Nelipepimut-S Plus GM-CSF Vaccine Therapy in Treating Patients With Breast Cancer

PRIMARY OBJECTIVES:

I. Evaluate for nelipepimut-S-specific cytotoxic T lymphocyte (CTL; cluster of
differentiation [CD]8+ T cell) response in patients receiving NeuVax (nelipepimut-S plus
GM-CSF [sargramostim]) compared to patients receiving GM-CSF alone (control).

SECONDARY OBJECTIVES:

I. Toxicity profile and frequency of adverse events in women with ductal carcinoma in situ
(DCIS) of the breast receiving nelipepimut-S vaccine as compared to women receiving GM-CSF
alone.

II. Immune response to other tumor antigens (epitope spreading). III. Functional capacity of
the immune response to vaccination. IV. Determine CTL functional capability using
intracellular cytokine assays. V. Evaluate polyfunctional cytokine responses assessed by
multiplex assay. VI. Presence of DCIS at resection. VII. Difference in human epidermal growth
factor receptor 2 (HER2) expression in the biopsy and the surgical specimen excised
post-vaccination.

VIII. Histologic responses: degree of lymphocyte infiltration determined on hematoxylin and
eosin (H&E) stained slides and by immunohistochemistry staining for CD3, CD4 and CD8.

IX. Histologic responses: Ki67 in DCIS cells (proliferation). X. Cleaved caspase 3 in DCIS
cells (apoptosis). XI. Immune infiltrates in normal tissue maximally distant from the tumor
(in mastectomy samples).

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive nelipepimut-S plus GM-CSF vaccine intradermally (ID) 2 vaccination 2
weeks apart prior to surgery.

ARM II: Patients receive sargramostim ID 2 vaccinations 2 weeks apart prior to surgery, and 3
vaccinations 1 months apart post-surgery.

After completion of study treatment, patients are followed up at 1 and 3 months.

Inclusion Criteria:

- Participants must be pre- or post-menopausal

- Participants must have a diagnosis of DCIS made by core needle biopsy

- Participants must be human leukocyte antigen (HLA)-A2 positive

- Eastern Cooperative Oncology Group (ECOG) performance status must be 0 or 1 (Karnofsky
>= 60%)

- Platelets >= 100,000/mm^3

- Hemoglobin >= 10 g/dL

- Blood urea nitrogen < 2 x upper limit of normal (ULN)

- Alkaline phosphatase < 2 x ULN

- Lactate dehydrogenase < 2 x ULN

- Creatinine < 2 x ULN

- Bilirubin < 2 x ULN

- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
[SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
< 2 x ULN

- A normal ejection fraction, as defined by the participant's institution; only limited
echocardiograms (ECHOs) will be used as cardiac evaluation; no other tests are
allowed; ECHO is to be done only in HLA-A2 positive participants; If ECHO has been
done within 30 days prior to randomization and results showing a normal ejection
fraction have been obtained prior to randomization, an additional ECHO is not needed
at baseline

- Willingness to comply with all study interventions and follow-up procedures

- The ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

- Invasive breast cancer; areas of microinvasion or suspicious for microinvasion on the
core biopsy is allowed

- History of prior breast cancer treated within the past two years; patients completing
all breast cancer-specific treatment over two years prior to the current diagnosis are
eligible

- History of prior ductal carcinoma in situ (DCIS) treated within the past two years;
patients completing all treatment for a previous diagnosis of DCIS over two years
prior to the current diagnosis are eligible

- Prior lobular carcinoma in situ (LCIS) is allowed

- Pregnant, unwilling to use adequate contraception during study treatment duration or
breastfeeding; pregnant women will be excluded; all heterosexually active women who
may become pregnant must agree to use adequate contraception (hormonal or barrier
method of birth control; abstinence) prior to study entry and for the duration of
study participation OR be post-menopausal defined as any one of the following 1) prior
hysterectomy, 2) absence of menstrual period for 1 year in the absence of prior
chemotherapy or 3) absence of menstrual period for 2 years in women with a prior
history of chemotherapy exposure who were pre-menopausal prior to chemotherapy; should
a woman become pregnant or suspect she is pregnant while participating in this study,
she should inform her study physician immediately

- Any autoimmune disease or other medical condition that, in the opinion of the
investigator, would compromise the subject's safety

- Immune deficiency diseases such as immunoglobulin deficiency or immunosuppressive
therapy that might interfere with appropriate immune response

- Known history of or known active infection with human immunodeficiency virus (HIV),
hepatitis B or hepatitis C

- Patients on chronic steroid therapy or other immunosuppressive therapy except for
topical or inhaled steroids known to have low systemic absorption

- Patients with a known hypersensitivity to GM-CSF, yeast-derived products, or any
component of the GM-CSF product (e.g., mannitol)

- Concurrent treatment with other investigational agent

- History of non-breast malignancy within 5 years prior to randomization, except
curatively treated superficial bladder cancer, carcinoma in situ of the cervix (stage
0-1), and basal cell or squamous cell carcinoma of the skin

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to NeuVax

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
arrhythmia, or psychiatric illness/social situations that would limit compliance with
study requirements

- No recent or planned immunotherapy