Phase Ib Trial of LEE011 With Everolimus (RAD001) and Exemestane in the Treatment of Hormone Receptor Positive HER2 Negative Advanced Breast Cancer

Inclusion Criteria

• •Adult women (≥ 18 years of age) with metastatic or locally advanced breast cancer
• •Histological or cytological confirmation of ER+ breast cancer in dose escalation and HR+ breast cancer in dose expansion
• •A representative tumor specimen must be available for molecular testing.
• •Postmenopausal women. Postmenopausal status is defined either by:
• •Age ≥ 18 with prior bilateral oophorectomy
• •Age ≥ 60 years
• •Age \<60 years with amenorrhea for at least 12 months and both follicle-stimulating hormone (FSH) and estradiol levels are in postmenopausal range (according to the local laboratory)
• •Recurrence while on, or within 12 months of end of adjuvant treatment with letrozole or anastrozole, or
• •Progression while on, or within one month of end of letrozole or anastrozole treatment for locally advanced or metastatic breast cancer.
• •Patients must have:
• •* Measurable disease\*: At least one lesion that can be accurately measured in at least one dimension ≥ 20 mm with conventional imaging techniques or ≥ 10 mm with spiral CT or MRI or
• •* Bone lesions: lytic or mixed (lytic + sclerotic) in the absence of measurable disease as defined above.
• •ECOG Performance Status 0-1.
• •Fasting serum cholesterol ≤ 300 mg/dl or 7.75 mmol/L and fasting triglycerides ≤ 2.5 × ULN. In case one or both of these thresholds are exceeded, the patient can only be included after initiation of statin therapy and when the above mentioned values have been achieved
• •Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory.
• •* QTcF interval at screening \< 450 msec (using Fridericia's correction).
• •* Resting heart rate 50-90 bpm
• •1. Group 1 - Patients must not have received prior treatment with any CDK4/6 inhibitors
• •2. Group 2 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapy
• •3. Group 3 - Patients must have disease progression while on or within one month after CDK4/6 inhibitor based therapy (except those patients who received prior LEE011 based therapy).
• •Other protocol-defined Inclusion/Exclusion may apply.