Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, China
- Jianguo Han
- Oncology, Chifeng Municipal Hospital, Chifeng, China
- Wenxin Li
- Oncology, Inner Mongolia People's Hospital, Hohhot, China
- Jianchun Duan
- State Key Laboratory of Molecular Oncology, 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, China
- Kai Wang
- Respiratory, The Second Affiliated Hospital Zhejiang University School of Medicine, Hangzhou, China
- Ou Jiang
- Department of Oncology, The Second People's Hospital of Neijiang, Neijiang, China
- Yinglan Chen
- Medical Oncology, Jiangxi Province Cancer Hospital, Nanchang, China
- Zhongliang Guo
- Department of Respiratory Medicine, Shanghai East Hospital, Shanghai, China
- Hongjun Gao
- Department of pulmonary oncology, The Fifth Medical Center of PLA General Hospital, Beijing, China
- Juyi Wen
- Department of Radiation Oncology, The Sixth Medical Center of PLA General Hospital, Beijing, China
- Shubin Wang
- Medical Oncology, Peking University Shenzhen Hospital, Shenzhen, China
- Enfeng Zhao
- Three and Four Departments of Radiotherapy and Chemotherapy, Cangzhou Hospital of Integrated Traditional Chinese and Western of Hebei Province, Cangzhou, China
- Gaofeng Li
- Thoracic surgery, Yunnan Cancer Hospital, Kunming, China
- Lu Yue
- Oncology, Qingdao Municipal Hospital, Qingdao, China
- Li Liang
- Oncology, Peking University Third Hospital, Beijing, China
- Aiping Zeng
- Department of Chemotherapy, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, China
- Xiaoshan Wang
- Oncology, Sichuan Provincial People's Hospital, Chengdu, China
- Yuxi Zhu
- Department of Oncology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Hongming Pan
- Oncology Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
- Zhaoxia Dai
- Department of Thoracic Medical Oncology II, The Second Hospital of Dalian Medical University, Dalian, China
- Weineng Feng
- Head and Neck/Thoracic Medical Oncology, The First People's Hospital of Foshan, Foshan, China
- Guofang Zhao
- Department of Cardiothoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No.2 Hospital), Ningbo, China
- Chuan Lin
- Oncology, Yibin Second People's Hospital, Yibin, China
- Chong Li
- Department of Respiratory Medicine, The First People's Hospital of Changzhou, Changzhou, China
- Na Li
- Department of Oncology, Suining Central Hospital, Suining, China
- Yangyi Bao
- Department of Oncology, The First People's Hospital of Hefei, Hefei, China
- Yinyin Li
- First Department of Oncology, Shenyang Chest Hospital, Shenyang, China
- Yanjun Su
- Department of Pulmonary Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
- Min Zhao
- Oncology, Hebei Chest Hospital, Shijiazhuang, China
- Haohui Fang
- Respiratory, Anhui Chest Hospital, Hefei, China
- Yulong Zhu
- Department of Respiratory, Hospital of Traditional Chinese Medicine of Xinjiang Uygur Autonomous Region, Urumqi, China
- Yu Zhang
- Respiratory, Nanjing Chest Hospital, Nanjing, China
- Lieming Ding
- Betta pharmaceuticals Co., Ltd., Hangzhou, China
- Yang Wang
- Betta pharmaceuticals Co., Ltd., Hangzhou, China
- Xiaobin Yuan
- Betta pharmaceuticals Co., Ltd., Hangzhou, China
- Jie Wang
- State Key Laboratory of Molecular Oncology, 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, China; Corresponding Author: Jie Wang, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
- Journal volume & issue
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Vol. 42
p. 101187
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.
