SHS_492268 KAPH CCAN 14177

Combination immunotherapy with Herceptin and the HER2 vaccine E75 in low and intermediate HER2 negative expressing breast cancer patients to prevent recurrence

The study will be a multi-center, prospective, randomized, single-blinded, placebo-controlled Phase II trial of Herceptin + NeuVax(TM) vaccine (E75 peptide/granulocyte macrophage-colony stimulating factor) (GM-CSF) versus Herceptin + GM-CSF alone. The target study population is node-positive (NP) (or node-negative [NN] if negative for both ER and PR) breast cancer patients with HER2 1+ and 2+ expressing tumors who are disease-free after standard of care therapy. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA-typed. E75 is a CD8-eliciting peptide vaccine that is restricted to HLA-A2+ or HLA-A3+ patients (approximately two-thirds of the US population).

Patients will be included in the study based on the following criteria:

Node-positive breast cancer (AJCC N1, N2, or N3)
Node-negative breast cancer if negative for both estrogen (ER) and progesterone (PR) receptors and have received chemotherapy as standard of care
Clinically cancer-free (no evidence of disease) after standard of care therapy (surgery, chemotherapy, radiation therapy as directed by NCCN guidelines). Hormonal therapy will continue per standard of care. Neoadjuvant chemotherapy is allowed.
HER2 expression of 1+ or 2+ by IHC. FISH or Dual-ISH testing must be performed on IHC 2+ tumors and shown to be non-amplified by FISH (≤2.0) or by Dual-ISH (≤2.0).
HLA-A2, A3, A24, or A26 positive
Must start study treatment (receive first Herceptin infusion) 15between 3-12 weeks from completion of standard of care therapy

Patients will be excluded from the study based on the following criteria:

Node-negative breast cancer (AJCC N0 or N0(i+)) unless negative for both estrogen (ER) and progesterone (PR) receptors and has received chemotherapy as standard of care
Clinical or radiographic evidence of distant or residual breast cancer
HER2 negative (IHC 0) or HER2 3+ or FISHDual-ISH amplified (FISH >2.0); Dual-ISH >2.0
HLA-A2, A3, A24, A26 negative
History of prior Herceptin therapy
NYHA stage 3 or 4 cardiac disease
Immune deficiency disease or HIV, HBV, HCV
Receiving immunosuppressive therapy including chemotherapy, chronic steroids, methotrexate, or other known immunosuppressive agents
Tbili >1.8, creatinine>2, hemoglobin<10, platelets<50,000, WBC<2,000
Phase II
Henry Kaplan, M.D.
Cancer Insight, LLC
Casey Daniels
  • Swedish Medical Center