Adjuvant Ribociclib With Endocrine Therapy in Hormone Receptor+/HER2- High Risk Early Breast Cancer

While adjuvant endocrine therapy (ET) is effective in reducing risk of recurrence in patients
with hormone receptor (HR)-positive early breast cancer (EBC), recurrences are still common,
especially in patients with unfavorable clinical, pathological and/or molecular features.
Ribociclib, a CDK4/6 inhibitor, demonstrated clinical efficacy with tolerable toxicity when
added to ET in patients with HR-positive, HER2-negative advanced breast cancer. The purpose
of this study is to evaluate the preliminary safety and tolerability of ribociclib to
standard adjuvant ET in patients with HR+, HER2- high-risk EBC.

Key Inclusion Criteria:

- Histologically confirmed unilateral primary invasive adenocarcinoma of the breast

- Estrogen receptor-positive and/or progesterone receptor-positive, HER2-negative breast
cancer

- Patient is after surgical resection of the tumor where tumor was removed completely,
with the final surgical specimen microscopic margins free from tumor and with
available archival tumor tissue from the surgical specimen

- Patient who received adjuvant chemotherapy and have AJCC 8th edition Prognostic Stage
Group III tumor; or patient who received neoadjuvant chemotherapy and have 1 or more
ipsilateral axillary lymph nodes with residual tumor metastases greater than 2.0 mm in
lymph node(-s) and residual tumor greater than 10.0 mm in breast tissue

- Patient has completed multi-agent adjuvant or neoadjuvant chemotherapy of ≥ 4 cycles
or ≥ 12 weeks which included taxanes prior to screening

- Patient has completed adjuvant radiotherapy (if indicated) prior to screening

- Patient may already have initiated adjuvant endocrine therapy (ET) at the time of
randomization, but randomization must take place within 52 weeks of date of initial
histological diagnosis of breast cancer and within 12 weeks of initiating ET

- ECOG Performance Status 0 or 1

- Adequate bone marrow and organ function

- Sodium, potassium, phosphorus, magnesium and total calcium laboratory values within
normal limits

- QTcF interval < 450 msec and mean resting heart rate 50-90 bpm

Key Exclusion Criteria:

- Prior treatment with CDK4/6 inhibitor

- Prior treatment with tamoxifen, raloxifen or aromatase inhibitors for reduction in
risk (chemoprevention) of breast cancer and/or treatment for osteoporosis within last
2 years

- Prior treatment with anthracyclines at cumulative doses of 450 mg/m² or more for
doxorubicin or 900 mg/m² or more for epirubicin

- Distant metastases of breast cancer beyond regional lymph nodes

- Patient has not recovered from clinical and laboratory acute toxicities of
chemotherapy, radiotherapy and surgery

- Clinically significant, uncontrolled heart disease and/or cardiac repolarization
abnormality, or clinically significant cardiac arrhythmias

- Uncontrolled hypertension with systolic blood pressure >160 mmHg

- Patient is currently receiving any of the prohibited substances that cannot be
discontinued 7 days prior to Cycle 1 Day 1: concomitant medications, herbal
supplements, and/or fruits and their juices that are known as strong inhibitors or
inducers of CYP3A4/5; medications that have a narrow therapeutic window and are
predominantly metabolized through CYP3A4/5; systemic corticosteroids ≤ 2 weeks prior
to starting study drug, or who have not fully recovered from side effects of such
treatment; concomitant medications with a known risk to prolong the QT interval and/or
known to cause torsades de points that cannot be discontinued or replaced by safe
alternative medication.

- Pregnant or breast-feeding (lactating) women or women who plan to become pregnant or
breast-feed during the study

- Women of child-bearing potential unless they are using highly effective methods of
contraception during the study treatment and for 21 days after stopping the study
treatment.