BYL719 + T-DM1 in HER2(+) Metastatic Breast Cancer Pts Who Progress on Prior Trastuzumab & Taxane Tx

Inclusion Criteria

• Patients must have histologically-confirmed HER2-positive breast cancer that is locally advanced or metastatic (stage 4); ideally this should be from biopsy of the metastatic disease; however if this is not available, histologic confirmation from the primary tumor is acceptable
• Patients must have had progression on a trastuzumab and taxane-based chemotherapy regimen during or after treatment for locally advanced or metastatic disease or within 6 months after treatment for early-stage HER2-positive disease documented by one of the following results using Food and Drug Administration (FDA)-approved testing methods:
• Fluorescence in situ hybridization (FISH)-positive (with an amplification ratio >= 2.0 indicating positive status) and/or
• Immunohistochemistry (IHC) 3 + by local laboratory assessment
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status = = 90 days
• Patients must have baseline laboratory tests within the following parameters at least 4 weeks (28 days) prior to registration:
• Hemoglobin > 8 g/dL (which may be reached by transfusion)
• Platelet count >= 100 x 10^9/L (no transfusion allowed within 2 weeks)
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L without growth factor support
• Serum bilirubin = = 50% LLN (lower limit of normal)
• Fasting plasma glucose (FPG) = 3 hypersensitivity reaction to trastuzumab, OR grade >= 1 with the most recent trastuzumab infusion before study entry, OR continued requirement for prolonged trastuzumab infusions to prevent hypersensitivity reactions are not eligible for participation
• Patients with a history of intolerance to trastuzumab and/or adverse events related to trastuzumab that resulted in trastuzumab being permanently discontinued are not eligible for participation
• Patients who have received prior treatment with T-DM1 are not eligible for participation
• Patients who have received prior anti-cancer therapy (e.g., biologic or other targeted therapy, chemotherapy, hormonal therapy) within 2 weeks prior to registration are not eligible for participation
• Patients with central nervous system (CNS) involvement may participate if the patient meets all of the following criteria:
• At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment
• Clinically stable with respect to the CNS tumor at the time of screening
• Not receiving steroid therapy
• Not receiving enzyme inducing anti-epileptic medications that were started for brain metastases
• Patients who have received radiotherapy = = 30% of the bone marrow was irradiated are not eligible for participation
• Patients who have undergone major surgery = = 2)
• Left ventricular ejection fraction (LVEF) 140/100 mm Hg at rest (average of 3 consecutive readings)
• History or current evidence of unstable, clinically significant cardiac arrhythmias or patients that require medications with a narrow therapeutic window, atrial fibrillation and/or conduction abnormality (e.g. congenital long QT syndrome, high-grade/complete atrioventricular [AV]-blockage)
• Acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass graft [CABG], coronary angioplasty, or stenting), 460 msec on screening ECG
• Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting plasma glucose (FPG) >= 140 mg/dL/7.8 mmol/L, or history of documented steroid-induced diabetes mellitus are not eligible for participation
• Patients exhibiting any other condition that would, in the Investigator's judgment, preclude patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures are not eligible for participation; this might include, but is not limited to, infection/inflammation, intestinal obstruction, and/or social/psychological complications
• Patients with impaired gastrointestinal (GI) function or GI disease that may s