A randomized, noninferiority study of recombinant human G-CSF/human serum albumin fusion (CG-10639) and pegfilgrastim in breast cancer patients receiving myelosuppressive therapy.

Abstract

9083 Background: Teva’s CG-10639 is a long-acting recombinant human albumin-human granulocyte-colony stimulating factor under investigation to prevent chemotherapy-induced neutropenia. Similar to pegfilgrastim (PEGF), CG-10639 stimulates neutrophil and hematopoietic stem cell mobilization from bone marrow to peripheral blood. No clinically relevant immunogenicity with CG-10639 has been observed to date. The main objective of this study was to evaluate the safety and effectiveness of CG-10639 versus PEGF in breast cancer patients (BCA pts) receiving myelosuppressive therapy. Methods: This phase II/III study was a randomized, multi-center, active controlled trial in 334 BCA pts receiving doxorubicin/docetaxel (DOX/DOC). The study included a pilot dose escalation phase to identify two CG-10639 doses with similar effects to PEGF (6mg), and a main phase powered for efficacy (non-inferiority). During the pilot phase, patients were randomized to receive CG-10639 30mg or PEGF one day after DOX/DOC followed by additional cohorts receiving CG-10639 40mg, 50mg. The main phase of the study used a randomized, 3-arm parallel design comparing two doses of CG-10639 and PEGF following DOX 60mg/m2 and DOC 75mg/m2 IV on day 1 for up to four 21-day cycles. The primary endpoint was the duration of severe neutropenia (DSN) during cycle 1 in days (d). Results: In the pilot phase (n=78) DSN, secondary efficacy parameters and safety were similar across all treatments. CG-10639 40mg and 50mg doses were selected for further investigation. In the main phase (n=256), there were no statistically significant differences in mean DSN between CG-10639 40mg (1.0d), CG-10639 50mg (1.3d), and PEGF (1.2d) in Cycle 1. In each cycle, efficacy was comparable based on ANC nadir and recovery, the incidence and duration of Grade 3 or 4 neutropenia, and the incidence of febrile neutropenia. The type and frequency of treatment emergent AEs were similar across treatment groups. Conclusions: These results support the conclusion that CG-10639 is non-inferior to PEGF based on mean DSN in BCA pts receiving myelosuppressive therapy. The overall safety profile was similar for CG-10639 and PEGF. A phase III, confirmatory study comparing CG-10639 40mg to PEGF 6mg is underway.