The main purpose of this study is to evaluate the efficacy and safety of GB491 combined with Letrozole versus placebo combined with Letrozole in the treatment of HR+/HER2- locally advanced or metastatic breast cancer without prior systemic antitumor therapy

Inclusion Criteria:

• 1. Age: 18-75 years old;
• Have a pathologically-confirmed diagnosis of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer;
• No previous systematic antitumor therapy for locally advanced or metastatic breast cancer;
• Eastern Cooperative Oncology Group [ECOG] 0-1;
• Have adequate organ and marrow function;
• Agree to sign the informed consent;

Exclusion Criteria:

• Systematic treatment with any other CDK4/6 inhibitor；
• Subjects with known allergy to GB491 or any component of Letrozole；
• Confirmed diagnosis of HER2 positive disease;
• Known uncontrolled, or symptomatic central nervous system metastases;
• Had major surgery (or is expected to require major surgery during the study period), chemotherapy, radiation, any investigational drug, or other antitumor therapy within 4 weeks prior to randomization;
• Have previously received chemotherapy for locoregionally recurrent or metastatic breast cancer;
• Clinically significant cardiovascular and cerebrovascular diseases, including but not limited to severe acute myocardial infarction within 6 months before enrollment, unstable or severe angina, Congestive heart failure, or ventricular arrhythmia which need medical intervention；
• Known history of HIV infection or HIV seropositivity (including HIV antibody positive at the time of screening)