Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia after Same-Day Dosing of Eflapegrastim in Patients with Breast Cancer Receiving Docetaxel and Cyclophosphamide (NCT04187898)

Background: Eflapegrastim (Rolontis®, Efla) is a long-acting granulocyte-colony stimulating factor (G-CSF), consisting of a recombinant human G-CSF analog conjugated to a human IgG4 Fc fragment via a short polyethylene glycol linker. Efla is not a biosimilar and represents the first myeloid growth factor innovation in more than 15 years. In preclinical studies with chemotherapy-induced neutropenic rats, Efla showed ~3-fold higher exposure in serum and higher exposure in bone marrow at similar doses compared to pegfilgrastim (Peg). The duration of neutropenia (DN) was shown to be significantly shorter with Efla vs Peg when administered on the same day or 24-hours post-chemotherapy. Additionally, the DN after Efla administered on the same day as chemotherapy was similar to the DN 24 hours post-chemotherapy. Moreover, in two Phase 3 studies that randomized a total of 643 patients with early-stage breast cancer (ESBC) to either Efla (3.6 mg G-CSF n=314) or Peg (6 mg G-CSF n=329) given ~ 24 hours after docetaxel and cyclophosphamide (TC), the duration of severe neutropenia (DSN) was statistically noninferior in patients treated with Efla compared to Peg. As a standard of practice, G-CSF products require administration 24 hours after chemotherapy. Since Efla preclinical and clinical results suggest that the increased activity of Efla may provide effective prophylaxis against chemotherapy-induced neutropenia when administered on the same day as chemotherapy, the purpose of this study is to assess the feasibility of giving Efla same-day (at 3 different dosing timepoints) in patients receiving TC for the treatment of ESBC. Study Design and Methods: This is a randomized, schedule finding, multicenter, Phase 1, open-label study evaluating the same-day administration of 13.2 mg/0.6 mL Efla following IV infusion of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) in patients with ESBC. Treatment: On Cycle 1, Day 1, patients will be randomized 1:1:1 to Efla dose administration schedules of 0.5, 3, and 5 hours after TC. In Cycles 2-4, Efla will be administered ~ 24 hours following the administration of TC for all treatment arms. Clinical Endpoints: The primary endpoint is DSN (ANC