A Randomized, Double-blind, Phase 3 Study of Tucatinib or Placebo in Combination With Trastuzumab and Pertuzumab as Maintenance Therapy for Metastatic HER2+ Breast Cancer (HER2CLIMB-05)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 654
- 试验地点
- 555
- 主要终点
- Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
研究概览
简要总结
This study is being done to see if tucatinib works better than placebo when given with other drugs to treat participants with HER2-positive breast cancer. A placebo is a pill that looks the same as tucatinib but has no medicine in it. This study will also test what side effects happen when participants take this combination of drugs. A side effect is anything a drug does to the body besides treating your disease.
Participants will have cancer that has spread in the body near where it started (locally advanced) and cannot be removed (unresectable) or has spread through the body (metastatic).
In this study, all participants will get either tucatinib or placebo. Participants will be assigned randomly to a group. This is a blinded study, so patients and their doctors will not know which group a participant is in.
All participants will also get trastuzumab and pertuzumab. These are 2 drugs used to treat this type of cancer.
详细描述
Control arm: Placebo given orally twice daily plus trastuzumab and pertuzumab every 21 days
Experimental arm: Tucatinib 300 mg given orally twice daily plus trastuzumab and pertuzumab every 21 days
Trastuzumab and pertuzumab will be administered as follows:
• Trastuzumab will be given intravenously (IV) at a dose of 6 mg/kg or subcutaneously (SC) at a fixed dose of 600 mg, once every 21 days.
AND
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Centrally confirmed HER2+ breast carcinoma according to the 2018 American Society of Clinical Oncologists (ASCO) College of American Pathologists (CAP) guidelines prior to randomization (defined as a 3+ score on immunohistochemistry (IHC) and/or 2+ IHC and concurrent positive by ISH).
- •Have unresectable locally advanced or metastatic disease.
- •If recurrent (after [neo]adjuvant therapy), must be at least 6 month treatment free from any trastuzumab and pertuzumab received in the early breast cancer setting for advanced HER2+ disease.
- •Have received 4-8 cycles of pre-study induction therapy including only trastuzumab, pertuzumab, and taxane as first-line of therapy for the treatment of advanced breast cancer prior to study enrollment. Participants are eligible provided they are without evidence of disease progression following completion of induction therapy.
- •Known hormone receptor status (per local guidelines; may be hormone receptor positive [HR+] or negative [HR-])
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •CNS Inclusion - Based on screening contrast-enhanced brain magnetic resonance imaging (MRI), participants may have any of the following:
- •No evidence of brain metastases
- •Untreated brain metastases which are asymptomatic not needing immediate local treatment and, if identified on prior brain imaging, without evidence of progression since starting first-line induction therapy with trastuzumab, pertuzumab, and taxane
- •Previously treated brain metastases which are asymptomatic
- •Brain metastases previously treated with local therapy must not have progressed since treatment
排除标准
- •Prior treatment with any tyrosine kinase inhibitor targeting HER2 and/or epidermal growth factor receptor (EGFR) including pyrotinib, lapatinib, tucatinib, neratinib, and afatinib (except neratinib if given in extended adjuvant setting and ≥ 12 months have elapsed since last neratinib dose prior to start of study drug)
- •Unable to undergo contrast-enhanced MRI of the brain
- •CNS Exclusion - Based on screening brain MRI and clinical assessment
- •Symptomatic brain metastasis after CNS-directed local therapy
- •Progression of brain metastases since starting first line trastuzumab, pertuzumab, and taxane
- •Ongoing use of systemic corticosteroids at a total daily dose of >2 mg of dexamethasone (or equivalent)
- •Any untreated brain lesion in an anatomic site which may pose risk to participant
- •Known or suspected leptomeningeal disease (LMD)
- •Poorly controlled (>1/week) seizures, or other persistent neurologic symptoms
研究组 & 干预措施
Tucatinib + trastuzumab + pertuzumab
Tucatinib + trastuzumab + pertuzumab
干预措施: Tucatinib (Drug)
Placebo + trastuzumab + pertuzumab
Placebo + trastuzumab + pertuzumab
干预措施: Placebo (Drug)
Tucatinib + trastuzumab + pertuzumab
Tucatinib + trastuzumab + pertuzumab
干预措施: Pertuzumab (Drug)
Placebo + trastuzumab + pertuzumab
Placebo + trastuzumab + pertuzumab
干预措施: Trastuzumab (Drug)
Placebo + trastuzumab + pertuzumab
Placebo + trastuzumab + pertuzumab
干预措施: Pertuzumab (Drug)
Tucatinib + trastuzumab + pertuzumab
Tucatinib + trastuzumab + pertuzumab
干预措施: Combination product: Trastuzumab + Pertuzumab (Drug)
Tucatinib + trastuzumab + pertuzumab
Tucatinib + trastuzumab + pertuzumab
干预措施: Trastuzumab (Drug)
Placebo + trastuzumab + pertuzumab
Placebo + trastuzumab + pertuzumab
干预措施: Combination product: Trastuzumab + Pertuzumab (Drug)
结局指标
主要结局
Progression-free survival (PFS) by investigator assessment per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
时间窗: Up to approximately 3 years
The time from the date of randomization to the investigator assessment of disease progression according to RECIST v1.1 or death from any cause
次要结局
- Trough concentration (Ctrough)(Through 30 days after last study treatment, approximately 18 months)
- Overall survival (OS)(Up to approximately 5 years)
- PFS by blinded independent central review (BICR) per RECIST v1.1(Up to approximately 3 years)
- Time to deterioration of health-related quality of life (HRQoL)(Up to approximately 3 years)
- Central nervous system (CNS) PFS(Up to approximately 3 years)
- Incidence of adverse events (AEs)(Through 30 days after last study treatment, approximately 18 months)
- Incidence of laboratory abnormalities(Through 30 days after last study treatment, approximately 18 months)
- Incidence of tucatinib dose alterations(Through 30 days after last study treatment, approximately 18 months)
- Incidence of trastuzumab dose alterations(Through 30 days after last study treatment, approximately 18 months)
- Incidence of pertuzumab dose alterations(Through 30 days after last study treatment, approximately 18 months)
- Maximum concentration (Cmax)(Through 30 days after last study treatment, approximately 18 months)