Abstract P5-16-14: A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

Abstract Background: Neutropenia is common in patients receiving myelotoxic chemotherapy. F-627( efbemalenograstim alfa ), is a novel long acting dimeric 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 study was to evaluate the efficacy and safety of F-627 for reducing chemotherapy-induced neutropenia as compared with filgrastim (GRAN®). Methods: This was a multicenter, randomized, open-label, and active-controlled non-inferiority study. Thirteen centers enrolled 239 patients who received chemotherapy with epirubicin (100mg/m2) and cyclophosphamide (600 mg/m2) (EC therapy) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 3 either a single 20 mg subcutaneous (s.c.) injection of F-627 per cycle or daily s.c injections of filgrastim 5 μg/kg/day. The primary endpoint was the duration of grade 3 (ANC <1× 109/L) or 4 (ANC<0.5× 109/L) neutropenia in cycle 1. The safety profile was evaluated. Results: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.67 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimator of the median difference between groups (F-627 − Filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of one-sided 97.5% CI was 0 days, which was within the 1-day prespecified non-inferiority margin. Results for all efficacy end points in cycles 2−4 was consistent with the results from 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 with F-627 compared with filgrastim. The nadir in the F-627 group was higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as multiple daily doses of filgrastim. The most frequently reported adverse events considered to be related to the study drug were bone pain and back pain. No deaths occurred during the study. 5.0% of F-627 patients and 6.7% of filgrastim patients reported serious adverse events (SAEs). The incidence of SAEs was low in both groups and no SAEs were related to study drugs, and were resolved during the study. Conclusions: A single fixed dose of 20 mg of F-627 was as safe and effective as multiple daily doses of filgrastim 5μg/kg/day in reducing chemotherapy-induced neutropenia and its complications in patients who received four cycles of EC therapy. F-627 provides the Chinese oncologists an alternative for simplifying the management of chemotherapy-induced neutropenia. The study was approved by the National Medical Products Administration of China (registration number: 2017L04033), and was registered on www.chinadrugtrials.org.cn (registration number: CTR20170705) and ClinicalTrials.gov (registration number: NCT04174599). Citation Format: William Daley, Zhimin Shao, Qingyuan Zhang, Hongshen Li, Changshen Ye, Shufang Wang, Langxi Zhang, Gaochong Zhang, Jianmin Chen. A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-14.