Vaccine Therapy (INO-5401 with or without INO-9012) Followed by Electroporation in Adult Cancer and Non-cancer Patients with BRCA1 or BRCA2 Mutations

Inclusion Criteria

• COHORT A: Signed and dated written Institutional Review Board (IRB) approved informed consent
• COHORT A: Females or males aged >= 18 years
• COHORT A: Documented carrier of a pathogenic or likely pathogenic mutation in BRCA1 or BRCA2
• COHORT A: Diagnosis of invasive breast cancer, invasive ovarian cancer, pancreatic cancer (apart from neuroendocrine) or prostate cancer with completion of adjuvant therapy (other than hormonal therapy) and no clinical evidence of disease according to standard of care
• COHORT A: Minimum of two clear sites on the skin to allow for injection. Sites must be without tattoos, scars, or active lesions/rashes within 2 cm of intended injection site
• COHORT A: ECOG (Eastern Cooperative Oncology Group) performance status of 0
• COHORT A: Normal electrocardiogram (ECG) or ECG without clinically significant findings and which does not require clinical action
• COHORT A: ANC (absolute neutrophil count) >= 1.5x10^9 cell/ml (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Platelets >= 150,000 /mm^3 (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Hemoglobin >= 11.0 g/dL (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of total serum bilirubin (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of aspartate aminotransferase (AST) (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of alanine aminotransferase (ALT) (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of creatine phosphokinase (CPK) (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of alkaline phosphatase (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of serum creatinine (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Normal concentrations of prothrombin time (PT)-international normalized ratio (INR)/partial thromboplastin time (PTT) (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT A: Females who are post-menopausal only, which includes those who have had a hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; no menses for at least 12 months without an alternative medical cause; or a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) in women not using hormonal contraception or hormonal replacement therapy
• COHORT A: Male subjects with reproductive potential must be willing to use a condom with female partners of reproductive potential and their female sexual partners should use an additional highly effective method birth control (e.g. oral contraception and barrier methods, spermicide, and/or intrauterine device [IUD]). This requirement should be followed from screening through 24 weeks after last dose of immunotherapy
• COHORT A: Able and willing to comply with all study procedures
• COHORT B: Signed and dated written IRB approved informed consent
• COHORT B: Females or males aged >= 18 years
• COHORT B: Documented carrier of a pathogenic or likely pathogenic mutation in BRCA1 or BRCA2
• COHORT B: With or without prior prophylactic (but not therapeutic) mastectomy or salpingo-oophorectomy
• COHORT B: Minimum of two clear sites on the skin to allow for injection. Sites must be without tattoos, scars, or active lesions/rashes within 2 cm of intended injection site
• COHORT B: ECOG (Eastern Cooperative Oncology Group) performance status of 0
• COHORT B: Normal ECG or ECG without clinically significant findings and which does not require clinical action
• COHORT B: ANC (absolute neutrophil count) >= 1.5x10^9 cell/ml (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Platelets >= 150,000 /mm^3 (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Hemoglobin >= 11.0 g/dL (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of total serum bilirubin (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of AST (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of ALT (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of CPK (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of alkaline phosphatase (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of serum creatinine (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Normal concentrations of PT-INR/PTT (may be performed up to 28 days prior to the first administration of study treatment)
• COHORT B: Females who are post-menopausal only, which includes those who have had a hysterectomy, bilateral salpingectomy, and/or bilateral oophorectomy; no menses for at least 12 months without an alternative medical cause; or a high follicle-stimulating hormone (FSH) level consistently in the postmenopausal range (30 mIU/mL or higher) in women not using hormonal contraception or hormonal replacement therapy
• COHORT B: Male subjects with reproductive potential must be willing to use a condom with female partners of reproductive potential and their female sexual partners should use an additional highly effective method birth control (e.g. oral contraception and barrier methods, spermicide, and/or intrauterine device [IUD]). This requirement should be followed from screening through 24 weeks after last dose of immunotherapy
• COHORT B: Able and willing to comply with all study procedures

