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

A Phase III, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate Efficacy and Safety of Ribociclib With Endocrine Therapy as an Adjuvant Treatment in Patients With Hormone Receptor-positive, HER2-negative, Intermediate Risk Early Breast Cancer

This is an international, multi-center, randomized, double-blinded, placebo-controlled clinical study evaluating the efficacy and safety of ribociclib with endocrine therapy as an adjuvant treatment in patients with hormone receptor-positive, HER2-negative, intermediate risk 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 effect of addition of ribociclib to standard adjuvant ET on invasive disease-free survival in patients with HR+, HER2- intermediate-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 surgical specimen microscopic margins free from tumor and with available archival tumor tissue from the surgical specimen
• Patient who have AJCC 8th edition Prognostic Stage Group II
• Patient has completed adjuvant radiotherapy (if indicated) according to the institutional guidelines 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 neoadjuvant therapy (endocrine therapy or chemotherapy) or 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
• Patient with inflammatory breast cancer
• 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.