30 Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After Same-Day Dosing of Eflapegrastim in Patients With Early- Stage Breast Cancer (ESBC) Receiving Docetaxel and Cyclophosphamide

Lee S. Schwartzberg, MD¹;Lyndah K. Dreiling, MD²; Jawad Francis, MD³; Nishan Tchekmedyian, MD⁴; Osama Hlalah, MD⁵; Manuel Modiano, MD⁶; Gajanan Bhat, PhD²; Francois Lebel, MD²; Shanta Chawla, MD²

¹West Cancer Center, Germantown, TN.

²Spectrum Pharmaceuticals, Inc, Irvine, CA.

³Mercy Health Youngstown, Youngstown, OH.

⁴Pacific Shores Medical Group, Huntington Beach, CA.

⁵Bond & Steele Clinic, PA, Winter Haven, FL.

⁶Arizona Clinical Research Center, Tucson, AZ.

Background

Eflapegrastim (Efla) is a long-acting granulocyte colony-stimulating factor (G-CSF), produced by covalent conjugation of a human GCSF analogue and a human immunoglobulin G4 Fc fragment, linked via a short polyethylene glycol linker. Currently available G-CSFs are administered 24 hours after chemotherapy. In docetaxel and cyclophosphamide (TC)–induced neutropenia in rats, the longer marrow residence time of Efla compared with pegfilgrastim translated into shorter duration of neutropenia when administered on the same day as TC. Data from the interim safety analysis in patients receiving Efla on the same day as chemotherapy are presented.

Materials and Methods

This is a randomized, schedule-finding, multicenter study (NCT04187898) evaluating same-day administration of 13.2 mg/0.6 mL Efla following intravenous infusion of docetaxel (75 mg/m2) and cyclophosphamide (600 mg/m2) in patients with ESBC. Patients were randomized to receive Efla 0.5 hours (Arm 1), 3 hours (Arm 2), and 5 hours (Arm 3) after TC. The primary end point is duration of grade 4 neutropenia (DSN) in cycle 1. The secondary end points include incidence of grade 3 febrile neutropenia (FN), pharmacokinetics, and safety in cycle 1. At the interim safety evaluation, an arm would be stopped if 1 or more patients experienced grade 4 DSN for more than 1 day.

Results

The interim evaluation, per protocol, included 9 patients (3 in each arm). In Arm 1, 1 of 3 patients had grade 4 neutropenia for 1 day without FN. In Arm 2, 1 of 3 patients had grade 4 neutropenia for 2 days and FN for 1 day with sepsis. In Arm 3, 1 of 3 patients had grade 4 neutropenia for 2 days and FN for 1 day, and another patient had grade 4 neutropenia for 1 day without FN. All 9 patients reported at least 1 adverse event (AE). Related grade 3 AEs included bone pain in 1 patient (arm 2) and lymphocyte count decreased in 1 patient (arm 3). There were no serious AEs related to Efla.

Conclusions

Efla may provide similar efficacy when administered on the same day, rather than next day, following TC. At interim evaluation, Arm 1 had no grade 4 neutropenia lasting more than 1 day. Enrollment in Arms 2 and 3 was discontinued because of the presence of grade 4 neutropenia that lasted more than 1 day and the overall safety profile. Enrollment is ongoing in Arm 1.