This study will evaluate the efficacy and safety of the combination of inavolisib plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i) and letrozole versus placebo plus a CDK4/6i and letrozole in the first-line setting in participants with endocrine-sensitive PIK3CA-mutated hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer (ABC).
Women or men with histologically or cytologically confirmed carcinoma of the breast
Documented ER-positive and/or progesterone receptor-positive tumor according to American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
Documented HER2-negative tumor according to ASCO/CAP guidelines
De-novo HR+ , HER2- ABC, or, alternatively, relapsed HR+ , HER2- ABC after at least 2 years of standard neoadjuvant/adjuvant endocrine therapy without disease progression during that treatment and disease-free interval of at least 1 year since the completion of that treatment
Pregnant or breastfeeding, or intention of becoming pregnant during the study or within the time frame in which contraception is required
Metaplastic breast cancer
Any prior systemic therapy for locally advanced unresectable or metastatic breast cancer
Type 2 diabetes requiring ongoing systemic treatment at the time of study entry; or any history of Type 1 diabetes