Safety, Tolerability, and Efficacy Study in Subjects With Advanced or Metastatic Breast Cancer

Inclusion Criteria

Histopathologically or cytologically confirmed, advanced or metastatic breast cancer (stage IIIb, IIIc or IV disease) including inflammatory breast cancer or inoperable locally advanced disease.
Documented ErbB2 overexpression
Estrogen receptor positive (ER+) and/or progesterone positive (PgR+) tumors
Measurable or non-measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Criteria
A life expectancy of > 3 months for Phase 1 and > 6 months for Phase 2
Eastern Cooperative Oncology Group (ECOG) performance status score of ≤ 2 at study entry in Phase 1 and ≤ 1 in Phase 2;
Normal cardiac ejection fraction
Adequate hematologic, hepatic and renal function
Post-menopausal female (defined as the absence of a menstrual cycle for at least 12 consecutive months) or male subjects ≥ 18 years of age.
Sign an IRB or EC approved informed consent

Exclusion Criteria

Type 1 diabetes or uncontrolled Type 2 diabetes
Subjects showing clinical evidence or with a history of cataract(s), proliferate retinopathy or significant macular edema
Subjects with abnormal free T4 values and a history or evidence of thyroid disease
Subjects who are unable or unwilling to take metformin
Uncontrolled intercurrent illness
Known or suspected human immunodeficiency virus (HIV) infection or hepatitis B or C
Subjects with inflammatory diseases of the gastrointestinal tract
History of other malignancy. Subjects who have been disease free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible;
Subjects with extensive symptomatic visceral disease including hepatic involvement and pulmonary lymphangitic spread of tumor
A history of prior treatment with other agents specifically targeting IGFRs
Subjects who require pharmacological doses of glucocorticoids beyond replacement doses. The use of topical, intra-ocular or inhalation glucocorticoids is permitted