A Double-blind, Randomized Trial of Active Immunotherapy With Globo H-KLH (OPT-822) in Subjects With Metastatic Breast Cancer

Inclusion Criteria:

- Female subjects ≥ 21 years of age with histological or cytological diagnosis of
breast carcinoma.

- Subjects with metastatic breast cancer who have achieved stable disease (SD), partial
response (PR), or complete response (CR) after at least 1 regimen of anticancer
therapy (i.e. chemotherapy or target therapy, either alone or in any combination).
Involvement of supraclavicular lymph node is considered metastasis.

- Subjects must have recovered from toxicities of prior therapies. (i.e. CTCAE ≤ grade
2).

- Performance status: ECOG ≤ 1 and life expectancy ≥ 3 months.

- Organ Function Requirements - Subjects must have adequate organ functions as defined
below:

- AST/ALT ≤ 3X ULN (upper limit of normal)

- AST/ALT ≤ 5X ULN [with underlying Liver Metastasis]

- Total Bilirubin ≤ 2.0 X ULN

- Serum Creatinine ≤ 1.5X ULN

- ANC ≥ 1500 /μL

- Platelets > 100,000/μL

- No Symptomatic Congestive Heart Failure (Ejection Fraction EF ≥ 50%)

- Ability to understand and the willingness to sign a written informed consent document
according to institutional guidelines.

- All positive or negative ER (estrogen receptor), PR (progesterone receptor), and
HER-2 subjects are eligible for this study.

- However, subjects who are HER-2 positive and responsive to anti-HER-2 therapy (e.g.
Herceptin), are encouraged to remain on anti-HER-2 therapy and not enroll in this
trial.

- Subjects who desire to enroll in this study and for whom anti-HER-2 therapy is not
available or contraindicated, may be eligible to enroll in this trial.

- In countries where continuous anti-HER2 therapy is considered standard of care for
HER-2 positive metastatic disease, HER-2 positive subjects are not eligible.

- Women of childbearing potential must be willing to implement adequate contraception
during the study. An adequate method of contraception will be at the investigator's
discretion.

Exclusion Criteria:

- Subjects are pregnant or breast-feeding at entry.

- Subjects with more than 2 events of disease progression after the development of
metastatic breast cancer.

- Subjects who are currently receiving any other concomitant anticancer therapy with
the EXCEPTION of bisphosphonates and hormone therapy.

- During the study period, subjects using hormonal therapy and bisphosphonates
should maintain a constant dose and should not change existing regimen.

- However, if a change in hormonal therapy is indicated, e.g. due to intolerable
adverse effects, the regimen may be modified but change should be minimized
thereafter.

- Subjects with metastasis limited to the bone only are excluded. However, subjects
with current metastasis limited to the bone only and with a history of distant
metastasis are eligible. Subjects with current metastasis limited to the bone only
and with current breast tissue lesion are eligible.

- Subjects who have any history of other malignancy (except non-melanoma skin carcinoma
and carcinoma-in-situ of the uterine cervix) within 5 years of study entry.

- Subjects with splenectomy.

- Subjects with HIV infection.

- Subjects with any major autoimmune diseases or autoimmune disorders requiring
systemic iv/oral steroids or immunosuppressive or immunomodulatory therapies.

- e.g. Type 1 juvenile onset diabetes mellitus, antibody positive for rheumatoid
arthritis, Grave's disease, Hashimoto's thyroiditis, lupus, scleroderma,
systemic vasculitis, hemolytic anemia, immune mediated thrombocytopenia, etc

- Autoimmune disorders confined to the skin (e.g. psoriasis) are eligible, and
topical steroids are allowed for the treatment of such skin disorders.

- Subjects with any known uncontrolled inter-current illness including ongoing or
active infections, symptomatic congestive heart failure, unstable angina pectoris,
cardiac arrhythmia, or psychiatric illness/social situations that would limit
compliance with study requirements.

- Subjects with any of the following MEDICATIONS within 4 weeks prior to randomization:

- Anti-neoplastic agents

- Immunotherapy [mAbs, Interferons, Cytokines (except GCSF)]

- Immunosuppressants (e.g. Cyclosporin, Rapamycin, Tacrolimus, Rituximab,
Alemtuzumab, Natalizumab, etc.).

- Another investigational drug

- Subjects with pleural effusions and/or ascites, due to malignancy, requiring
paracentesis every 2 weeks or more frequently.

- Subjects with any known severe allergies (e.g. anaphylaxis) to any active or inactive
ingredients in the study drugs.

- Subjects with bladder inflammation and urinary outflow obstruction.