A Vaccine (Alpha-Lactalbumin) for the Treatment of Stage II-III Triple-Negative Breast Cancer

Inclusion Criteria

• TRIPLE NEGATIVE COHORT: Histologically proven invasive breast cancer.
• TRIPLE NEGATIVE COHORT: Primary tumor must be estrogen receptor (ER)-negative (ER in < 1% of cells), progesterone receptor (PR)-negative (PR in < 1% of cells), and HER2-negative (0-1+ by immunohistochemistry [IHC] or fluorescence in situ hybridization [FISH] ratio < 2.0 with signal number < 6/cell).
• TRIPLE NEGATIVE COHORT: Patients must be high risk, defined as either: * Pathologic stage IIA, IIB, IIIA, IIIB, or IIIC by American Joint Committee on Cancer (AJCC) 8, or * Residual invasive cancer in breast or regional nodes following preoperative chemotherapy
• TRIPLE NEGATIVE COHORT: Patients must have no convincing evidence of recurrent disease based on one of the following * Bone scan and imaging scans of the chest/abdomen/pelvis or * Fludeoxyglucose (FDG) positron emission tomography (PET) scan.
• TRIPLE NEGATIVE COHORT: >=1 months since last active therapy with chemotherapy (excluding Xeloda/capecitabine), radiation therapy, or surgery and at least 6 weeks of pembrolizumab therapy planned after the first dose of alpha-lactalbumin vaccine
• TRIPLE NEGATIVE COHORT: Treatment prior to enrollment must be consistent with National Comprehensive Cancer Network (NCCN) guidelines extant at the time treatment was given, found at: https://www.nccn.org/.
• TRIPLE NEGATIVE COHORT: Age >= 18 years.
• TRIPLE NEGATIVE COHORT: ECOG Performance Status 0-1.
• TRIPLE NEGATIVE COHORT: White blood count (WBC) >= 3,000/mcl.
• TRIPLE NEGATIVE COHORT: Hemoglobin >= 10.0 gm/dL.
• TRIPLE NEGATIVE COHORT: Platelets >= 100,000/mcL.
• TRIPLE NEGATIVE COHORT: Total bilirubin within normal limits.
• TRIPLE NEGATIVE COHORT: Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3 x upper limits of normal (ULN).
• TRIPLE NEGATIVE COHORT: Serum creatinine =< 1.5 x ULN.
• TRIPLE NEGATIVE COHORT: Serum prolactin level must be =< upper limits of normal (ULN).
• TRIPLE NEGATIVE COHORT: Subjects must have the ability to understand and the willingness to sign and provide a written informed consent document.
• TRIPLE NEGATIVE COHORT: Subjects must have archival tissue available for potential correlative studies (e.g., assays for α-lactalbumin expression or tumor infiltrating lymphocytes), but tumors will not be required to exhibit overexpression of alpha lactalbumin for enrollment.
• TRIPLE NEGATIVE COHORT: Subject agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection. Patients may be asked to complete a “wash out” period prior to the first dose of vaccine at the principal investigators (PI’s) discretion to ensure the absence of all alternative therapies
• PREVENTION COHORT: Participant must have a high risk for developing triple-negative breast cancer, defined as: carrying a deleterious mutation in BRCA1, PALB2 or BRCA2.
• PREVENTION COHORT: Patients must have no evidence of breast cancer based on both of the following: * Negative mammography or breast MRI within 180 days * Negative breast examination by a physician or advanced practice practitioner within 30 days.
• PREVENTION COHORT: Age > 18 years.
• PREVENTION COHORT: ECOG Performance Status 0-1.
• PREVENTION COHORT: WBC > 3,000/mcl.
• PREVENTION COHORT: Hemoglobin > 10.0 gm/dL.
• PREVENTION COHORT: Platelets > 100,000/mcL.
• PREVENTION COHORT: Total bilirubin within normal limits.
• PREVENTION COHORT: ALT/AST < 3 x upper limits of normal (ULN).
• PREVENTION COHORT: Serum creatinine < 1.5 x ULN.
• PREVENTION COHORT: Serum prolactin level must be < upper limits of normal (ULN).
• PREVENTION COHORT: Subjects must have the ability to understand and the willingness to sign and provide a written informed consent document.
• PREVENTION COHORT: Subject agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection. Patients may be asked to complete a “wash out” period prior to the first dose of vaccine at the PI’s discretion to ensure the absence of all alternative therapies.
• PEMBROLIZUMAB COHORT: Histologically proven invasive breast cancer.
• PEMBROLIZUMAB COHORT: Primary tumor must be ER-negative (ER in < 1% of cells), PR-negative (PR in < 1% of cells), and HER2-negative (0-1+ by IHC or FISH ratio < 2.0 with signal number <6/cell), or consistent with contemporary NCCN guidelines.
• PEMBROLIZUMAB COHORT: Patients must be high risk, defined as having residual invasive cancer in breast or regional nodes following pre-operative chemotherapy.
• PEMBROLIZUMAB COHORT: Patients must have no convincing evidence of recurrent disease based on one of the following: * Bone scan and imaging scans of the chest/abdomen/pelvis or * FDG PET scan.
• PEMBROLIZUMAB COHORT: >= 1 months since last active therapy with chemotherapy (excluding xeloda/capecitabine), radiation therapy, or surgery and at least 6 weeks of pembrolizumab therapy planned after the first dose of alpha-lactalbumin vaccine.
• PEMBROLIZUMAB COHORT: Treatment prior to enrollment must be consistent with NCCN guidelines extant at the time treatment was given.
• PEMBROLIZUMAB COHORT: Age >= 18 years.
• PEMBROLIZUMAB COHORT: ECOG performance status 0 - 1.
• PEMBROLIZUMAB COHORT: WBC >= 3,000/mcl.
• PEMBROLIZUMAB COHORT: Hemoglobin >= 10.0 gm/dL.
• PEMBROLIZUMAB COHORT: Platelets >= 100,000/mcL.
• PEMBROLIZUMAB COHORT: Total bilirubin within normal limits.
• PEMBROLIZUMAB COHORT: ALT/AST < 3 x upper limits of normal (ULN).
• PEMBROLIZUMAB COHORT: Serum creatinine =< 1.5 x ULN.
• PEMBROLIZUMAB COHORT: Serum prolactin level must be =< upper limits of normal (ULN).
• PEMBROLIZUMAB COHORT: Subjects must have the ability to understand and the willingness to sign and provide a written informed consent document.
• PEMBROLIZUMAB COHORT: Subjects must have archival tissue available for potential correlative studies (e.g., assays for alpha-lactalbumin expression or tumor infiltrating lymphocytes), but tumors will not be required to exhibit overexpression of α-lactalbumin for enrollment.
• PEMBROLIZUMAB COHORT: Subject agrees not to use alternative therapies from the time of informed consent through 30 days following the last vaccine injection. Patients may be asked to complete a “wash out” period prior to the first dose of vaccine at the PI’s discretion to ensure the absence of all alternative therapies.

