PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer

Inclusion Criteria

• •Willing and able to provide written informed consent for the study.
• •Female aged ≥18 years on the day of signing informed consent.
• •HLA A2+ by deoxyribonucleic acid (DNA) sequence analysis (by history with documentation or as part of this study).
• •Histopathological diagnosis of metastatic or inoperable locally advanced TNBC that meets the following criteria:
• •--Triple negative defined as Estrogen Receptor (ER)\<1%, Progesterone Receptor (PR)\<1%, and Human Epidermal Growth Factor Receptor 2 (HER2) negative according to American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines by local testing according to institutional standards.
• •For tumors with equivocal interpretation of receptor status (e.g., ER/PR ≥1% "weak" or "faint" staining), the Principal Investigator will have final determination of triple-negative status. For tumors with discrepant receptor results between 2 or more biopsies (including metastatic and/or early stage biopsies), the Principal Investigator will have final determination of triple negative status, but in general the most recent biopsy can be used for eligibility purposes. If receptor testing is not available on a metastatic biopsy, the primary tumor test result is acceptable.
• •Metastatic or inoperable locally advanced disease is defined as either: histologically confirmed metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the opinion of the treating physician, is not amenable to curative intent surgical resection; or, radiological or clinical evidence suggestive and supportive of metastatic disease without a documented metastatic biopsy, provided the patient has a prior diagnosis of TNBC that otherwise meets the eligibility criteria.
• •--Ductal, lobular, mixed, or metaplastic histology.
• •Measurable disease, as determined by RECIST 1.1.
• •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix section 16.1)
• •At least one line of prior systemic therapy for metastatic or recurrent breast cancer (there is no limit to the number of prior therapies).
• •Adequate normal organ and marrow function within 10 days of planned treatment initiation, as defined below:
• •Hematologic
• •Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
• •Absolute neutrophil count (ANC) ≥1.5x10\^9/L (≥1500 per mm3)
• •Platelet count ≥100x109/L (≥100,000 per mm3) Renal
• •Serum creatinine ≤1.5 x the upper limit of normal (ULN) OR measured or calculated creatinine clearance ≥60 mL/min for patients with creatinine levels \>1.5 x institutional Upper Limit of Normal (ULN) (calculated per institutional standard). (Glomerular filtration rate can be used in place of creatinine or creatinine clearance.) Hepatic
• •Serum bilirubin ≤1.5 x institutional ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels \>1.5 x ULN
• •Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 x institutional ULN OR ≤5 x ULN for patients with known liver metastases.
• •Albumin ≥2.5 mg/dL Coagulation
• •International normalized ratio (INR) or prothrombin time (PT) ≤1.5 x ULN, unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
• •Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants Other
• •Lactate Dehydrogenase (LDH) ≤1.5 x institutional ULN
• •* Willing to provide archived tissue for correlative studies. If no archived sample is available the patient will still be eligible.
• •* Negative virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B surface antigen (HBsAg), and hepatitis C virus (HCV) DNA.
• •* Either of non-reproductive potential (i.e., post-menopausal by history of age ≥50 years old and no menses for ≥1 year without an alternative medical cause; OR history of hysterectomy, history of bilateral tubal ligation, or history of bilateral oophorectomy) OR must have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• •* If of childbearing potential (i.e., does not meet criteria for non-reproductive potential above), willing to use 2 methods of birth control, or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study treatment
• •* Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations, including follow-up