Abstract P1-10-05: Randomized phase 2, open-label, dose-ranging study of a novel, long-acting G-CSF (SPI-2012) or pegfilgrastim for the management of neutropenia in patients with breast cancer (BC) treated with (Neo) adjuvant chemotherapy with docetaxel + cyclophosphamide (TC)
Authors: Vacirca JL , Chan A , Mezei K , Adoo CS , Papai Z , McGregor K , Okera M , Horvath Z , Landherr L , Hanslik J , Hager SJ , Ibrahim EN , Ghazal H , Rostom M , Bhat G , Choi MR , Allen LF , Tedesco KL , Agajanian R , Lang I 
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. To assess the effect of SPI-2012 in supporting patients with breast cancer receiving myelosuppressive chemotherapy with TC, we conducted a randomized Phase 2 study of 3 SPI-2012 doses versus pegfilgrastim.
Methods: This was an open-label, global, multicenter, dose-ranging study designed to compare the safety and efficacy of SPI-2012 relative to a fixed, standard dose of pegfilgrastim as a concurrent active control. The study included 4 treatment arms: 3 dose levels of SPI-2012 (45 μg/kg, 135 μg/kg, and 270 μg/kg) vs pegfilgrastim (6 mg,). The primary objective of the study was the Duration of Severe Neutropenia (DSN) during Cycle 1 in patients with BC who received adjuvant or neoadjuvant TC chemotherapy.
Results: A total of 147 evaluable patients were enrolled. Patient and tumor characteristics were comparable across all 4 treatment arms. Mean age was 58.2 years (range 32 to 77 years); most patients were &lt;65 years (68%), female (98%) and white (95%). The study met its primary endpoint with DSN in patients treated in the 135 µg/kg and 270 µg/kg SPI-2012 treatment arms in Cycle 1 showing non-inferiority to the DSN in patients treated with pegfilgrastim (p=0.002 and p&lt;0.001, respectively). In addition, superiority was demonstrated in patients treated with 270 µg/kg SPI-2012 compared to pegfilgrastim (p=0.023). Non-inferiority in DSN was also observed in Cycles 2 to 4 in both the 135 µg/kg and 270 µg/kg SPI-2012 treatment arms compared to pegfilgrastim.
Duration of Severe Neutropenia in Cycle 1 of TC chemotherapy by Treatment Arm 45 μg/kg SPI-2012 (N=39) 135 μg/kg SPI-2012 (N=36) 270 μg/kg SPI-2012 (N=36)Pegfilgrastim (N=36)DSN Mean (SD)(days)1.03 (1.5)0.44 (1.3)0.03 (0.2)0.31 (0.8)Difference with pegfilgrastim0.720.14-0.28NANon-inferiority p-value0.2960.002&lt;0.001NASuperiority p-value0.0060.5280.023NASD=Standard Deviation; NA=Not Applicable
The common treatment-emergent adverse events observed in ≥20% of patients were similar across all 4 study arms with similar or lower incidence in the SPI-2012 treatment arms, and included fatigue, nausea, alopecia, diarrhea, and bone pain.
Conclusions: All doses of SPI-2012 administered in this Phase 2 study were well tolerated, and no new or significant dose-related toxicities were observed. Most reported adverse events were mild and similar to those previously reported in clinical trials with filgrastim and pegfilgrastim in patients receiving myelosuppressive chemotherapy. In Cycle 1, the 135 µg/kg dose of SPI-2012 was non-inferior compared to pegfilgrastim, and the 270 µg/kg dose was superior in terms of DSN. Additional efficacy and safety data for SPI-2012 will be collected in planned Phase 3 clinical trials.
Citation Format: Vacirca JL, Chan A, Mezei K, Adoo CS, Papai Z, McGregor K, Okera M, Horvath Z, Landherr L, Hanslik J, Hager SJ, Ibrahim EN, Ghazal H, Rostom M, Bhat G, Choi MR, Allen LF, Tedesco KL, Agajanian R, Lang I. Randomized phase 2, open-label, dose-ranging study of a novel, long-acting G-CSF (SPI-2012) or pegfilgrastim for the management of neutropenia in patients with breast cancer (BC) treated with (Neo) adjuvant chemotherapy with docetaxel + cyclophosphamide (TC). [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 P1-10-05.