Exclusion Criteria

• TRIPLE NEGATIVE COHORT: Receipt of cytotoxic chemotherapy within 4 weeks of study entry (except for capecitabine in subjects enrolled in the pembrolizumab cohort).
• TRIPLE NEGATIVE COHORT: Radiation therapy within 4 weeks of study entry.
• TRIPLE NEGATIVE COHORT: Failure to recover from the toxicity of the previous therapy to Common Terminology Criteria for Adverse Events (CTCAE) grade 0-1, except for alopecia and grade 2 neuropathy.
• TRIPLE NEGATIVE COHORT: Need for systemic corticosteroid use (except as physiologic replacement, defined as prednisone 10 mg/day or equivalent).
• TRIPLE NEGATIVE COHORT: Need for immunosuppression (e.g., for a history of organ transplantation).
• TRIPLE NEGATIVE COHORT: Known human immunodeficiency virus (HIV) infection.
• TRIPLE NEGATIVE COHORT: Active or planned lactation or pregnancy.
• TRIPLE NEGATIVE COHORT: Patients taking or planning to take oral contraceptives will be excluded, as there is some evidence that such agents can induce lactational foci. This includes patients using hormone containing intrauterine device (IUD)’s.
• TRIPLE NEGATIVE COHORT: Refusal to use effective non-hormonal contraception. Acceptable contraception methods include but may not be limited to barrier contraception (diaphragm or condom), non-hormonal intrauterine device, vasectomy of male partner.
• TRIPLE NEGATIVE COHORT: Subjects receiving any other investigational agents within the last 4 weeks.
• TRIPLE NEGATIVE COHORT: Subjects with any known recurrence or metastasis.
• TRIPLE NEGATIVE COHORT: Subjects with a history of another active invasive malignancy within 5 years of study entry.
• TRIPLE NEGATIVE COHORT: History of allergic reactions to alpha-lactalbumin, human milk (excluding lactose intolerance), Zymosan, or other agents used in this study.
• TRIPLE NEGATIVE COHORT: Subjects with 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.
• TRIPLE NEGATIVE COHORT: Subjects with known hyperprolactinemia.
• TRIPLE NEGATIVE COHORT: Subjects being treated with drugs known to cause hyperprolactinemia.
• TRIPLE NEGATIVE COHORT: Subjects diagnosed with TNBC while pregnant
• TRIPLE NEGATIVE COHORT: Subjects having lactated within 6 months of study start (first dose of vaccine)
• PREVENTION COHORT: Receipt of cytotoxic chemotherapy within 4 weeks of study entry (including for benign indications).
• PREVENTION COHORT: Radiation therapy within 4 weeks of study entry (including for benign indications).
• PREVENTION COHORT: Need for systemic corticosteroid use (except as physiologic replacement, defined as prednisone 10 mg/day or equivalent).
• PREVENTION COHORT: Need for immunosuppression (e.g., for a history of organ transplantation).
• PREVENTION COHORT: Known HIV infection.
• PREVENTION COHORT: Active or planned lactation or pregnancy.
• PREVENTION COHORT: Patients taking or planning to take oral contraceptives will be excluded, as there is some evidence that such agents can induce lactational foci. This includes patients using hormone containing IUD’s.
• PREVENTION COHORT: Refusal to use effective non-hormonal contraception. Acceptable contraception methods include but may not be limited to barrier contraception (diaphragm or condom), non-hormonal intrauterine device, vasectomy of male partner.
• PREVENTION COHORT: Subjects receiving any other investigational agents within the last 4 weeks.
• PREVENTION COHORT: Subjects with a history of invasive malignancy within 5 years of study entry.
• PREVENTION COHORT: History of allergic reactions to alpha-lactalbumin, human milk (excluding lactose intolerance), zymosan, or other agents used in this study.
• PREVENTION COHORT: Subjects with 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.
• PREVENTION COHORT: Subjects with known hyperprolactinemia.
• PREVENTION COHORT: Subjects being treated with drugs known to cause hyperprolactinemia.
• PREVENTION COHORT: Members of all races and ethnic groups will be eligible for this trial. Bilateral prophylactic mastectomy is not standard of care for men at genetic risk for breast cancer, so men are not anticipated to be enrolled in this cohort.
• PREVENTION COHORT: Subjects having lactated within 6 months of study start (first dose of vaccine)
• PEMBROLIZUMAB COHORT: All exclusion criteria for the pembrolizumab cohort will be the same as the TNBC cohort, unless noted otherwise.