Overview

The purpose of this study is to determine the safety as well as the most effective dose of the alpha-lactalbumin vaccine (aLA breast cancer vaccine) to treat patients with non-metastatic triple negative breast cancer, participants who are of cancer-free but may be at risk for triple-negative breast cancer, and for participants who are receiving adjuvant pembrolizumab following initial triple negative breast cancer treatment.

Eligibility

Inclusion Criteria:

Triple Negative Cohort:

• Histologically proven invasive breast cancer.
• 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 (https://www.nccn.org/).
• Patients must be high risk, defined as either:
• Pathologic stage IIA, IIB, IIIA, IIIB, or IIIC by AJCC 8, or
• Residual invasive cancer in breast or regional nodes following preoperative chemotherapy.
• 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.
• ≥1 months since last active therapy (chemotherapy, radiation therapy, or surgery) and ≤ 36 months since the initiation of treatment for the current cancer, based on the period of highest risk for patients with Stages I-III triplenegative breast cancer [33, 34].
• Treatment prior to enrollment must be consistent with NCCN guidelines extant at the time treatment was given, found at: https://www.nccn.org/.
• Age greater than or equal to 18 years.
• ECOG Performance Status 0-1.
• Adequate major organ function, defined as:

        WBC ≥ 3,000/mcl, hemoglobin ≥ 10.0 gm/dL, platelets ≥ 100,000/mcL, total bilirubin within
        normal limits, ALT/AST <3 x upper limits of normal (ULN), serum creatinine ≤ 1.5 x ULN.
          -  Serum prolactin level must be ≤ upper limits of normal (ULN).
          -  Subjects must have the ability to understand and the willingness to sign and provide a
             written informed consent document.
          -  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 α-lactalbumin for enrollment.
          -  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.
        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
          -  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
          -  Age ≥ 18 years
          -  ECOG Performance Status 0-1.
          -  Adequate major organ function, defined as: WBC ≥ 3,000/mcl, hemoglobin ≥ 10.0 gm/dL,
             platelets >100,000/mcL, total bilirubin within normal limits, ALT/AST <3 x upper
             limits of normal (ULN), serum creatinine ≤ 1.5 x ULN.
          -  Serum prolactin level must be ≤ upper limits of normal (ULN)
          -  Subjects must have the ability to understand and the willingness to sign and provide a
             written informed consent document.
          -  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.
          -  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 (https://www.nccn.org/).
          -  Patients must be high risk, defined as having residual invasive cancer in breast or
             regional nodes following pre-operative chemotherapy.
          -  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.
          -  >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.
          -  Treatment prior to enrollment must be consistent with NCCN guidelines extant at the
             time treatment was given, found at: https://www.nccn.org/.
          -  Age >18 years.
          -  ECOG Performance Status 0-1.
          -  Adequate major organ function, defined as: WBC > 3,000/mcl, hemoglobin > 10.0 gm/dL,
             platelets > 100,000/mcL, total bilirubin within normal limits, ALT/AST <3 x upper
             limits of normal (ULN), serum creatinine < 1.5 x ULN.
          -  Serum prolactin level must be < upper limits of normal (ULN).
          -  Subjects must have the ability to understand and the willingness to sign and provide a
             written informed consent document.
          -  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 α-lactalbumin for enrollment.
          -  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).
          -  Radiation therapy within 4 weeks of study entry.
          -  Failure to recover from the toxicity of the previous therapy to CTCAE Grade 0-1,
             except for alopecia and grade 2 neuropathy.
          -  Need for systemic corticosteroid use (except as physiologic replacement, defined as
             prednisone 10 mg/day or equivalent).
          -  Need for immunosuppression (e.g., for a history of organ transplantation).
          -  Known HIV infection.
          -  Active or planned lactation or pregnancy.
          -  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.
          -  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.
          -  Subjects receiving any other investigational agents within the last 4 weeks.
          -  Subjects with any known recurrence or metastasis.
          -  Subjects with a history of another active invasive malignancy within 5 years of study
             entry.
          -  History of allergic reactions to α-lactalbumin, human milk (excluding lactose
             intolerance), zymosan, or other agents used in this study.
          -  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.
          -  Subjects with known hyperprolactinemia.
          -  Subjects being treated with drugs known to cause hyperprolactinemia
        Prevention Cohort:
          -  Receipt of cytotoxic chemotherapy within 4 weeks of study entry (including for benign
             indications).
          -  Radiation therapy within 4 weeks of study entry (including for benign indications)
          -  Need for systemic corticosteroid use (except as physiologic replacement, defined as
             prednisone 10 mg/day or equivalent).
          -  Need for immunosuppression (e.g., for a history of organ transplantation).
          -  Known HIV infection.
          -  Active or planned lactation or pregnancy.
          -  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.
          -  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.
          -  Subjects receiving any other investigational agents within the last 4 weeks.
          -  Subjects with a history of invasive malignancy within 5 years of study entry.
          -  History of allergic reactions to α-lactalbumin, human milk (excluding lactose
             intolerance), zymosan, or other agents used in this study.
          -  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
          -  Subjects with known hyperprolactinemia
          -  Subjects being treated with drugs known to cause hyperprolactinemia
        Pembrolizumab Cohort:
        -All exclusion criteria for the pembrolizumab cohort will be the same as the TNBC cohort as
        outlined above, unless noted otherwise.