Real-world Cohort Study on Sequential Therapy With ADC Drugs Following Progression of Endocrine Therapy Guided by Molecular Biomarkers in HR-positive/HER2-negative Advanced Breast Cancer
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Progression-Free Survival (PFS1)
研究概览
简要总结
The combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy is the standard first-line treatment for advanced HR+ (hormone receptor-positive)/HER2- (human epidermal growth factor receptor 2-negative) breast cancer. However, the optimal treatment strategy after CDK4/6i progression remains unclear. In recent years, antibody-drug conjugates (ADCs) such as sacituzumab govitecan (SG) and trastuzumab deruxtecan (T-DXd) have demonstrated significant activity in HR+/HER2- breast cancer, providing new options post-CDK4/6i progression. Yet, the optimal sequencing of different ADCs (e.g., SG followed by T-DXd vs. T-DXd followed by SG) after CDK4/6i failure remains uncertain. Determining how to further optimize treatment selection to prolong survival and improve quality of life has become a key research focus in clinical practice. This study aims to explore the efficacy, safety, and potential resistance mechanisms of biomarker-guided sequential ADC therapy (e.g., SG→T-DXd vs. T-DXd→SG) following CDK4/6i progression. The findings may guide clinical decision-making and provide evidence for precision medicine.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 85 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Adult patients ≥18 years old;
- •Histologically or cytologically confirmed HR+/HER2- (HER2 IHC 0/IHC 1+ or IHC 2+ with FISH-negative) locally advanced unresectable or metastatic breast cancer, as defined by ASCO/CAP guidelines;
- •Prior treatment with CDK4/6i combined with endocrine therapy, with radiologically confirmed disease progression;
- •Presence of evaluable lesions;
- •Received ≤2 lines of chemotherapy for advanced disease;
- •Adequate organ function and performance status (ECOG score ≤2);
- •Signed informed consent.
排除标准
- •Previous treatment with topoisomerase 1 (TOP-1) inhibitor-based therapy;
- •Severe cardiac, hepatic, or renal dysfunction or other serious comorbidities;
- •History of moderate to severe interstitial lung disease (ILD) with concurrent pulmonary insufficiency;
- •Symptomatic brain metastases;
- •History of allergy to key components of the investigational ADC drugs (e.g., payload, antibody, or linker);
- •Patients with active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or a history of intestinal obstruction or gastrointestinal (GI) perforation;
- •Uncontrolled cardiovascular diseases (e.g., NYHA Class III/IV heart failure, myocardial infarction within 6 months);
- •Active infections (e.g., HIV, active HBV/HCV infection);
- •Pregnant or lactating women.
研究组 & 干预措施
Cohort 1 (HER2 IHC 2+)
Patients will be assigned to Cohort 1 (HER2 Immunohistochemistry，IHC，2+) based on different HER2 immunohistochemical expression levels, where they will first receive T-DXd treatment, followed by SG treatment upon disease progression.
干预措施: First-line T-DXd followed by SG upon disease progression (Drug)
Cohort 2 (HER2 IHC ≤1+)
Patients will be assigned to Cohort 2 (HER2 IHC ≤1+) based on different HER2 immunohistochemical expression levels, where they will first receive SG treatment, followed by T-DXd treatment upon disease progression.
干预措施: First-line SG followed by T-DXd upon progression (Drug)
结局指标
主要结局
Progression-Free Survival (PFS1)
时间窗: From the date of signing the informed consent form until the date of first documented disease progression after initial ADC therapy or date of death from any cause (whichever occurs first), assessed up to 24 months.
PFS1 is defined as the time from signing the informed consent form to the first documented disease progression after initial ADC therapy or death from any cause, whichever occurs first.
次要结局
- Progression-Free Survival 2 (PFS2)(From the date of initiation of the second ADC therapy (ADC2) until the date of further documented disease progression or date of death from any cause (whichever occurs first), assessed up to 24 months.)
- Composite Progression-Free Survival (PFS-Total)(From the date of signing the informed consent form until the date of the first documented disease progression (during ADC1 or ADC2 therapy) or date of death from any cause (whichever occurs first), assessed up to 36 months.)
- Overall Survival (OS)(From the date of randomization until the date of death from any cause, assessed up to 60 months.)
- Objective Response Rate（ORR）(At least 4 weeks after first documented response)
研究者
Yan Xue
Director of the First Department of Oncology, Xi'an International Medical Center Hospital
Xi'an International Medical Center Hospital