A Randomized, Multicenter, Phase 3 Study of Zanidatamab in Combination with Chemotherapy with or without Tislelizumab in Subjects with HER2-positive Unresectable Locally Advanced or Metastatic Gastroesophageal Adenocarcinoma (GEA)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 251
- 试验地点
- 79
- 主要终点
- ●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)
研究概览
简要总结
To compare the efficacy of zanidatamab in combination with chemotherapy or in combination with chemotherapy and tislelizumab to the efficacy of trastuzumab in combination with chemotherapy in subjects with unresectable locally advanced, recurrent or metastatic HER2 positive GEA
研究设计
- 分配方式
- Randomized
- 主要目的
- Zanidatamab in Combination with Chemotherapy with or without Tislelizumab in HER2+ GEA Subjects
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •1.Histologically confirmed unresectable locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (adenocarcinomas of the stomach or esophagus, including the gastroesophageal junction), defined as 3+ HER2 expression by IHC or 2+ HER2 expression by IHC with ISHpositivity per central assessment. Subjects with esophageal adenocarcinoma must not be eligible for combined chemoradiotherapy at the time of enrollment. 2.Assessable (measurable or non-measurable) disease as defined by RECIST 1.
- •3.Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, assessed within 3 days prior to randomization 4.Adequate organ function 5.Left ventricular ejection fraction (LVEF) ≥ 50% as determined by either echocardiogram or multiple gated acquisition scan (MUGA)
排除标准
- •1.Prior treatment with a HER2-targeted agent, with the exception of subjects who received HER2-targeted treatment for breast cancer > 5 years prior to initial diagnosis of GEA. 2.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2 or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways.
- •Prior treatment with systemic antineoplastic therapy or intraperitoneal chemotherapy for unrespectable locally advanced, recurrent or metastatic GEA. 4.Untreated central nervous system (CNS) metastases, symptomatic CNS metastases, or radiation treatment for CNS metastases within 4 weeks prior to randomization. Stable, treated brain metastases are allowed (defined as subjects who are completely off steroids and anticonvulsantsand are neurologically stable with no evidence of radiographic progression for at least 4 weeks prior to randomization). 5.Known history of or ongoing leptomeningeal disease (LMD). 6.Known additional malignancy that is not considered cured or that has required treatment within the past 3 years. 7.Known active hepatitis 8.Any history of human immunodeficiency virus (HIV) infection 9.Known SARS-CoV-2 infection; subjects with prior infection that has resolved per local institutions' requirements and screening guidance are eligible 10.Clinically significant cardiac disease, such as ventricular arrhythmia requiring therapy, uncontrolled hypertension or any history of symptomatic congestive heart failure (CHF). 11.QTc Fridericia (QTcF) > 470 ms.
结局指标
主要结局
●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)
●Progression-free survival (PFS) by the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), assessed by blinded independent central review (BICR)
●Overall survival (OS) The primary PFS analysis will be performed once the target event count has been reached for each comparison. This is estimated to occur 7 months after the last subject is randomized. At this time, interim analyses of OS will be performed.
●Overall survival (OS) The primary PFS analysis will be performed once the target event count has been reached for each comparison. This is estimated to occur 7 months after the last subject is randomized. At this time, interim analyses of OS will be performed.
次要结局
- ●PFS by RECIST 1.1, per investigator assessment
- ●Confirmed objective response rate (ORR) by RECIST 1.1, assessed by BICR
- ●Duration of response (DOR) by RECIST 1.1, assessed by BICR
- ●Change from baseline in health economics and outcomes research / patient-reported outcomes (HEOR/PRO) parameters
- ●Serum concentration and PK parameters for zanidatamab
- ●Serum concentrations for tislelizumab
研究者
Medical Monitor
Scientific
Jazz Pharmaceuticals Ireland Limited