Efficacy and Safety Study of NeuVax(TM)(Nelipepimut-S or E75) Vaccine to Prevent Breast Cancer Recurrence (PRESENT)

Purpose of this trial:

1. To assess the efficacy and safety of NeuVax(TM)a peptide (E75) vaccine administered with adjuvant Leukine(R)(sargramostim,GM-CSF).
2. To evaluate and compare the disease free survival (DFS) in the vaccinated patients and control patients.

This is a multicenter, multinational, prospective, randomized, double-blind, controlled Phase 3 study.

The subjects eligible for this trial have an early stage Node-Positive (NP) breast cancer. Their tumors express low or intermediate levels of the HER2 protein. NeuVax™ will be administered after completion of front-line, standard of care therapy (surgery, radiation therapy, and chemotherapy) and can be given with physician prescribed endocrine treatment.

The NeuVax will be administered in intradermal injections, in four divided doses (4 sites on upper thigh) once a month, for six consecutive months. At the end of the six months, NeuVax vaccine boosters will be given the same way once every six months for the next five times (totaling 36 months).

The active portion of the study will last three years (36 months). The follow-up will last from 5 to 10 years.

Endpoints:

1. The primary efficacy endpoint is comparing Disease-Free Survival (DFS) in treatment group versus control group.

2. The secondary efficacy endpoints are

   • 5- and 10-year (disease free survival) DFS
   • 3-year overall survival (OS)
   • 5- and 10-year overall survival (OS), and Overall safety profile and adverse events (AEs)

Safety Assessments:

Patients will be assessed at every study visit for the safety endpoints AEs,vital signs, physical examinations and laboratory data; yearly follow-up of survival will include imaging studies, ECGs, MUGA or ECHO scans and concomitant medications.

• Biological: NeuVax vaccine
  E75 peptide acetate (HER2/neu p366-379) in Water for Injection (WFI, 1.5 mg/mL mixed with 250 microgram Leukine (sargramostim, GM-CSF), for intradermal injections administered once a month for six months, followed by booster inoculations administered once every six months for five additional injections.
  Other Name: E75 peptide acetate , WFI, sargramostim, GM-CSF
• Biological: Leukine (sargramostim, GM-CSF) and water for injection
  Leukine 250 microgram in water for injection, monthly intradermal injections for six months, followed by booster inoculations administered once every six months for five additional injections.
  Other Name: Leukine(R)

• Experimental: NeuVax vaccine
  NeuVax [E75 acetate in WFI solution with Leukine(R)(sargramostim,GM-CSF)
  Intervention: Biological: NeuVax vaccine
• Active Comparator: Control
  Control: Leukine(GM-CSF, sargramostim)with Water for injection
  Intervention: Biological: Leukine (sargramostim, GM-CSF) and water for injection

Key Inclusion Criteria:

• Women, 18 years of age and higher
• Pathological diagnosis of invasive adenocarcinoma of the breast
• Breast cancer completely excised
• Node-positive disease
• Primary tumor stage T1-3
• HER2 negative (HER2 1+ by IHC or HER2 2+ by IHC/FISH)
• HLA-A2 or HLA-A3 haplotype
• Completed NCCN approved neo-adjuvant/adjuvant chemotherapy or both
• Completed radiation therapy
• No evidence of disease

Key Exclusion Criteria:

• Bilateral breast malignancy or suspicious mass in opposite breast
• History of prior breast cancer, ductal carcinoma in situ.
• Prior trastuzumab therapy.
• New York Heart Association Stage 3 or 4 cardiac disease
• Sensory/motor neuropathy ≥ Grade 2.
• Autoimmune diseases or immune deficiency disease
• Patients on chronic steroid therapy, other immunosuppressive therapy