NCT04539938已完成2 期
A Single Arm, Open Label Phase 2 Study of Tucatinib in Combination With Trastuzumab Deruxtecan in Subjects With Previously Treated Unresectable Locally-Advanced or Metastatic HER2+ Breast Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 70
- 试验地点
- 232
- 主要终点
- Confirmed Objective Response Rate (cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 According to Investigator (INV) Assessment
研究概览
简要总结
This trial studies how well the drug tucatinib works when given with trastuzumab deruxtecan (T-DXd). It will also look at what side effects happen when these drugs are given together. A side effect is anything a drug does besides treating cancer.
Participants in this trial have HER2-positive (HER2+) breast cancer that has either spread to other parts of the body (metastatic) or cannot be removed completely with surgery (unresectable). All participants will get both tucatinib and T-DXd.
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
- •Have confirmed HER2+ breast cancer, as defined by the current American Society of Clinical Oncology - College of American Pathologists (ASCO/CAP) guidelines, previously determined at a Clinical Laboratory Improvements Amendments (CLIA)-certified or International Organization for Standardization (ISO)-accredited laboratory.
- •History of prior treatment with a taxane and trastuzumab in the LA/M setting OR progressed within 6 months after neoadjuvant or adjuvant treatment, including a taxane and trastuzumab.
- •Have progression of unresectable LA/M breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy
- •Have measurable disease assessable by RECIST v1.1
- •Have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1
- •Have a life expectancy of at least 6 months, in the opinion of the investigator
- •CNS Inclusion - Based on medical history and screening contrast brain magnetic resonance imaging (MRI), participants with a history of brain metastases must have one of the following:
- •Untreated brain metastases not needing immediate local therapy. For participants with untreated central nervous system (CNS) lesions >2.0 cm on screening contrast brain MRI, discussion with and approval from the medical monitor is required prior to enrollment
- •Previously treated brain metastases
- •Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator
- •Participants treated with CNS local therapy for newly identified or previously treated progressing lesions found on contrast brain MRI performed during screening for this study may be eligible to enroll if all of the following criteria are met:
- •Time since whole brain radiation therapy (WBRT) is ≥14 days prior to first dose of study treatment, time since stereotactic radiosurgery (SRS) is ≥7 days prior to first dose of study treatment, or time since surgical resection is ≥28 days
- •Other sites of measurable disease by RECIST v1.1 are present
- •Relevant records of any CNS treatment must be available
排除标准
- •Have previously been treated with:
- •Lapatinib or neratinib within 12 months of starting study treatment (except in cases where lapatinib or neratinib was given for ≤21 days and was discontinued for reasons other than disease progression or severe toxicity)
- •Tucatinib or enrolled on a tucatinib clinical trial
- •Any investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) (eg, afatinib) at any time previously
- •Trastuzumab deruxtecan or another antibody-drug conjugate (ADC) consisting of an exatecan derivative
- •Have received treatment with:
- •Any systemic anti-cancer therapy (including hormonal therapy) or experimental agent ≤21 days of first dose of study treatment or are currently participating in another interventional clinical trial. An exception for the washout of hormonal therapies is gonadotropin releasing hormone (GnRH) agonists used for ovarian suppression in premenopausal women, which are permitted concomitant medications
- •Treatment with non-CNS radiation ≤7 days prior to first dose of study treatment
- •Major surgery <28 days of first dose of study treatment
- •Have clinically significant cardiopulmonary disease (such as history of iterstitial lung disease (ILD)/pneumonitis that required systemic corticosteroids, or have current ILD/pneumonitis, or where suspected ILD /pneumonitis cannot be ruled out be imaging at screening)
- •Have known myocardial infarction or unstable angina within 6 months prior to first dose of study treatment
- •Known to be positive for hepatitis B by surface antigen expression. Known to be positive for hepatitis C infection. Participants who have been treated for hepatitis C infection are permitted if they have documented sustained virologic response of 12 weeks
- •Presence of known chronic liver disease
- •Active or uncontrolled clinically serious infection
- •Have inability to swallow pills or significant gastrointestinal disease which would preclude the adequate oral absorption of medications
研究组 & 干预措施
Single Arm
Experimental
Tucatinib + trastuzumab deruxtecan
干预措施: tucatinib (Drug)
Single Arm
Experimental
Tucatinib + trastuzumab deruxtecan
干预措施: trastuzumab deruxtecan (Drug)
结局指标
主要结局
Confirmed Objective Response Rate (cORR) Per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 According to Investigator (INV) Assessment
时间窗: From the first dose of study treatment until the first documented PD or before start of any new anti-cancer therapy (up to 43 months)
Confirmed objective response rate was defined as the percentage of participants with a confirmed complete response (CR) or partial response (PR) per investigator according to RECIST v1.1. For a response to be considered confirmed, the subsequent response had to be at least 4 weeks after the initial response. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (\<)10 millimeters (mm). PR: a greater than equal to (\>=) 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. 95% exact confidence interval (CI) was based on Clopper-Pearson method.
次要结局
- Progression-Free Survival (PFS) Per RECIST v1.1 According to INV(From the start of study treatment until the first documentation of PD or death due to any cause, whichever occurred first (approximately 46.2 months of treatment exposure))
- Duration of Response (DOR) Per RECIST v1.1 According to INV(From the first documented objective response until the first documentation of PD or death, whichever occurred first (approximately 46.2 months))
- Disease Control Rate (DCR) Per RECIST v1.1(From first dose of study treatment until PD or death, whichever occurred first (approximately 46.2 months))
- Overall Survival (OS)(From date of start of study treatment until date of death or censoring date (approximately 46.2 months))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants With Serious Adverse Events (SAEs)(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants With Treatment Emergent Adverse Events Based on Severity(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants With Treatment Related TEAEs(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants With Treatment Emergent Clinical Laboratory Abnormalities(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants With TEAEs Leading to Dose Modification(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants With TEAEs Leading to Treatment Discontinuation(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
- Number of Participants According to Change From Baseline Categories in Ejection Fraction(Baseline up to 30 days after last dose of study treatment (approximately 47.2 months))
- Number of Participants With Clinically Significant Vital Signs(From first dose of the study treatment (Day 1) up to 30 days after the last dose of study treatment (approximately 47.2 months))
研究者
研究点 (232)
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