Talimogene Laherparepvec with Chemotherapy or Endocrine Therapy in Treating Patients with Metastatic, Unresectable, or Recurrent HER2- Negative Breast Cancer

Inclusion Criteria

• Metastatic or locoregionally recurrent HER2-negative breast cancer; resectable disease allowed
• Ability to understand and voluntarily sign informed consent prior to undergoing any study-related assessments or procedures, as well as adhere to the study visit schedule and other protocol requirements
• Histologic or cytologic confirmation of invasive breast cancer that is HER2-negative by standard clinical criteria
• Patients who will participate in the endocrine therapy cohort must have invasive breast cancer that is estrogen receptor (ER) + (>= 1% ER staining by immunohistochemistry [IHC])
• At least one accessible and injectable lesion in the locoregional area (i.e. breast, chest wall, skin nodule or mass, axillary or supraclavicular lymph node) of at least 1 centimeter (cm); (ultrasound imaging may be used as clinically indicated; injection must be able to be performed at the bedside)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• Concomitant use of bisphosphonates, receptor activator of nuclear factor kappa-Β ligand (RANKL) antibody, and ovarian suppression is allowed
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L for chemotherapy cohort, and >= 1.0 x 10^9/L for endocrine therapy cohort
• Hemoglobin (Hgb) >= 9 g/dL
• Platelets (plt) >= 100 x 10^9/L for chemotherapy cohort, and >= 75,000 for endocrine therapy cohort
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper limit normal (ULN). If liver metastases present =< 5 x ULN allowed
• Serum total bilirubin =< 1.5 x ULN or direct bilirubin =< 1.5 x ULN in patients with well documented Gilbert’s syndrome
• Serum creatinine =< 1.5 x ULN, or 24-hour (hr) clearance >= 60 ml/min
• International normalization ratio (INR) or prothrombin time (PT) or partial thromboplastin time (PTT)/activated partial thromboplastin time (aPTT) =< 1.5 x ULN
• Females of child-bearing potential (FCBP) should have a negative urine or serum pregnancy test within 72 hours prior to enrollment. If urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. FCBP must also be willing to adhere to acceptable forms of birth control (a physician-approved contraceptive method: tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) during the study treatment and through 3 months after the last dose of talimogene laherparepvec. FCBP are defined as sexually mature women who: * Have not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or, * Have not been naturally postmenopausal for at least 12 consecutive months (i.e. has had menses at any time during the preceding 12 consecutive months) * Must be willing to practice abstinence or use effective contraception for a minimum of 3 months following completion of study treatment (in addition to during study therapy)

Exclusion Criteria

• Any significant medical condition, laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Any condition that confounds the ability to interpret data from the study
• Patients must have recovered from side effects resulting from prior cancer-directed therapy to a level of grade 1 or less (unless deemed not clinically significant by study investigator)
• Symptomatic central nervous system metastases; subjects with brain metastases that have been previously treated and are stable for 4 weeks after whole-brain radiotherapy (WBXRT) or 2 weeks after stereotactic radiosurgery (SRS) are allowed; patients must be stable off steroids for brain metastases for at least 7 days; subjects with asymptomatic clinically insignificant brain metastases not requiring treatment are allowed; the exception does not include carcinomatosus meningitis which is excluded regardless of clinical stability
• Patients with leptomeningeal disease
• History of symptomatic autoimmune disease or active autoimmune disease that has required systemic treatment in the 2 weeks prior to enrollment; replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
• Evidence of immune suppression due to: a) known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS); b) known leukemia or lymphoma; c) those who require high dose steroids (> 10 mg/day of prednisone or equivalent within 7 days prior to enrollment) or other immunosuppressive therapies (> 2 weeks); d) active hepatitis B or C; e) congenital or acquired cellular and/or humoral immune deficiency; f) other signs or symptoms of immune system suppression or concurrent opportunistic infection
• Nab-paclitaxel arm: grade 2 or higher neuropathy
• Known history of: cardiac disease, heart failure or decreased left ventricular ejection fraction, significant clinical arrhythmias
• Patients must not have received an investigational agent within 4 weeks or =< 5 half-lives, whichever is shorter, prior to starting study treatment
• Last dose of prior chemotherapy must be at least 2 weeks, and 2 weeks for targeted therapies, before first dose of study treatment. There is no required washout for endocrine therapy
• Major surgery or radiation =< 2 weeks prior to starting study treatment or who have not recovered from side effects of surgery or radiation
• Active herpetic skin lesions or prior complications of HSV-1 infection (e.g. herpetic encephalitis or keratitis)
• Lesions with underlying infection or clinically meaningful bleeding
• Requires intermittent or chronic systemic (intravenous or oral) treatment with an antiherpetic drug (e.g. acyclovir), other than intermittent topical use; patients requiring anti-herpetic prophylaxis during chemotherapy are excluded
• Previous treatment with talimogene laherparepvec or any other oncolytic virus
• Prior therapy with tumor vaccine
• Received live vaccine within 28 days prior to enrollment
• Known allergic reaction to talimogene laherparepvec, nab-paclitaxel, gemcitabine, carboplatin, aromatase inhibitors, tamoxifen, fulvestrant, or any of their components. An exception is made if the patient will not be receiving the offending agent/component (i.e. a patient who is allergic to nab-paclitaxel but will be receiving endocrine therapy is eligible)
• Patients on therapeutic anticoagulation that cannot be held around injections
• Women who are pregnant or breast-feeding
• FCBP who are unwilling to use acceptable method(s) of effective contraception during study treatment and through 3 months after the last dose of talimogene laherparepvec
• Sexually active subjects and their partners unwilling to use a male or female latex condom to avoid potential viral transmission during sexual contact while on treatment and within 30 days after treatment with talimogene laherparepvec
• Subjects who are unwilling to minimize exposure with his/her blood or other body fluids to individuals who are at higher risks for HSV 1 induced complications (immunosuppressed individuals, HIV positive individuals, pregnant women, or children under the age of 1 year) during talimogene laherparepvec treatment and through 30 days after the last dose of talimogene laherparepvec