Efficacy and Safety of Trastuzumab Rezetecan Followed by CDK4/6 Inhibitors and Endocrine Therapy in HR+/HER2-Low/Ultra-Low Advanced Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
研究概览
简要总结
This multicenter, prospective phase II clinical trial evaluates the efficacy and safety of sequential Trastuzumab rezetecan followed by dalpiciclib plus endocrine therapy (fulvestrant or aromatase inhibitors) in 45 patients with HR+/HER2-low/ultra-low advanced breast cancer. Enrolled patients will receive Trastuzumab rezetecan monotherapy for 6-8 cycles until clinical benefit, then transition to CDK4/6 inhibitors with endocrine therapy until disease progression or unacceptable toxicity. The primary endpoint is progression-free survival (PFS), with secondary endpoints including objective response rate (ORR), overall survival (OS), and treatment-related adverse events (TRAEs). The study will be conducted at Sun Yat-sen Memorial Hospital and collaborating centers.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Participants must meet all of the following criteria:
- •1. Female patients aged ≥18 years.
- •Pathologically confirmed HER2-low/ultra-low, HR-positive unresectable or metastatic breast cancer:
- •HER2-low: IHC 1+ or IHC 2+/ISH-negative；HER2-ultra-low: IHC 0 with membranous staining (>0 but <1+). HR+: ≥10% tumor cells with ER/PR nuclear staining (verified by central pathology review).
- •Disease stage: Recurrent/metastatic disease; locally recurrent cases must be deemed unresectable by investigators.
- •3. Prior therapy:
- •Disease progression after endocrine therapy (ET) + CDK4/6 inhibitor in the advanced/metastatic setting.
- •Progression within 12 months of adjuvant ET + CDK4/6 inhibitor allowed.
- •≤1 line of prior ET and ≤1 line of chemotherapy for advanced disease.
- •Measurable disease per RECIST 1.1 (including lytic/mixed bone-only metastases).
- •5. ECOG PS 0-
- •Adequate organ function (no transfusions/G-CSF within 2 weeks prior):
- •Hematologic: ANC >1.5×10⁹/L; platelets >90×10⁹/L; Hb >90 g/L.
- •Hepatic: Total bilirubin ≤ULN (≤2×ULN if Gilbert's syndrome). ALT/AST ≤1.5×ULN (≤5×ULN with liver metastases). Alkaline phosphatase ≤2.5×ULN.
- •Renal: BUN/Cr ≤1.5×ULN.
- •Cardiac: LVEF ≥50%;
- •QTcF <470 ms.
- •Voluntary participation with signed informed consent.
排除标准
- •Participants will be excluded if they meet any of the following conditions:
- •Prior anti-HER2 therapy at any stage (including HER2-ADCs such as T-DM1 or T-DXd).
- •Significant cardiac disease, including:
- •1) Heart failure or systolic dysfunction (LVEF <50%). 2) High-risk/treated angina or arrhythmias (e.g., Type II Mobitz II/third-degree AV block, ventricular tachycardia).
- •3) Clinically significant valvular disease. 4) ECG-confirmed transmural myocardial infarction. 5) Uncontrolled hypertension (systolic >150 mmHg and/or diastolic >100 mmHg).
- •Interstitial lung disease (ILD)/pneumonitis:
- •History of non-infectious ILD requiring steroids.
- •Current ILD or suspected ILD that cannot be ruled out by imaging at screening.
- •Impaired drug absorption due to:
- •1) Dysphagia, chronic diarrhea, intestinal obstruction, or other factors affecting oral medication intake.
- •5. Uncontrolled third-space effusions (e.g., pleural/peritoneal effusions) not manageable by drainage.
- •6. Pregnancy, lactation, or unwillingness to use effective contraception during and for 7 months post-treatment.
- •7. Other exclusions:
- •Severe comorbidities interfering with treatment (e.g., active HBV, pulmonary infections requiring therapy).
- •Any condition deemed unsuitable by investigators.
研究组 & 干预措施
HR+/HER2-low/ultra-low advanced breast cancer
Enrolled patients will be HR+/HER2-low/ultra-low advanced breast cancer patients and receive SHR-A1811 monotherapy for 6-8 cycles until clinical benefit, then transition to dalpiciclib with endocrine therapy until disease progression or unacceptable toxicity.
干预措施: Trastuzumab rezetecan + CDK4/6 inhibitors + endocrine therapy (Drug)
结局指标
主要结局
Progression-free survival (PFS)
时间窗: 2-year PFS
Progression-free survival rate at 2 years, calculated from the date of randomization to the first documented disease progression (per RECIST 1.1) or death due to any cause, whichever occurred first
次要结局
- Objective Response Rate (ORR)(ORR (CR+PR rate per RECIST 1.1) with ≥30% tumor reduction at 2 years post-enrollment, assessed by investigators)
- Clinical Benefit Rate (CBR)(CBR (CR+PR+SD≥24 weeks rate per RECIST 1.1) at 2 years post-enrollment, assessed by investigators.)
- Disease Control Rate (DCR)(DCR (CR+PR+SD rate per RECIST 1.1) at 2 years post-enrollment (investigator-assessed))
- Overall Survival (OS)(OS (time from enrollment to death) at 2-year follow-up (primary endpoint))
- Treatment-Related Adverse Events (TRAEs)(TRAEs (all AEs from first dose to 30 days post-treatment) graded by CTCAE v5.0, with causality assessment)
- Quality of Life (QoL)(QoL (EORTC QLQ-C30) evaluated serially from baseline to treatment discontinuation over 2 years)
研究者
Jianli Zhao
Breast cancer center
Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University