Study of 2 Ribociclib Doses in Combination With Aromatase Inhibitors in Women With HR+, HER2- Advanced Breast Cancer

Prior treatment

• Patient who received any prior systemic anti-cancer therapy(including endocrine therapy, chemotherapy, prior CDK4/6 inhibitors) for aBC. Patients who received neo-/adjuvant therapy for breast cancer are eligible.
• Patient has had major surgery within 14 days prior to starting study drug or has not recovered from major toxicities.
• Patient has received extended-field radiotherapy ≤ 4 weeks or limited field radiotherapy ≤ 2 weeks prior to randomization, and has not recovered to grade 1 or better from related side effects of such therapy (with the exception of alopecia or other toxicities not considered a safety risk for the patient at investigator's discretion). Patients in whom ≥
• 25% of the bone marrow has been previously irradiated are also excluded.
• Patient has a concurrent malignancy or malignancy within 3 years of the randomization date, with the exception of adequately treated basal or squamous cell skin carcinoma, or curatively resected cervical carcinoma in situ.
• Patient is currently receiving or has received systemic corticosteroids ≤ 2 weeks prior to starting study drug, and has not fully recovered from side effects of such treatment.
  • Other protocol-defined Inclusion/Exclusion may apply.

Other illness

• Patient with symptomatic visceral disease or any disease burden that makes the patient ineligible for endocrine therapy per the investigator's judgment.
• Patient is concurrently using other anti-cancer therapy.
• Patient has clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality.

Other

• Patients with central nervous system (CNS) involvement unless they meet specific stability criteria.

• Patient has advanced (loco-regionally recurrent or metastatic) breast cancer not amenable to curative therapy.
• Patient has a histologically and/or cytologically confirmed diagnosis of ER-positive and/or PgR-positive breast cancer based on the most recently analyzed tissue sample, and all tested 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 and based on the most recently analyzed tissue sample.
• Patient must have measurable disease, i.e., at least one measurable lesion according to RECIST version 1.1. (a lesion in a previously irradiated site may only be counted as a target lesion if there is clear evidence of progression since the irradiation).
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed by the central laboratory:
  • QTcF interval at screening \< 450 ms (QT interval using Fridericia's correction)
  • Mean resting heart rate 50 to 90 bpm (determined from the ECG)
• Women of childbearing potential (CBP), defined as all women physiologically capable of becoming pregnant, must have confirmed negative serum pregnancy test (for β-hCG) within 14 days prior to randomization.
• Women of CBP must be willing to use highly effective methods of contraception.