A Phase 3, Randomized, Open-Label Study of the Anti-Globo H Vaccine Adagloxad Simolenin (OBI-822)/OBI-821 in the Adjuvant Treatment of Patients with High-Risk, Early-Stage Globo H-Positive Triple Negative Breast Cancer.

Inclusion Criteria

- Documented radiographic and histopathologic confirmed primary localized invasive

breast cancer.

- Histologically documented TNBC (estrogen receptor negative [ER-]/progesterone receptor

negative [PR-]/human epidermal growth factor 2 negative [HER2-]) defined as

ER-negative and PR-negative (≤5% positive cells stain by IHC for both ER and PR), and

negative HER2/neu- status, confirmed on tumor sample.

- HER2/neu negative will be defined as one of the following criteria:

- IHC 0 or 1+

- Single-probe average HER2 gene copy number of <6 signals/nucleus

- Dual-probe fluorescent in-situ hybridization (FISH) HER2/neu chromosome 17

(CEP17) non-amplified ratio of <2

- Globo H IHC H-score ≥15 from the residual primary site/or lymph node (if primary site

is not available) tumor obtained at time of definitive surgery. Globo H expression

will be determined during pre-screening by Central lab. Instructions for submission of

slides/tumor tissue blocks are provided in the protocol and study Lab Manual.

- No evidence of metastatic disease in chest, abdomen and pelvis by CT or other adequate

imagining during the Screening Phase. Imaging within 3 months prior to randomization

is acceptable as baseline scan. Bone scans and imaging of the brain at screening is

optional, and should be symptom directed.

- High risk patients with no evidence of disease after completing standard treatment and

meeting ONE of the following criteria:

- Neoadjuvant chemotherapy followed by definitive surgery: Residual invasive

disease following neoadjuvant chemotherapy defined as: A contiguous focus of

residual invasive cancer in the surgical breast measuring ≥1 cm in diameter

and/or with residual invasive cancer in at least one axillary node

(micrometastases or macrometastases), as determined by local pathology review.

- Definitive surgery followed by adjuvant chemotherapy: Pathological Stage IIB,

Stage IIIA , Stage IIIB, or Stage IIIC disease according to the 8th edition of

the American Joint Committee on Cancer (AJCC) Cancer Staging Manual.

- Must have completed a standard taxane, and/or anthracycline-based multi-agent

chemotherapy regimen either in the neoadjuvant or adjuvant setting (e.g., National

Comprehensive Cancer Network recommended regimens):.

- At least 4 cycles of a standard multi-agent chemotherapy regimen must have been

received, unless precluded by toxicities

- Post operative adjuvant capecitabine or a platinum monotherapy in patients with

residual disease after neoadjuvant chemotherapy is allowed.

- Randomization must occur within 12 weeks after completion of standard of care

treatment (surgery and/or chemotherapy) and within 46 weeks from the date of

definitive surgery. Note: patients receiving adjuvant capecitabine or platinum

monotherapy after neoadjuvant multi-agent chemotherapy may be randomized and initiate

study treatment during (or within 12 weeks after completion of) the adjuvant

capecitabine or platinum monotherapy.

- All treatment-related toxicities resolved to Grade <1 on National cancer institute

Common Terminology Criteria for Adverse Events (NCI-CTCAE version 5.0) criteria

(except hair loss and ≤Grade 2 neuropathy, which are acceptable).

- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

- Females must be either of non-childbearing potential, i.e., surgically sterilized

(have documented sterilization, bilateral oophorectomy/salpingectomy at least 3 months

before the start of the trial and/or hysterectomy), or one year postmenopausal; or if

of childbearing potential must have a negative pregnancy test (urine or serum) at

randomization.

- Males and females of childbearing potential and their partners must be willing to use

effective contraception during the entire Treatment Phase period and for at least 4

weeks (28 days) after the last dose of study treatment.

- Adequate hematological, hepatic and renal function as defined below:

- Absolute neutrophil count (ANC) ≥1,500/µL

- Platelets ≥75,000/µL

- Hemoglobin ≥8.5g/dL

- Serum creatinine ≤1.5 × upper limit of normal (ULN) or calculated creatinine

clearance ≥55 mL/min for subjects with creatinine levels >1.5 × institutional ULN

(glomerular filtration rate can also be used in place of creatinine or creatinine

clearance may be calculated per institutional standard)

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × ULN

- Alkaline Phosphatase (ALP) ≤2.5 × ULN

- Serum total bilirubin ≤1.5 × ULN (unless Gilbert's disease is documented)

- Consent to participate with a signed and dated Institutional Review Board

(IRB)/Independent Ethics Committee (IEC) approved patient informed consent for the

study prior to beginning any specific study procedures.

- Ability to understand and willingness to complete all protocol required procedures.

Exclusion Criteria

- Local recurrence of or previous history of ipsilateral or contralateral invasive

breast cancer within 10 years prior to randomization.

- Definitive clinical or radiologic evidence of metastatic disease

- Synchronous bilateral breast cancer, unless both tumors are confirmed as TNBC.

- Have received any post-operative immunotherapy with antigen, antibody, immune

checkpoint inhibitors (Programmed cell death-1 [PD-1]/ Programmed cell

death-ligand-1inhibitors [PD-L-1], anti-cytotoxic T lymphocyte associated protein 4

[CTLA 4] therapy), or other anti-cancer vaccines (neoadjuvant receipt of immune

checkpoint inhibitors will not be exclusionary if the patient meets all other

eligibility criteria).

- Concomitant treatment with approved anticancer therapy or immunotherapy including

checkpoint inhibitors (e.g. PD-1 inhibitors) or other investigational therapy, if

expected during the study. Adjuvant capecitabine or platinum monotherapy is allowed

during the study.

- A history of other malignancies (except non melanoma skin carcinoma, carcinoma in situ

of the uterine cervix, follicular or papillary thyroid cancer) within 5 years prior to

randomization.

- Have any active autoimmune disease or disorder that requires systemic

immunosuppressive/immunomodulatory therapy. NOTE: Autoimmune diseases that are

confined to the skin (e.g., psoriasis) that can be treated with topical steroids alone

are allowed during the study.

- Oral/parenteral corticosteroid treatment (>5 mg/day of prednisone/equivalent), within

2 weeks prior to randomization or anytime during the study. NOTE: inhaled steroids for

treatment of asthma; and topical steroids are allowed during the study.

- Any known uncontrolled concurrent illness that would limit compliance with study

requirements, including but not limited to ongoing or active infections, symptomatic

congestive heart failure, unstable angina pectoris, cardiac arrhythmia, psychiatric

disorders, or substance abuse.

- Any known hypersensitivity to active/inactive ingredients in the study drug

formulation or known severe allergy or anaphylaxis to fusion proteins.

- Prior receipt of a glycoconjugate vaccine for cancer immunotherapy.

- Known history or positive for human immunodeficiency virus (HIV positive), unless on

effective anti-retroviral therapy with undetectable viral load within 6 months of

therapy (note: HIV testing not required for study entry).

- Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection prior to

randomization. Patients who have completed curative therapy for HCV are eligible. For

patients with evidence of chronic HBV infection, the HBV viral load must be

undetectable on suppressive therapy. (note: HBV/HCV testing is not required for study

entry).

- Any condition, including significant diseases and/or laboratory abnormalities that

would place the patient at unacceptable risk for study participation.

- Currently pregnant or breastfeeding women.

- Currently participating in or has participated in a breast cancer therapeutic clinical

trial within 4 weeks (24 days) prior to randomization.