This Phase III, randomized, open label, multicenter study will evaluate the efficacy and safety of SIM0270 combined with everolimus compared to physician's choice of treatment in subjects with ER+/HER2- locally advanced or metastatic breast cancer who have had previous treatment with CDK4/6 inhibitor.

Inclusion criteria:

1. Subjects with histologically or cytologically confirmed ER+/HER2- locally advanced or metastatic breast cancer

2. Subjects must have at least one RECIST 1.1 measurable disease and /or at least 1 lytic or mixed (lytic + sclerotic) bone lesion

3. For women who are post menopausal must meet criteria as defined in the protocol.For women who are premenopausal or perimenopausal and for men: treatment with approved LHRH agonist therapy for screening period and the duration of study treatment

4. Have disease that has demonstrated progression on or after prior treatment:

   1. subjects had received 1 to 2 endocrine therapies in the locally advanced or metastatic setting with disease recurrence/disease progression while being treated with adjuvant endocrine therapy for ≥ 24 months and/or endocrine therapy in the locally advanced or metastatic setting, and derived a clinical benefit from therapy
   2. subjects had received ≤ 1 chemotherapy in the locally advanced or metastatic setting.

5. Eastern Cooperative Oncology Group Performance Status 0-1

6. Adequate organ function

exclusion criteria:

1. Prior treatment with a oral selective estrogen receptor degrader (SERD) or other investigational-ER-directed therapy, or any PI3K-AKI-mTOR inhibitors
2. Treatment with any investigational therapy within 28 days prior to study treatment.Treatment with moderate/strong CYP3A inhibitors or P-gP inhibitor within 14 days prior to first dose or moderate/strong CYP3A inducer within 28 days prior to first dose
3. Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
4. Active or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
5. Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
6. Pregnant or breastfeeding