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

A Randomized Pre-surgical Pharmacodynamics Study to Assess the Biological Activity of LEE011 Plus Letrozole Versus Single Agent Letrozole in Primary Breast Cancer

This is a multi-center, open-label Phase II randomized pre-surgical pharmacodynamics study.

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