Abstract OT3-02-13: Randomized phase 3 study of a novel, long-acting G-CSF (SPI-2012) versus pegfilgrastim in the management of chemotherapy-induced neutropenia in early-stage breast cancer patients receiving docetaxel and cyclophosphamide (TC) (ADVANCE study)
Authors: Schwartzberg L , Vacirca JL , Hager SJ , Adoo CS , Ibrahim EN , Bhat G , Choi MR , Allen LF , Tedesco KL , Agajanian R 
Published: May 2016

Abstract
Background: SPI-2012 is a distinct biologic that uses the innovative, proprietary long-acting protein/peptide discovery technology (LAPSCOVERY™) to enhance the activity of G-CSF. SPI-2012 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, more potent, longer-acting G-CSF with a potentially unique distribution to areas rich in Fc receptors. The primary endpoint of this Phase 3 study is to compare the efficacy of a single dose of SPI-2012 with pegfilgrastim in patients with early-stage breast cancer (ESBC) receiving TC chemotherapy, as measured by the Duration of Severe Neutropenia (DSN) in Cycle 1. Key secondary objectives include the comparison of SPI-2012 with pegfilgrastim during Cycle 1 in: Time to Absolute Neutrophil Count (ANC) Recovery; Depth of ANC Nadir and Incidence of Febrile Neutropenia. Safety and pharmacokinetics will also be assessed.
Trial Design: This is a randomized, open-label, active-controlled, multicenter study comparing the efficacy and safety of SPI-2012 to pegfilgrastim. Patients (n=506) will be randomized in a 1:1 ratio to receive either SPI-2012 (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 hrs after chemotherapy.
Eligibility Criteria: This study will enroll histologically confirmed ESBC patients who are eligible to receive adjuvant or neoadjuvant TC chemotherapy and 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 the study is to demonstrate non-inferiority of SPI-2012 to pegfilgrastim. For the Primary Efficacy Analysis, the mean DSN in Cycle 1 will be compared between the SPI-2012 and pegfilgrastim treatment arms. A 2-sided 95% confidence interval (CI) of the difference between the mean DSN of the SPI-2012 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 506 pts.
Citation Format: Schwartzberg L, Vacirca JL, Hager SJ, Adoo CS, Ibrahim EN, Bhat G, Choi MR, Allen LF, Tedesco KL, Agajanian R. Randomized phase 3 study of a novel, long-acting G-CSF (SPI-2012) 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 Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-02-13.