TOPAZ: Single Arm, Open Label Phase 1b/2 Study of Tucatinib in COmbination With Pembrolizumab And TrastuZumab in Patients With HER2-Positive Breast Cancer Brain Metastases
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- 24-week CNS disease control rate (DCR)
研究概览
简要总结
This is a single arm, open label trial to assess the safety and efficacy of tucatinib in combination with pembrolizumab and trastuzumab for the treatment of HER2+ breast cancer brain metastases (BCBM). A total of 33 patients with untreated or previously treated and progressing HER2+ BCBM not requiring urgent central nervous system (CNS)-directed therapy will be enrolled. The study will determine the recommended dose of tucatinib in this combination and assess the efficacy of this combination in controlling CNS disease in patients with HER2+ BCBM.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years.
- •ECOG performance status of 0-
- •HER2+ (as defined by ASCO/CAP clinical practice guideline) metastatic breast cancer.
- •Untreated or previously treated and progressing CNS disease.
- •Measurable CNS metastases.
- •Must be able to undergo MRI of the brain.
- •Adequate organ function.
排除标准
- •Any indication for immediate CNS-directed therapy.
- •History of generalized or complex partial seizures.
- •Any other manifestation of neurologic progression that in the opinion of the treating physician is due to brain metastases.
- •Leptomeningeal disease.
- •Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor.
- •Prior therapy with tucatinib.
- •Active autoimmune disease that has required systemic treatment in excess of prednisone 10mg daily or equivalent in the past 2 years.
- •Complete inclusion/exclusion criteria are detailed in the protocol.
研究组 & 干预措施
Tucatinib + Pembrolizumab + Trastuzumab
Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.
干预措施: Tucatinib (Drug)
Tucatinib + Pembrolizumab + Trastuzumab
Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.
干预措施: Pembrolizumab (Drug)
Tucatinib + Pembrolizumab + Trastuzumab
Patients will receive a combination therapy of tucatinib with pembrolizumab and trastuzumab during the treatment period until progression, treatment intolerance, or patient withdrawal from study. Tucatinib and pembrolizumab are administered as experimental use while trastuzumab is administered per standard use. Patients are expected to be on treatment for at least 12 weeks.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
24-week CNS disease control rate (DCR)
时间窗: 24 weeks
Percentage of patients who experience objective tumor response \[ partial response (PR) or complete response (CR) \] or stable disease as assessed by investigator per RANO-BM reads on protocol-specified MRIs of the brain.
Recommended dose of tucatinib in combination with pembrolizumab and trastuzumab
时间窗: 24 weeks
次要结局
- Systemic ORR(From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.)
- CNS objective response rate (ORR)(From baseline until the date of first documented progression or study discontinuation. Assessed up to 2 years.)
- Progression-free survival (PFS)(From baseline to first documentation of true progression or symptomatic deterioration, or death due to any cause. Assessed up to 2 years.)
- Overall Survival (OS)(From baseline until death or 3 years, whichever occurs first.)
- Toxicity profile of tucatinib, pembrolizumab, and trastuzumab co-administration(From first dose of study treatment until 30 days after the last dose of study treatment.)
研究者
Reva Basho
Assistant Professor of Medicine
Cedars-Sinai Medical Center