Study to Assess the Safety and Efficacy of Ribociclib (LEE011) in Combination With Letrozole for the Treatment of Men and Pre/Postmenopausal Women With HR+ HER2- aBC

Inclusion Criteria:

- Male or female advanced (locoregionally recurrent or metastatic) breast cancer not
amenable to curative therapy.

- In the case of women, both pre/perimenopausal and postmenopausal patients are allowed
to be included in this study; menopausal status is relevant for the requirement of
goserelin to be used concomitantly with ribociclib and letrozole.

1. Postmenopausal status is defined either by:

I). Prior bilateral oophorectomy OR ii). Age ≥ 60 OR iii). Age < 60 and
amenorrhea for 12 or more months (in the absence of chemotherapy, tamoxifen,
toremifen, or ovarian suppression) and FSH and estradiol in the postmenopausal
range per local normal range. If patient is taking tamoxifen or toremifene and
age < 60, then FSH and plasma estradiol levels should be in post-menopausal range
per local normal range.

Note: For women with therapy-induced amenorrhea, serial measurements of FSH
and/or estradiol are needed to ensure menopausal status.

2. Premenopausal status is defined as either:

I). Patient had last menstrual period within the last 12 months, OR ii). If on
tamoxifen or toremifene within the past 14 days, plasma estradiol and FSH must be
in the premenopausal range per local normal range, OR iii). In case of therapy
induced amenorrhea, plasma estradiol and/or FSH must be in the premenopausal
range per local normal range.

3. Perimenopausal status is define as neither premenopausal nor postmenopausal Note:
Throughout this document, perimenopausal and premenopausal status is grouped
together and referred as "Premenopausal"

- 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 HER2-negative breast cancer defined as a negative in situ hybridization
test or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative in situ hybridization
(FISH, CISH, or SISH) test is required by local laboratory testing.

- Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2

- Patient has adequate bone marrow and organ function as defined by ALL of the following
laboratory values (as assessed by local laboratory):

- Absolute neutrophil count ≥ 1.5 × 10^9/L

- Platelets ≥ 100 × 10^9/L

- Hemoglobin ≥ 9.0 g/dL

- Potassium, sodium, calcium corrected for serum albumin and magnesium within
normal limits or corrected to within normal limits with supplements before first
dose of the study medication

- INR ≤1.5

- Serum creatinine <1.5 mg/dl or creatinine clearance≥50 mL/min

- In absence of liver metastases, alanine aminotransferase (ALT) and aspartate
aminotransferase (AST) should be below 2.5 × ULN. If the patient has liver
metastases, ALT and AST should be < 5 × ULN.

- Total serum bilirubin < ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
within normal range in patients with well-documented Gilbert's Syndrome

- Patient must have a 12-lead ECG with ALL of the following parameters at screening:

- QTcF interval at screening <450 msec (using Fridericia's correction)

- Resting heart rate ≥ 50 bpm

Exclusion Criteria:

- Patient who received any CDK4/6 inhibitor

- Patient who received any prior systemic hormonal therapy for advanced breast cancer;
no more than one prior regimen of chemotherapy for the treatment of metastatic disease
is permitted

Note:

- Patients who received (neo) adjuvant therapy for breast cancer are eligible. If the
prior neo (adjuvant) therapy included letrozole or anastrozole the disease free
interval must be greater than 12 months from the completion of treatment until study
entry.

- Patients who received ≤ 28 days of letrozole or anastrozole for advanced disease prior
to inclusion in this trial are eligible.

- Any prior (neo) adjuvant anti-cancer therapy or prior chemotherapy for metastatic
disease must be stopped at least 5 half-lives or 7 days, whichever is longer, before
study inclusion.

- Patient is concurrently using other anti-cancer therapy.