Phase 2 Study of SPI-2012 or Pegfilgrastim for the Management of Neutropenia in Participants With Breast Cancer

Phase 2, Open-Label, Dose-Ranging Study of SPI-2012 (HM10460A) or Pegfilgrastim Use for the Management of Neutropenia in Patients With Breast Cancer Who Are Candidates for Adjuvant and Neoadjuvant Chemotherapy With the Docetaxel + Cyclophosphamide (TC) Regimen

The purpose of this study is to assess the effect of test doses of SPI-2012 on the duration of severe neutropenia (DSN) during Cycle 1 in participants with breast cancer who are candidates for adjuvant or neoadjuvant chemotherapy.

This is an open label, multicenter, dose ranging study, sequentially enrolled by study dose, with a non-inferiority design to compare the effectiveness of SPI-2012 relative to a fixed dose of pegfilgrastim as a concurrent active control to each dose of SPI-2012 in participants with breast cancer. This study included four arms comprising three dose levels of SPI-2012 (Arm 1: 45 µg/kg, Arm 2: 135 µg/kg, Arm 3: 270 µg/kg) versus pegfilgrastim (Arm 4: 6 mg). The start of study is defined as the initiation of treatment with SPI-2012 or pegfilgrastim. The duration of treatment consists of a maximum of 4 cycles (21 days per cycle) beginning on Day 1 with chemotherapy administration and continue through Day 21, plus a 30-day follow-up period, unless any of the discontinuation criteria applies.

The target population are participants with breast cancer who are candidates for neoadjuvant or adjuvant treatment with Docetaxel + Cyclophosphamide (TC) chemotherapy. All participants who receive at least 1 dose of either SPI-2012 or pegfilgrastim were followed for safety through 30 days after their last dose of study treatment or until all treatment-related adverse events (AEs) have resolved or returned to baseline/Grade 1, whichever is longer, or until it is determined that the outcome will not change with further follow-up.

Inclusion Criteria:

• Histologically confirmed breast cancer and candidate for adjuvant or neoadjuvant chemotherapy
• Candidate for docetaxel and cyclophosphamide chemotherapy
• Female or male at least 18 years of age
• Eastern Cooperative Oncology Group (ECOG) ≤ 2
• Absolute neutrophil count (ANC) ≥ 1.5×109/L
• Platelet count ≥ 100 x 10^9/L
• Creatinine ≤ 1.5 x upper limit of normal (ULN)
• Total bilirubin ≤1.5 mg/dL(≤ 25.65 μmol/L).
• Aspartate aminotransferase per serum glutamic-oxaloacetic transaminase (AST/SGOT) and/or alanine aminotransferase per serum glutamic-pyruvic transaminase (ALT/SGPT) ≤ 2.5 x ULN
• Hemoglobin > 9 g/dL
• Alkaline phosphatase ≤ 1.5 x ULN

Exclusion Criteria:

• Known sensitivity to E. coli-derived products or known sensitivity to any of the products to be administered
• Known Human Immunodeficiency Virus (HIV) infection
• Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) diagnosis with detectable viral load or immunological evidence of chronic active disease
• Active infection or any serious underlying medical condition that would impair ability to receive protocol treatment
• Prior bone marrow or stem cell transplant
• Prolonged exposure to glucocorticosteroids and immunosuppressive agents