Randomized Phase 2, Dose-finding Efficacy, Safety Study of ANF-RHO™ Versus Neulasta® in Chemotherapy-Induced Neutropenia

A Randomized and Open-label Dose-finding, Ph. 2, Efficacy, Safety, and Pharmacokinetic Study of Once-per-cycle Prophylactic Injections of ANF-RHO™ Versus Pegfilgrastim (Neulasta®) in Non-metastatic Breast Cancer Patients at High-risk of Chemotherapy-induced Neutropenia

Randomized, Open-Label study to determine the dose, efficacy, safety and pharmacokinetic profile of ANF-RHO™ with once-per-cycle injection in comparison with Neulasta in Breast Cancer patients at high risk of developing Chemotherapy-Induced Neutropenia

Forty Eight (48) adult female, chemotherapy treatment-naïve, stage I to III, breast cancer patients scheduled to receive FEC100 (3 cycles)/docetaxel (3 cycles) myelosuppressive chemotherapy will be enrolled into the study after they meet all the inclusion/exclusion criteria. Four (4) Cohorts of 12 patients each will be studied; they will be randomized either in the ANF-RHO™ treatment arm at different doses (10 μg/kg, 20 μg/kg, or 30 μg/kg, for the cohorts 1-3, respectively) or Neulasta® (6 mg / 0.6 ml SC injection, for cohort 4). For the cohorts 1-3, 12 patients from each of the respective ANF-RHO™ cohorts will be randomized with four patients from cohort 4 (Neulasta®). Patients in the ANF-RHO™ cohorts will receive study drug on Day 1 of each Chemotherapy cycle. Patients in the Neulasta® cohort will receive study drug on Day 2 of each Chemotherapy cycle. Doses of ANF-RHO™/Neulasta® will be provided for a total of 6 cycles (21 days each). The total duration of the study 129 ± 2 days (126 Days of treatment period followed by end of study visit)

Inclusion Criteria:

1. Adult female patients, 18 years of age or older

2. Signed and dated written consent/assent by the patient or legally authorized representative

3. Histologically confirmed non-metastatic breast cancer

4. ECOG performance status ≤ 2

5. Myelosuppressive chemotherapy naive

6. Scheduled to receive and anticipated to complete the following chemotherapy regimen

   1. FEC (fluorouracil/epirubicin (100) / cyclophosphamide) (3 cycles);
   2. Docetaxel (3 cycles) chemotherapy

7. White blood cells (WBC) ≥ 3 × 10^9/L; Absolute neutrophil count (ANC) ≥ 2.0 × 10^9/L; platelet count ≥ 100 × 10^9/L; and hemoglobin ≥ 10 g/dL (6.2 mmol/L)

8. Adequate cardiac function (e.g. LVEF > 50% as determined by standard care) and adequate hepatic function (e.g. liver transaminases < 2.5 x ULN)

9. Women of childbearing potential with a negative serum pregnancy test and using a highly effective method of birth control (i.e. one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives and intrauterine devices (IUDs)). Periodic abstinence is not an acceptable contraceptive method during the study period.

Exclusion Criteria: A subject will not be enrolled if any they meet any of the following criteria:

1. Known hypersensitivity to E.coli derived products or polyethylene glycol
2. No other malignancy except carcinoma in situ and basal-cell and squamous cell carcinoma of the skin, unless the other malignancy was treated ≥ 5 years ago with curative intent
3. Evidence of myelodysplasia, aplastic anemia, myelofibrosis, rheumatoid arthritis, systemic lupus erythematosus, or sickle cell disease
4. Clinical diagnosis or history of chronic infection such as hepatitis B virus (HBV), hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or history of tuberculosis
5. Previous exposure to filgrastim, perfilgrastim or lipegfilgrastim within 30 days before randomization
6. Treatment with systemically active antibiotics within 72 hours before chemotherapy
7. Chronic use of oral corticosteroids
8. Participation in a pharmacological clinical trial within 30 days before randomization
9. Clinical diagnosis of drug abuse or substance abuse within 30 days prior to screening
10. Documented alcohol abuse within 30 days prior to screening
11. Unwilling and/or not capable of ensuring compliance with the provisions of the study protocol
12. Pregnant or breastfeeding women where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive serum HCG laboratory test
13. Other serious medical condition that would prevent individual from receiving protocol treatment