Exclusion Criteria

• COHORT A: Previous treatment with INO-5401 or IL-12 containing therapy, or any other DNA immunotherapy
• COHORT A: Prior history of invasive cancer other than those listed above. History of localized superficial non-melanoma skin cancers, melanoma in situ, cervical intraepithelial neoplasia, or breast ductal carcinoma in situ is allowed
• COHORT A: Pregnant or breast-feeding subjects
• COHORT A: Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation; subject’s continued participation in an observational study is allowed
• COHORT A: Cardiac pre-excitation syndromes, e.g. Wolff-Parkinson-White syndrome
• COHORT A: Prior major surgery within 4 weeks of first study treatment
• COHORT A: Presence of acute or chronic bleeding or clotting disorder that would contraindicate intramuscular (IM) injections, or use of blood thinners (e.g. anticoagulants or antiplatelet drugs) within 2 weeks of first study treatment
• COHORT A: Any concurrent condition requiring the continued or anticipated use of systemic steroids (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids) or immunosuppressive therapy (excludes low dose methotrexate). All systemic corticosteroids must be discontinued at least 4 weeks prior to first study treatment
• COHORT A: History of clinically significant autoimmune disease or other immunosuppressive disease
• COHORT A: Human immunodeficiency virus (HIV) infection
• COHORT A: Known history of hepatitis B and/or hepatitis C with active viral replication (i.e. hepatitis C virus [HCV] antibody reactive and HCV ribonucleic acid [RNA] detected)
• COHORT A: Receipt of any blood product within 2 weeks before signing the informed consent form (ICF)
• COHORT A: Administration of any vaccine, except the influenza vaccine, within 4 weeks of the first study treatment. Administration of influenza vaccine within two weeks of first study treatment
• COHORT A: Presence of metal implants or implantable medical device within 5 cm of the planned site of injection/electroporation (EP) including a cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the intended deltoid injection site, unless deemed acceptable by a cardiologist
• COHORT A: Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
• COHORT A: Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint
• COHORT A: Any other conditions judged by the investigator that would limit the evaluation of a subject
• COHORT B: Previous treatment with INO-5401 or IL-12 containing therapy, or any other DNA immunotherapy
• COHORT B: Prior history of invasive cancer. History of localized superficial non-melanoma skin cancers, melanoma in situ, cervical intraepithelial neoplasia, or breast ductal carcinoma in situ is allowed
• COHORT B: Pregnant or breast-feeding subjects
• COHORT B: Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation; subject’s continued participation in an observational study is allowed
• COHORT B: Cardiac pre-excitation syndromes, e.g. Wolff-Parkinson-White syndrome
• COHORT B: Prior major surgery within 4 weeks of first study treatment
• COHORT B: Presence of acute or chronic bleeding or clotting disorder that would contraindicate IM injections, or use of blood thinners (e.g. anticoagulants or antiplatelet drugs) within 2 weeks of first study treatment
• COHORT B: Any concurrent condition requiring the continued or anticipated use of systemic steroids (excluding non-systemic inhaled, topical skin and/or eye drop-containing corticosteroids) or immunosuppressive therapy (excludes low dose methotrexate). All systemic corticosteroids must be discontinued at least 4 weeks prior to first study treatment
• COHORT B: History of clinically significant autoimmune disease or other immunosuppressive disease
• COHORT B: HIV infection
• COHORT B: Known history of hepatitis B and/or hepatitis C with active viral replication (i.e. HCV antibody reactive and HCV RNA detected)
• COHORT B: Receipt of any blood product within 2 weeks before signing the ICF
• COHORT B: Administration of any vaccine, except the influenza vaccine, within 4 weeks of the first study treatment. Administration of influenza vaccine within two weeks of first study treatment
• COHORT B: Presence of metal implants or implantable medical device within 5 cm of the planned site of injection/EP including a cardioverter-defibrillator (ICD) or pacemaker (to prevent a life-threatening arrhythmia) that is located ipsilateral to the intended deltoid injection site, unless deemed acceptable by a cardiologist
• COHORT B: Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements
• COHORT B: Any illness or condition that in the opinion of the investigator may affect the safety of the subject or the evaluation of any study endpoint
• COHORT B: Any other conditions judged by the investigator that would limit the evaluation of a subject