A Study of SIM0270 Combined With Everolimus vs. Treatment of Physician's Choice in Patients With ER+/HER2- Advanced Breast Cancer (SIMRISE)

Prior treatment

• Prior treatment with a oral selective estrogen receptor degrader (SERD) or other investigational-ER-directed therapy, or any PI3K-AKI-mTOR inhibitors
• 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

Other illness

• Active or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
• Active cardiac disease or history of cardiac dysfunction, as defined in the protocol

Other

• Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
• Pregnant or breastfeeding

• Subjects with histologically or cytologically confirmed ER+/HER2- locally advanced or metastatic breast cancer
• Subjects must have at least one RECIST 1.1 measurable disease and /or at least 1 lytic or mixed (lytic + sclerotic) bone lesion
• 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
• Have disease that has demonstrated progression on or after prior treatment:
  • 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
  • subjects had received ≤ 1 chemotherapy in the locally advanced or metastatic setting.
• Eastern Cooperative Oncology Group Performance Status 0-1
• Adequate organ function