A Randomized, Open-label, Phase III Study of SIM0270 Combined With Everolimus Versus Treatment of Physician's Choice in Patients With CDK4/6 Inhibitors Previously Treated , ER+/HER2- Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 482
- 试验地点
- 59
- 主要终点
- Progression free survival(PFS) , as assessed by blinded independent review committee(BIRC) according to RECIST1.1
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •Advanced, symptomatic, visceral spread that is at risk of life-threatening complications in the short term
- •Active or symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
- •Active cardiac disease or history of cardiac dysfunction, as defined in the protocol
- •Pregnant or breastfeeding
研究组 & 干预措施
Control group
Investigator's choice of therapy of either:
Fulvestrant alone (a solution for injection), or Everolimus in combination with exemestane, both a tablet to be taken orally.
干预措施: Fulvestrant injection (Drug)
Experimental group
SIM0270 to be taken orally as a capsule in combination with Everolimus.
干预措施: SIM0270 (Drug)
Experimental group
SIM0270 to be taken orally as a capsule in combination with Everolimus.
干预措施: Everolimus (Afinitor®) (Drug)
Control group
Investigator's choice of therapy of either:
Fulvestrant alone (a solution for injection), or Everolimus in combination with exemestane, both a tablet to be taken orally.
干预措施: Everolimus (Afinitor®) (Drug)
Control group
Investigator's choice of therapy of either:
Fulvestrant alone (a solution for injection), or Everolimus in combination with exemestane, both a tablet to be taken orally.
干预措施: Exemestane tablets (Drug)
结局指标
主要结局
Progression free survival(PFS) , as assessed by blinded independent review committee(BIRC) according to RECIST1.1
时间窗: 2 year
PFS was defined as the time from the date of randomization to the first documented disease progression or death from any cause, whichever occurrs first.
次要结局
- ORR by BIRC(2 year)
- DOR by BIRC(2 year)
- Progression free survival(PFS) , as assessed by investigator according to RECIST1.1(2 year)
- Overall Survival (OS)(3 year)
- The incidence and severity of adverse events (AEs) and serious adverse events (SAEs)(3 year)
- Blood concentrations(At five specified time points of the first 6 cycles (each cycle is 28 days))
- Objective Response Rate (ORR) by investigator(2 year)
- Objective Response Rate (DOR) by investigator(2 year)
- Clinical benefit rate(CBR) by investigator(2 year)
- CBR by BIRC(2 year)
- Time To Progression (TTP) by investigator(2 year)
- Time To Progression (TTP) by BIRC(2 year)
- Change from baseline in EQ-5D-5L scores(2 year)
- Change from baseline in FACT-B scores(2 year)