A Study of a Medicine Called Atirmociclib in Combination With Giredestrant in Adult Participants With ER-positive, HER2-negative Early-stage Breast Cancer

This Phase 3 study will evaluate whether atirmociclib plus giredestrant improves invasive breast cancer-free survival compared with giredestrant alone in adults with ER-positive, HER2-negative early breast cancer at medium or high risk of recurrence. This is a Phase 3, double blind, placebo controlled study of atirmociclib plus giredestrant vs. giredestrant monotherapy as adjuvant treatment in adult patients with ER+, HER2- early breast cancer. The study plans to enroll 3800 participants randomized 1:1 into one of two treatment arms (Arm A - investigational: atirmociclib plus giredestrant taken continuously in a 28-day cycle) or (Arm B - comparator: placebo plus giredestrant taken continuously in a 28-day cycle). Participants may be treated with atirmociclib/placebo up to 3 years and giredestrant up to 5 years followed by long term follow up for survival and evaluation of recurrence of disease.

KEY INCLUSION CRITERIA 1. Histologically confirmed unilateral primary adenocarcinoma of the breast * ER-positive by local assessment * documented HER2-negative 2. Node positive or node negative as defined by: * Pathological node positive (microscopic and/or macroscopic tumor involvement \>/=pN1) * pN0 and pT \>1cm with at least one of the following: 1. pT4N0 or 2. histologically Grade 3 disease or 3. high-risk classification based on genomic assay 3. Randomization within 16 months of definitive breast surgery 4. If indicated, completed adjuvant and/or neoadjuvant chemotherapy, adjuvant radiation therapy \>/= 21 days prior to randomization KEY EXCLUSION CRITERIA 1. Distant metastases of breast cancer beyond regional lymph nodes 2. Multicentric or multifocal breast cancer if any tumor foci meet pathologic criteria for ER(-) or HER2(+) 3. Clinically significant cardiovascular disease or cardiac repolarization abnormality for 6 months prior to randomization; resting heart rate \