A Pharmacodynamics Pre-surgical Study of LEE011 in Early Breast Cancer Patients (MONALEESA-1)

This randomized pre-surgical pharmacodynamics study will assess the biological activity of
LEE011 plus letrozole versus single agent letrozole in primary breast cancer.

Inclusion Criteria:

- Female patient is ≥ 18 years old at the time of informed consent, with newly
diagnosed resectable breast cancer, who received no prior therapy for breast cancer

- Patient is postmenopausal. Postmenopausal status is defined either by:

- Prior bilateral oophorectomy

- Age ≥60

- Age <60 and amenorrhea for 12 or more months and FSH (Follicle Stimulating
Hormone) and estradiol in the postmenopausal range.

- Patient has a histologically (and/or cytologically) confirmed diagnosis of
estrogen-receptor positive and/or progesterone receptor positive breast cancer by
local laboratory.

- Patient has a grade II or grade III invasive breast cancer

- Patient has Human Epidermal Growth Factor Receptor 2 (HER2) negative breast cancer
defined as a negative in situ hybridization test or an Immunohistochemistry (IHC)
status of 0, 1+ or 2+ (if IHC 2+, a negative in situ hybridization (respectively
FISH/CISH/SISH) test is required) by local laboratory testing

- Patient has at least one breast lesion with a diameter of ≥1.0 cm by the most
accurate imaging modality used.

- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

Exclusion Criteria:

- Patient has received any prior therapy for breast cancer.

- Patient has a concurrent malignancy or malignancy within 3 years of randomization,
with the exception of adequately treated, basal cell skin cancer or squamous cell
carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer.

- Patient has active cardiac disease or a history of cardiac dysfunction including any
of the following:

- History of angina pectoris, symptomatic pericarditis, or myocardial infarction
within 12 months prior to study entry

- History of documented congestive heart failure (New York Heart Association
functional classification III-IV)

- Documented cardiomyopathy

- Patient has a Left Ventricular Ejection Fraction (LVEF) < 50% as determined by
Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO)

- History of ventricular, supraventricular, nodal arrhythmias, or any other
cardiac arrhythmias, Long QT Syndrome or conduction abnormality in the previous
12 months.

- Family history of QTc prolongation or of unexplainable sudden death at <50 years
of age.

- On screening 12 lead ECG, any of the following cardiac parameters: bradycardia
(heart rate < 50 at rest), tachycardia (heart rate > 90 at rest), PR interval >
220 msec, QRS interval >109 msec, or QTcF >450 msec.

- Systolic blood pressure >160 mmHg or <90 mmHg.

- Patient is currently receiving any of the following medications (see

Appendix 1 for details):

- That are known strong inducers or inhibitors of CYP3A4.

- That have a narrow therapeutic window and are predominantly metabolized through
CYP3A4.

- That have a known risk to prolong the QT interval or induce Torsades de Pointes.

Other protocol-defined inclusion/exclusion criteria may apply