Abstract OT1-01-11: Randomized phase 3 study of a novel, long-acting G-CSF (eflapegrastim) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study)
Authors: Schwartzberg LS , Bharadwaj J , Peguero JA , Vacirca JL , Ibrahim EN , Bhat G , Choi MR , McGregor K , Agajanian R 
Published: March 2017

Abstract
Background: Eflapegrastim is a distinct biologic that uses an innovative, proprietary long-acting protein/peptide discovery technology (LAPSCOVERY™). Eflapegrastim consists of a novel, modified recombinant human G-CSF conjugated to the Fc fragment of IgG4 via a polyethylene glycol linker to produce a new, longer-acting G-CSF with a potentially unique distribution to areas rich in Fc receptors including its site of action in the bone marrow. A successful dose-finding Phase 2 trial including a pegfilgrastim control arm established the dose for a Phase 3 non-inferiority trial.
Trial Design: This is a randomized, open-label, active-controlled, multinational, multicenter, Phase 3 study comparing the efficacy and safety of eflapegrastim to pegfilgrastim. Patients (n=580) will be randomized in a 1:1 ratio to receive either eflapegrastim (equivalent to 3.6 mg G-CSF) or pegfilgrastim (equivalent to 6.0 mg G-CSF) once per chemotherapy cycle (up to 4 cycles), approximately 24 hours after chemotherapy. The primary endpoint is to compare the efficacy of a single dose of eflapegrastim with pegfilgrastim in patients with ESBC receiving TC, as measured by the Duration of Severe Neutropenia (DSN) in Cycle 1. Key secondary objectives include Time to Absolute Neutrophil Count (ANC) Recovery in Cycle 1; Depth of ANC Nadir in Cycle 1; incidence of Febrile Neutropenia. Safety and pharmacokinetics will also be assessed.
Eligibility Criteria: This study is enrolling histologically confirmed ESBC patients who are: eligible to receive adjuvant or neoadjuvant TC chemotherapy; at least 18 years of age, with adequate hematologic, renal and hepatic function. Patients will be excluded if they have: active concurrent malignancy or life-threatening disease; a known sensitivity or previous reaction to E. coli derived products or any of the products to be administered during study participation; concurrent adjuvant cancer therapy; locally recurrent/metastatic or contralateral breast cancer; previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development prior to the administration of study drug; bone marrow or hematopoietic stem cell transplant or radiation therapy prior to enrollment, or are pregnant or breast-feeding.
Statistical Methods: The goal of this study is to demonstrate non-inferiority. For the Primary Efficacy Analysis, the mean DSN in Cycle 1 will be compared between the eflapegrastim and pegfilgrastim treatment arms. A 2-sided 95% confidence interval (CI) of the difference between the mean DSN of the eflapegrastim arm and the mean DSN of the pegfilgrastim arm will be calculated using bootstrap resampling with treatment as the only stratification factor. For the Secondary Efficacy Analyses, the results will each be summarized by treatment arm and cycle. The two-sided 95% CI for the difference between the treatment arms will be calculated.
Target Accrual: Approximately 580 patients. Enrollment began January 2016.
Contact Information: Spectrum Pharmaceuticals. advance@sppirx.com.
Citation Format: Schwartzberg LS, Bharadwaj J, Peguero JA, Vacirca JL, Ibrahim EN, Bhat G, Choi MR, McGregor K, Agajanian R. Randomized phase 3 study of a novel, long-acting G-CSF (eflapegrastim) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr OT1-01-11.