Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After Same-Day Dosing of Eflapegrastim in Patients With Breast-Cancer

Open-Label, Phase 1 Study to Evaluate Duration of Severe Neutropenia After the Same-Day, Varying Dosing Time Schedules of Eflapegrastim Administration in Patients With Breast-Cancer Receiving Docetaxel and Cyclophosphamide

The purpose of this study is to compare the effect of Eflapegrastim on duration of neutropenia in patients with early-stage breast cancer when administered at varying intervals following Docetaxel and Cyclophosphamide administration.

This is a Phase 1, randomized, open label, actively-controlled study to evaluate the same day dosing of Eflapegrastim on duration of neutropenia when administered at varying intervals following Docetaxel and Cyclophosphamide (TC) chemotherapy in patients with early-stage breast cancer.

The study will be conducted in two phases: Early Phase and Expansion Phase.

1. In the Early Phase, approximately 45 patients were enrolled and randomized in a 1:1:1 ratio to 3 dosing time schedule arms. Each cycle was of 21 days. Total 4 cycles were evaluated for this phase. On Day 1 of Cycle 1, patients received Docetaxel and Cyclophosphamide (TC) chemotherapy followed by administration of Eflapegrastim at 1 of 3-time schedules post-TC (30 minutes [mins], 3 hours or 5 hours). During Cycles 2-4, patients received Eflapegrastim 24 hours after TC administration (on Day 2).
2. In the Expansion Phase, additional 45 patients will be enrolled in Cycles 1-4, who will receive fixed dose of Eflapegrastim 30 mins after TC administration (on Day 1).

Safety evaluations will be conducted once the first 3 patients (for Early Phase) and the first 6 patients (for Expansion Phase) have completed Cycle 1 to determine if it is safe for patients to continue in that particular treatment arm.

Inclusion Criteria:

• Willing and capable of giving written Informed Consent and able to adhere to study drug dosing time and blood draw schedules
• New diagnosis of histologically confirmed early-stage breast cancer (ESBC), defined as operable Stage I to Stage IIIA breast cancer
• Candidate to receive adjuvant or neoadjuvant TC chemotherapy
• Age must be at least 18 years for the Early Phase, and between 18 to ≤55 years for the Expansion Phase
• ANC ≥1.5×10^9/liter (L).
• Platelet count ≥100×10^9/liter (L).
• Hemoglobin >10 grams per deciliter (g/dL).
• Calculated creatinine clearance >50 milliliter per minute (mL/min).
• Total bilirubin ≤1.5 milligrams per deciliter (mg/dL).
• Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) ≤2.5×upper limit of normal (ULN).
• Alkaline phosphatase ≤2.0×ULN.
• Eastern Cooperative Oncology Group (ECOG) ≤2
• Willing to practice 2 forms of contraceptives (1 must be a barrier method), from study entry through 30 days after last dose of study drug/ early discontinuation
• Negative urine pregnancy test within 30 days before randomization

Exclusion Criteria:

• Active concurrent malignancy (except non melanoma skin cancer or carcinoma in situ of the cervix) or life-threatening disease
• Known sensitivity to Escherichia coli (E. coli) derived products
• Concurrent adjuvant cancer therapy other than the trial-specified therapies
• Locally recurrent/metastatic breast cancer
• Previous exposure to filgrastim, pegfilgrastim, or other G-CSF products in clinical development within 3 months prior to the administration of study drug
• Receiving anti-infectives, has an underlying medical condition or other serious illness that would impair the ability to receive protocol-specified treatment
• Used any investigational drugs, biologics, or devices within 30 days prior to study treatment or plans to use any of these during the course of the study
• Prior bone marrow or stem cell transplant
• Prior radiation therapy within 30 days prior to enrollment
• Major surgery within 30 days prior to enrollment
• Pregnant or breastfeeding