Safety and efficacy of eflapegrastim in reducing severe neutropenia in patients treated with myelosuppressive chemotherapy in a phase 3 randomized controlled trial compared to pegfilgrastim (ADVANCE trial).

e12513 Background: Eflapegrastim is a novel investigational biologic comprised of recombinant human G-CSF covalently linked to the human immunoglobulin G4FC fragment using proprietary LAPSCOVERY™ technology with potentially unique distribution to areas rich in FcRn receptors. The current study was a randomized, phase 3 study to demonstrate the non-inferiority (NI) of eflapegrastim to pegfilgrastim in patients receiving chemotherapy for breast cancer. Methods: Patients with Stage I to Stage IIIA breast cancer were treated on Day 1 of each of four cycles with adjuvant/neo-adjuvant docetaxel and cyclophosphamide (TC). On Day 2 of each cycle patients received a single subcutaneous dose of either eflapegrastim 13.2 mg/0.6 mL (equivalent to 3.6 mg G-CSF) or pegfilgrastim (6 mg) in a 1:1 ratio. Patients had CBCs drawn daily on Day 1 and day 4-15 or until recovery of neutropenia in each cycle. The primary endpoint was to demonstrate non-inferiority of eflapegrastim to pegfilgrastim as measured by the mean duration of severe neutropenia (DSN) in Cycle 1 with NI margin of < 0.62 day. Results: In a total of 406 intent-to-treat patients (randomized to 196 eflapegrastim; 210 pegfilgrastim), median age was 61 years (range 24 to 84 years); mean (SD) DSN was 0.19 (0.478) days for eflapegrastim and 0.34 (0.668) days for pegfilgrastim, demonstrating the non-inferiority (95% CI of ∆DSN: [-0.260, -0.035]; p < 0.0001). The non-inferiority of eflapegrastim for DSN was maintained across all 4 cycles. There were no statistically significant differences in secondary endpoints of time to ANC recovery, depth of ANC nadir and incidence of FN at Cycle 1. The adverse events observed in ≥10% of patients were similar across both arms and were mainly hematologic including neutropenia, lymphopenia, anemia and leukopenia. Conclusions: Eflapegrastim, a novel long acting G-CSF was non-inferior to pegfilgrastim in the reduction of DSN in Cycles 1-4, in breast cancer patients treated with TC. Eflapegrastim was safe and well-tolerated with a similar safety profile to pegfilgrastim. Clinical trial information: NCT02643420.