NCT07177950尚未招募1 期
A Two-cohort Study of SHR-A1811 in the Treatment of HER2-positive Breast Cancer With Brain Metastases, With or Without Leptomeningeal Metastases.
Peking University Cancer Hospital & Institute0 个研究点目标入组 51 人开始时间: 2025年9月30日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 51
- 主要终点
- 1. Number of Dose-Limiting Toxicities (DLTs) in the Sequential Dose-Escalation Cohort
研究概览
简要总结
This is a multi-center, open-label, two-cohort study. The purpose of this study is to evaluate the safety, tolerability and efficacy of SHR-A1811 in the treatment of HER2-positive breast cancer with brain and leptomeningeal metastases, and the efficacy and safety of SHR-A1811 in the treatment of HER2-positive breast cancer with brain but without leptomeningeal metastases.
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 75 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Women aged 18-75 years (inclusive).
- •Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification).
- •Radiologically documented brain metastases, with or without baseline leptomeningeal disease:
- •Cohort A (leptomeningeal metastasis cohort): leptomeningeal involvement demonstrated by contrast-enhanced MRI or positive cerebrospinal fluid (CSF) cytology.
- •Cohort B (no leptomeningeal metastasis cohort): ≥1 measurable intracranial lesion; either CNS-naïve or progressive after prior local therapy.
- •Anticipated life expectancy >12 weeks.
- •ECOG performance status 0-
- •Adequate organ function as defined by the following laboratory criteria:
- •Hematologic: absolute neutrophil count (ANC) ≥1.5 × 10⁹/L, platelet count (PLT) ≥100 × 10⁹/L, hemoglobin (HGB) ≥90 g/L.
- •Hepatic: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 × upper limit of normal (ULN) (≤5 × ULN in patients with liver metastases); total serum bilirubin (TBIL) ≤1.5 × ULN; serum albumin ≥30 g/L.
- •Renal: serum creatinine (Cr) ≤1.5 × ULN or calculated creatinine clearance ≥50 mL/min using the Cockcroft-Gault formula.
- •Coagulation: prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5 × ULN.
- •Cardiac: left ventricular ejection fraction (LVEF) ≥50%.
- •Negative serum pregnancy test; women of childbearing potential must use a highly effective contraceptive method from study initiation until at least 6 months after the last dose of study medication.
- •Voluntary participation with written informed consent obtained prior to any study-related procedures.
排除标准
- •Cohort A participants must be excluded if any of the following apply:
- •Cerebrospinal fluid (CSF) circulation obstruction that cannot be adequately controlled by therapeutic measures.
- •MRI evidence of nodular leptomeningeal (LM) disease in the setting of negative CSF cytology.
- •Active central nervous system (CNS) infection.
- •Clinically significant coagulopathy.
- •Cohort B participants must be excluded if leptomeningeal metastasis is documented, defined as either: radiographic evidence of leptomeningeal involvement, or positive CSF cytology, or unequivocal clinical signs or symptoms attributable to leptomeningeal disease.
- •Presence of clinically significant third-space fluid accumulation (e.g., massive pleural or peritoneal effusion) that cannot be adequately controlled by drainage or other interventions.
- •Known hypersensitivity to any study drug or its excipients, or to any prior humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab).
- •Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a).
- •Clinically significant cardiovascular disease, including but not limited to: severe or unstable angina pectoris, symptomatic congestive heart failure (New York Heart Association class ≥ II), clinically relevant supraventricular or ventricular arrhythmias requiring therapy or intervention, myocardial infarction within 6 months prior to first study dose, or cerebrovascular accident (including transient ischemic attack).
- •Participants known or suspected to interstitial lung disease.
- •Concurrent participation in any other interventional drug clinical trial.
- •Refusal to comply with protocol-mandated follow-up.
- •Presence of any additional severe physical or psychiatric disorder, or any laboratory abnormality that, in the investigator's judgment, could increase the subject's risk, confound study results, or render the patient unsuitable for enrollment.
研究组 & 干预措施
Arm 2
Experimental
Systemic SHR-A1811 therapy combined with radiotherapy
干预措施: radiotherapy (Radiation)
Arm 2
Experimental
Systemic SHR-A1811 therapy combined with radiotherapy
干预措施: SHR-A1811 (Drug)
Arm 1
Experimental
Systemic SHR-A1811 therapy combined with intrathecal SHR-A1811 therapy
干预措施: SHR-A1811 (Drug)
结局指标
主要结局
1. Number of Dose-Limiting Toxicities (DLTs) in the Sequential Dose-Escalation Cohort
时间窗: Start of treatment until 3-week follow-up
For cohort A. DLT is defined as any of the following events judged by the investigator to be related or possibly related to SHR-A1811 occurring within Cycle 1 (21 days), graded according to NCI-CTCAE v5.0: 1. Grade ≥3 neurologic toxicity; 2. Any death unless unequivocally attributable to tumor progression or an unrelated exogenous cause.
CNS-PFS
时间窗: Start of treatment until 2-year follow-up
For cohort B: Central nervous system- progression free survival: time from the date when the subject first received SHR-A1811 to the first observation of tumor progression of central nervous system or death from any cause.
次要结局
- CNS-PFS(Start of treatment until 2-year follow-up)
- CNS-ORR(Start of treatment until 2-year follow-up)
- PFS(Start of treatment until 2-year follow-up)
- OS(Start of treatment until 2-year follow-up)
- Quality of life score(Start of treatment until 2-year follow-up)
- Incidence and severity of adverse events (AE) and serious adverse events (SAE)(Start of treatment until 2-year follow-up)
研究者
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