Phase I Trial of Adjuvant Therapy With an Alpha-lactalbumin Vaccine in Patients With Non-Metastatic Triple-Negative Breast Cancer at High Risk of Recurrence

CASE6119

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.

2021-10-01

2024-11-01

2025-03-01

Recruiting

Early phase I

45

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.

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2024-05-16