Journal Article

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

Yang, Hongjian, Geng, Cuizhi, Zhang, Gaochong, Chen, Jianmin, Sun, Tao, Yao, Wei, Chen, Zhendong, Ye, Changsheng, Li, Hongsheng, Zhang, Jin, Wang, Shufang, Wang, Zhonghua, Zhang, Qingyuan, Shao, Zhimin, Wang, Zhihong, Li, Xingrui, Li, Simon, Liu, Xiaoan, Zheng, Hong, Hou, Qingsong

2024

Overview

Background 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®). Methods 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/m 2 ) and cyclophosphamide (600 mg/m 2 ) 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. Results 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. Conclusions 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. Trial registration ClinicalTrials.gov: NCT04174599, on 22/11/2019.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Adult / Aged / Amino acids / Analysis / Antibiotics / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - drug therapy / Cancer / Cancer Research / Cancer therapies / Care and treatment / Chemotherapy / Clinical significance / Colony-stimulating factor / Complications and side effects / Creatinine / Cyclophosphamide / Cyclophosphamide - administration & dosage / Cyclophosphamide - adverse effects / Diagnosis / Drug Administration Schedule / Drug dosages / Drug therapy / Efbemalenograstim alfa / Epirubicin / Epirubicin - administration & dosage / Epirubicin - adverse effects / F-627 / Female / Filgrastim / Filgrastim - administration & dosage / Filgrastim - adverse effects / Filgrastim - therapeutic use / G-CSF / Granulocyte colony-stimulating factor / Granulocyte Colony-Stimulating Factor - administration & dosage / Granulocyte Colony-Stimulating Factor - therapeutic use / Granulocytes / Health Promotion and Disease Prevention / Hepatitis / Humans / Immunoglobulin G2 / Infections / Leukocytes (granulocytic) / Medicine/Public Health / Middle Aged / Multicenter study / Neutropenia / Neutropenia - chemically induced / Neutropenia - prevention & control / Neutrophils / Oncology / Patients / Peptides / Prophylaxis / Recombinant Fusion Proteins - administration & dosage / Recombinant Fusion Proteins - therapeutic use / Risk factors / Surgical Oncology