Study of Efficacy and Safety of LEE011 in Men and Postmenopausal Women With Advanced Breast Cancer. (MONALEESA-3)

Inclusion Criteria:

1. Patient is an adult male/female ≥ 18 years old at the time of informed consent and has signed informed consent before any trial related activities and according to local guidelines. Female patients must be postmenopausal.
2. Patient has a histologically and/or cytologically confirmed diagnosis of estrogen-receptor positive and/or progesterone receptor positive breast cancer by local laboratory and has HER2-negative breast cancer.
3. Patient must have either measurable disease by RECIST 1.1 or at least one predominantly lytic bone lesion.

4. Patient has advanced (loco regionally recurrent not amenable to curative therapy, e.g. surgery and/or radiotherapy, or metastatic) breast cancer.

   Patients may be:

   • newly diagnosed advanced/metastatic breast cancer, treatment naïve
   • relapsed with documented evidence of relapse more than 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for advanced/metastatic disease
   • relapsed with documented evidence of relapse on or within 12 months from completion of (neo)adjuvant endocrine therapy with no treatment for advanced/metastatic disease
   • relapsed with documented evidence of relapse more than 12 months from completion of adjuvant endocrine therapy and then subsequently progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor) for advanced/metastatic disease
   • newly diagnosed advanced/metastatic breast cancer at diagnosis that progressed with documented evidence of progression after one line of endocrine therapy (with either an antiestrogen or an aromatase inhibitor)
5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Patient has adequate bone marrow and organ function

Exclusion Criteria:

1. Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's best judgment.
2. Patient has received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant or any CDK4/6 inhibitor.
3. Patient with inflammatory breast cancer at screening .
4. Patient with CNS involvement unless they are at least 4 weeks from prior therapy completion to starting the study treatment and have stable CNS tumor at the time of screening and not receiving steroids and/or enzyme inducing anti-epileptic medications for brain metastases
5. Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality

6. Patient is currently receiving any of the following substances and cannot be discontinued 7 days prior to start the treatment:

   • Known strong inducers or inhibitors of CYP3A4/5,
   • That have a known risk to prolong the QT interval or induce Torsades de Pointes.
   • Those have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5.
   • Herbal preparations/medications, dietary supplements.