A Phase Ib/II Study of BEZ235 and Trastuzumab in Patients With HER2-positive Breast Cancer Who Failed Prior to Trastuzumab

Inclusion Criteria: * Patient is a female ≥ 18 years of age * Patient has a histologically and/or cytologically confirmed diagnosis of HER2-positive invasive breast cancer with inoperable locally advanced or metastatic disease * Patients with controlled or asymptomatic CNS metastases are eligible * Patient has adequate bone marrow and organ functions, and has recovery from all clinically significant toxicities related to prior anti-neoplastic therapies * Absolute neutrophil count (ANC) ≥ 1.5 x 109/L * Platelets ≥ 100 x 109/L * Hemoglobin (Hgb) ≥ 9.0 g/dL * INR ≤ 2 * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 x ULN (or ≤ 5.0 x ULN if liver metastases are present) * Total serum bilirubin ≤ 1.5 x ULN (in patients with known Gilbert Syndrome, a total bilirubin ≤ 3.0 x ULN, with direct bilirubin ≤ 1.5 x ULN) * Serum creatinine ≤ 1.5 x ULN * Fasting plasma glucose (FPG) ≤ 140mg/dL \[7.8 mmol/L\] * HbA1c ≤ 8% * Patient has received prior trastuzumab (alone or in combination) but NO more than 3 prior cytotoxic chemotherapy lines * Prior endocrine and radiotherapy allowed * Patient has ECOG performance status of 0-2 (Phase Ib) or 0-1 (Phase II) Additional inclusion criteria for phase II: * Available tumor tissue (archival or fresh) for biomarker analysis; known PI3K activation status * At least one measurable lesion as per RECIST 1.1 * Patient has received prior treatment with a taxane * Patient has "trastuzumab-resistance disease" defined as: * Recurre…