Efficacy and Safety of SHR-A1811 Versus Pyrotinib Plus Capecitabine in Patients With Trastuzumab Primary-Resistant HER2-Positive Advanced Breast Cancer：A Prospective, Multicenter, Open-Label, Randomized, Controlled Study
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 100
- 主要终点
- PFS during treatment phase 1
研究概览
简要总结
This is a prospective, multicenter, open-label, randomized, controlled Study. The purpose of this study is to evaluate the efficacy and safety of SHR-A1811 versus pyrotinib plus capecitabine in the treatment of trastuzumab primary-resistant HER2-positive advanced breast cancer.
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
- •Age ≥18 years.
- •Histologically or cytologically confirmed HER2-positive advanced breast cancer (IHC 3+, or IHC 2+ with ISH amplification).
- •ECOG performance status 0-
- •Estimated life expectancy >12 weeks.
- •At least one measurable lesion per RECIST v1.1 criteria;
- •Patients with trastuzumab primary resistance is defined as follows:
- •Progression during or within 12 months after treatment in neoadjuvant or adjuvant setting (at least 9 weeks of trastuzumab treatment);
- •For patients with de novo stage IV disease, progression during or within 3 months after treatment for locally advanced or metastatic disease in the first-line setting (at least 6 weeks of trastuzumab treatment).
- •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%.
- •Women of childbearing potential must have a negative pregnancy test at screening, and subjects of reproductive potential must agree to use effective contraception from study start until 6 months after the last dose of study treatment..
- •Voluntary participation with written informed consent obtained prior to any study-related procedures.
排除标准
- •Prior or current exposure to antibody-drug conjugates (ADCs) containing a topoisomerase I inhibitor, including but not limited to fam-trastuzumab deruxtecan (DS-8201a).
- •Active brain metastases or leptomeningeal metastases (patients with asymptomatic/inactive brain metastases are allowed to be enrolled);
- •Other malignancy diagnosed within 5 years prior to enrollment, excluding cured non-melanoma skin cancer, cervical carcinoma in situ, ductal carcinoma in situ, or stage I grade 1 endometrial cancer;
- •Radiotherapy, any anti-HER2 targeted therapy, or chemotherapy within 4 weeks prior to enrollment; endocrine therapy within 2 weeks prior to enrollment;
- •Positive for human immunodeficiency virus (HIV);
- •Known hypersensitivity to any study drug or its excipients, or to humanized monoclonal antibody products (e.g., trastuzumab, pertuzumab, etc.);
- •Clinically significant cardiovascular disease, such as severe/unstable angina, symptomatic congestive heart failure (NYHA Class ≥II), clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention, myocardial infarction within 6 months prior to first 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 1
Treatment Phase 1: SHR-A1811 monotherapy until progression or intolerable adverse events.
Treatment Phase 2: Switch to pyrotinib plus capecitabine upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.
干预措施: SHR-A1811 (Drug)
Arm 1
Treatment Phase 1: SHR-A1811 monotherapy until progression or intolerable adverse events.
Treatment Phase 2: Switch to pyrotinib plus capecitabine upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.
干预措施: Pyrotinib (Drug)
Arm 1
Treatment Phase 1: SHR-A1811 monotherapy until progression or intolerable adverse events.
Treatment Phase 2: Switch to pyrotinib plus capecitabine upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.
干预措施: Capecitabine (Drug)
Arm 2
Treatment Phase 1: Pyrotinib plus capecitabineuntil progression or intolerable adverse events.
Treatment Phase 2: Switch to T-DXd upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.
干预措施: Pyrotinib (Drug)
Arm 2
Treatment Phase 1: Pyrotinib plus capecitabineuntil progression or intolerable adverse events.
Treatment Phase 2: Switch to T-DXd upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.
干预措施: Capecitabine (Drug)
Arm 2
Treatment Phase 1: Pyrotinib plus capecitabineuntil progression or intolerable adverse events.
Treatment Phase 2: Switch to T-DXd upon progression from Phase 1, continued until subsequent progression or intolerable adverse events.
干预措施: T-DXd (Drug)
结局指标
主要结局
PFS during treatment phase 1
时间窗: Start of treatment until 2-year follow-up
progression free survival during treatment phase 1 : time from randomization to the first observation of tumor progression or death from any cause during treatment phase 1.
次要结局
- Total PFS across treatment phase 1 and treatment phase 2(Start of treatment until 3-year follow-up)
- PFS during treatment phase 2(Start of treatment until 3-year follow-up)
- ORR during treatment phase 1(Start of treatment until 2-year follow-up)
- DCR during treatment phase 1(Start of treatment until 2-year follow-up)
- OS(Start of treatment until 3-year follow-up)
- Incidence of adverse events(Start of treatment until 3-year follow-up)
- Severity of adverse events(Start of treatment until 3-year follow-up)
- Incidence of serious adverse events(Start of treatment until 3-year follow-up)
- Severity of serious adverse events(Start of treatment until 3-year follow-up)
研究者
Hanfang Jiang, MD
Professor
Peking University Cancer Hospital & Institute