Abstract CT116: Same-day administration of Eflapegrastim with chemotherapy enhances neutropenic recovery in neutropenic rats and in early-stage breast cancer patients

Abstract

Abstract Background: Chemotherapy-induced neutropenia increases the likelihood of life-threatening infections. Currently, long-acting G-CSF products are administered 24 hours after chemotherapy (CT). Eflapegrastim's (Efla) greater marrow resident time should provide a pharmacodynamic advantage over pegfilgrastim (Peg), translating into a shorter duration of neutropenia (DN). The therapeutic potential of Efla, a long-acting G-CSF, was evaluated in a neutropenic rat model where neutropenia was induced via intraperitoneal docetaxel/cyclophosphamide. This study compared the DN with that of vehicle control and Peg at 0, 2, 5, and 24 hrs post-CT. We found that at all-time points, there was a marked reduction in the degree of neutropenia and a more rapid rate of absolute neutrophil count (ANC) recovery with Efla compared to Peg. When Efla was administered concomitantly with CT, ANC returned to normal within 12hrs for Efla vs 2.2 days post-nadir for Peg, while the DN in the vehicle group was 7 days. Pharmacokinetics (PK) of Efla for same-day dosing were similar to those reported for next-day dosing. Based on these results, a Phase 1 clinical trial is ongoing; results for the first 9 patients are reported. Material and Methods: Phase 1, open-label study where Efla is administered at a fixed dose of 13.2 mg at 0.5, 3, and 5 hours s.c. after the i.v. infusion of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) CT in patients with confirmed stage I-IIIA breast cancer. Patients >18 years, ECOG <2, adequate hematological, renal, hepatic function & candidates for neoadjuvant or adjuvant CT were randomized 1:1:1 to Efla dose schedules. The primary endpoint was the duration of severe neutropenia (DSN) in Cycle 1. Secondary endpoints include incidence of Grade 3 febrile neutropenia (FN), PK & safety in Cycle 1. Results: Nine patients (3 patients per cohort) were enrolled. Protocol defined dose-limiting toxicity was not met in any cohort. One patient each in the 3 hr and 5 hr cohorts, developed severe neutropenia and FN. The PK of Efla for patients in the same-day dosing cohorts were similar to those observed for next-day dosing, as predicted by neutropenic rat results. Conclusions: Results to date from both nonclinical and clinical studies were similar and support our hypothesis that the higher and more sustained marrow resident time of Efla appears to provide an effective prophylaxis against severe neutropenia when administered on the same day as CT. The 0.5 hour cohort of the study is being expanded to confirm these promising results. Citation Format: John A. Barrett, Shanta Chawla, Prasad S. Kolli, Yu- Yon Kim, Sri Lakshmikanthan, Meera Tugnait, Lyndah K. Dreiling, Francois Lebel. Same-day administration of Eflapegrastim with chemotherapy enhances neutropenic recovery in neutropenic rats and in early-stage breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT116.