A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

IF 3.4 2区 医学 Q2 ONCOLOGY BMC Cancer Pub Date : 2024-09-13 DOI:10.1186/s12885-024-12892-5
Qingyuan Zhang, Zhonghua Wang, Wei Yao, Shufang Wang, Gaochong Zhang, Jianmin Chen, Qingsong Hou, Simon Li, Hongsheng Li, Changsheng Ye, Tao Sun, Hongjian Yang, Zhendong Chen, Zhihong Wang, Xiaoan Liu, Cuizhi Geng, Xingrui Li, Jin Zhang, Hong Zheng, Zhimin Shao
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Abstract

F-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®). This was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated. The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim. A single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC. ClinicalTrials.gov: NCT04174599, on 22/11/2019.
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新型长效 rhG-CSF efbemalenograstim alfa (F-627) 用于预防乳腺癌患者化疗所致中性粒细胞减少症的每周期一次随机多中心 III 期研究
F-627(efbemalenograstim alfa)是一种新型长效粒细胞集落刺激因子(G-CSF),它含有两个融合了人免疫球蛋白 G2 (hIgG2) -Fc 片段和一个肽连接体的人 G-CSF。这项研究评估了 F-627(又称 efbemalenograstim alfa (Ryzneuta®))与 filgrastim (GRAN®) 相比在减少中性粒细胞减少症方面的有效性和安全性。这是一项多中心、随机、开放标签、主动对照的非劣效性研究。13个中心共招募了239名患者,他们在每个周期的第1天接受表柔比星(100毫克/平方米)和环磷酰胺(600毫克/平方米)化疗,最多四个周期。患者被随机分配在每个周期的第3天接受单次20毫克的F-627皮下注射,或从每个周期的第3天开始每天接受5微克/千克/天的filgrastim皮下注射。主要终点是第一周期中3级或4级中性粒细胞减少的持续时间。此外,还对安全性进行了评估。F-627组和filgrastim组第一周期3级或4级中性粒细胞减少的平均(标度)持续时间分别为0.68(1.10)天和0.71(0.95)天。第1周期3级或4级中性粒细胞减少持续时间的组间中位数差异(F-627 vs filgrastim)的霍奇斯-莱曼估计值为0天,单侧97.5% CI的上限为0天,在1天的预设非劣效边限内。第2-4周期所有疗效终点的结果与第1周期的结果一致,但与非格司亭组相比,F-627组3级或4级中性粒细胞减少症和4级中性粒细胞减少症的发生率更低,持续时间更短。在每个周期中,F-627组的ANC最低值都明显高于filgrastim组。单次固定剂量的F-627耐受性良好,与每日标准剂量的非格司亭一样安全。在接受四个周期EC治疗的患者中,在减少中性粒细胞减少症及其并发症方面,每个周期单次固定剂量20毫克F-627与每日剂量5微克/千克/天的filgrastim同样安全有效。临床试验NCT04174599,2019年11月22日。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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