Shukui Qin1, Jin Li2, Yuxian Bai3, Yongqian Shu4, Wei Li5, Xianli Yin6, Ying Cheng7, Guoping Sun8, Yanhong Deng9, Haijun Zhong10, Yunfeng Li11, Xiaoping Qian12, Liangming Zhang13, Jingdong Zhang14, Kehe Chen15, Wenying Kang16. 1. Department of Oncology, Qinhuai Medical Area, Eastern Theater General Hospital of PLA China, Nanjing, China. 2. Department of Medical Oncology, Tongji University Shanghai East Hospital, No. 1800 Yuntai Road, Pudong New Area, Shanghai, China. lijin@csco.org.cn. 3. Department of Gastroenterology, Harbin Medical University Cancer Hospital, Harbin, China. 4. Department of Oncology, Jiangsu Province Hospital, Nanjing, China. 5. Department of Oncology, The First Hospital of Jilin University, Changchun, China. 6. Department of Gastroenterology and Urology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, China. 7. Department of Internal Medicine, Jilin Cancer Hospital, Changchun, China. 8. Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei, China. 9. Department of Medical Oncology, The Sixth Affiliated Hospital (Guangdong Gastrointestinal Hospital), Sun Yat-sen University, Guangzhou, China. 10. Department of Medical Oncology, Zhejiang Cancer Hospital, Hangzhou, China. 11. Department of Colorectal Surgery, Yunnan Cancer Hospital, Kunming, China. 12. The Comprehensive Cancer Center of Nanjing Drum Tower Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China. 13. Department of Medical Oncology, The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China. 14. Medical Oncology Department of Gastrointestinal Tumors, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China. 15. Department of Chemotherapy Division II in Clinical Tumor Center, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China. 16. Shanghai Henlius Biotech, Inc., Shanghai, China.
Abstract
BACKGROUND:HLX04 is a proposed biosimilar of bevacizumab. OBJECTIVE: This phase III study aimed to evaluate the efficacy, safety, and immunogenicity of HLX04 compared with reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment for recurrent/metastatic colorectal cancer (CRC). METHODS: In this double-blind, parallel-group study, patients were randomized 1:1 to receive HLX04 or bevacizumab (7.5 mg/kg every 3 weeks when combined with XELOX; 5 mg/kg every 2 weeks when combined with mFOLFOX6). The primary endpoint was progression-free survival rate at week 36 (PFSR36w) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Prespecified equivalence margins of PFSR36w were set as - 11 to 15% (rate difference) and 0.8 to 1.25 (rate ratio). Secondary endpoints included efficacy, safety, immunogenicity, and pharmacokinetics. RESULTS: A total of 677 patients were randomized (HLX04 n = 340; bevacizumab n = 337) between April 2018 and April 2020. PFSR36w was 46.4% (95% confidence interval [CI] 41.1-51.8) with HLX04 and 50.7% (95% CI 45.4-56.1) with bevacizumab. The rate difference (- 4.2%; 90% CI - 10.6 to 2.1) and rate ratio (0.92; 90% CI 0.80-1.05) both fell within the prespecified equivalence margins. No notable differences were observed between treatment groups in any efficacy endpoints or their subgroup analyses. Safety, immunogenicity, and pharmacokinetic profiles were comparable between the two treatment groups. CONCLUSIONS:HLX04 demonstrated equivalent efficacy with similar safety and immunogenicity profiles to reference bevacizumab among patients with recurrent/metastatic CRC, thus offering an alternative treatment option to patients. TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20171503 (18 March 2018); ClinicalTrials.gov, NCT03511963 (30 April 2018).
RCT Entities:
BACKGROUND: HLX04 is a proposed biosimilar of bevacizumab. OBJECTIVE: This phase III study aimed to evaluate the efficacy, safety, and immunogenicity of HLX04 compared with reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment for recurrent/metastatic colorectal cancer (CRC). METHODS: In this double-blind, parallel-group study, patients were randomized 1:1 to receive HLX04 or bevacizumab (7.5 mg/kg every 3 weeks when combined with XELOX; 5 mg/kg every 2 weeks when combined with mFOLFOX6). The primary endpoint was progression-free survival rate at week 36 (PFSR36w) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1). Prespecified equivalence margins of PFSR36w were set as - 11 to 15% (rate difference) and 0.8 to 1.25 (rate ratio). Secondary endpoints included efficacy, safety, immunogenicity, and pharmacokinetics. RESULTS: A total of 677 patients were randomized (HLX04 n = 340; bevacizumab n = 337) between April 2018 and April 2020. PFSR36w was 46.4% (95% confidence interval [CI] 41.1-51.8) with HLX04 and 50.7% (95% CI 45.4-56.1) with bevacizumab. The rate difference (- 4.2%; 90% CI - 10.6 to 2.1) and rate ratio (0.92; 90% CI 0.80-1.05) both fell within the prespecified equivalence margins. No notable differences were observed between treatment groups in any efficacy endpoints or their subgroup analyses. Safety, immunogenicity, and pharmacokinetic profiles were comparable between the two treatment groups. CONCLUSIONS: HLX04 demonstrated equivalent efficacy with similar safety and immunogenicity profiles to reference bevacizumab among patients with recurrent/metastatic CRC, thus offering an alternative treatment option to patients. TRIAL REGISTRATION: Chinadrugtrials.org.cn, CTR20171503 (18 March 2018); ClinicalTrials.gov, NCT03511963 (30 April 2018).
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