NCT07413939招募中2 期
A Two-part, Seamless, Multicenter, Randomized, Open-label, Adaptive Phase II/III Study of the Blood-brain Barrier Penetrant RO7771950 Versus Tucatinib, Both in Combination With Trastuzumab and Capecitabine, in Patients With Pretreated Unresectable Locally Advanced or Metastatic HER2-Positive Breast Cancer, With or Without Central Nervous System Metastases
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 650
- 试验地点
- 193
- 主要终点
- Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR)
研究概览
简要总结
The purpose of this study is to assess the efficacy and safety of RO7771950 in combination with trastuzumab and capecitabine, compared to tucatinib in combination with trastuzumab and capecitabine.
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
- •Pathologically documented locally advanced inoperable (LAI) or metastatic breast cancer (MBC) with confirmed HER2-positive status by central laboratory.
- •Measurable disease as per by RECIST v1.1 in stage
- •Non-measurable disease allowed in stage
- •Previously treated (stable or progressive) or previously untreated CNS metastases, or leptomeningeal metastases.
- •At least one prior line of anti-HER2-based therapy for LAI or metastatic disease.
- •Prior anti-HER2 antibody-drug conjugate (ADC), such as trastuzumab-deruxtecan (T-DXd) or trastuzumab emtansine (T-DM1), in any treatment setting. Participants without prior ADC therapy may only be enrolled if approved standard-of-care (SOC) anti-HER2 ADC is not locally accessible at screening, or if there is a prospectively documented clinical contraindication.
- •Prior tyrosine kinase inhibitor (TKI) in the (neo)adjuvant setting provided completion is > 12 months ahead of LAI occurrence. Prior treatment with TKIs for LAI/MBC is not permitted.
- •Has protocol-defined adequate organ and bone marrow function.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Baseline left ventricular ejection fraction (LVEF) ≥ 50%.
排除标准
- •Concurrent anti-cancer treatment, or treatment with investigational therapy within 28 days prior to initiation of study treatment.
- •Known active/untreated hepatitis B or C or chronic liver disease.
- •Clinically significant cardiovascular disease or risk, including heart failure (New York Heart Association (NYHA) ≥ II), ischemic heart disease or recent coronary events/interventions, clinically significant arrhythmias or electrocardiogram (ECG) abnormalities, QT prolongation or risk of ventricular dysrhythmias, poorly controlled hypertension, peripheral arterial disease, dilated cardiomyopathy, or unstable angina.
- •Clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome.
- •Concomitant use of any drug or herbal medicine known to strongly inhibit or induce CYP3A4 or CYP2C8 activity, oral coumarin-derivative anticoagulants.
研究组 & 干预措施
Arm C - Tucatinib
Active Comparator
干预措施: Capecitabine (Drug)
Arm B - RO7771950 Dose Type 2
Experimental
干预措施: Trastuzumab (Drug)
Arm A - RO7771950 Dose Type 1
Experimental
干预措施: RO7771950 (Drug)
Arm B - RO7771950 Dose Type 2
Experimental
干预措施: RO7771950 (Drug)
Arm C - Tucatinib
Active Comparator
干预措施: Trastuzumab (Drug)
Arm B - RO7771950 Dose Type 2
Experimental
干预措施: Capecitabine (Drug)
Arm C - Tucatinib
Active Comparator
干预措施: Tucatinib (Drug)
Arm A - RO7771950 Dose Type 1
Experimental
干预措施: Capecitabine (Drug)
Arm A - RO7771950 Dose Type 1
Experimental
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Progression-free Survival (PFS) as Determined by Blinded Independent Central Review (BICR)
时间窗: Approximately 35 months
Time from randomization to disease progression or death, according to standard criteria (Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)).
次要结局
- Progression-free Survival in Participants with Central Nervous System Metastases (PFS-CNS) by BICR(Approximately 35 months)
- Objective Response Rate (ORR) by BICR(Approximately 35 months)
- Duration of Response (DOR) as per BICR(Approximately 35 months)
- Clinical Benefit Rate (CBR) as per BICR(Approximately 35 months)
- Health Utility Scores of the European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L)(Approximately 35 months)
- Plasma Concentration of RO7771950 and its Metabolite(s) at Specified Timepoints(Approximately 35 months)
- Change from Baseline in the Columbia-suicide Severity Rating Scale (C-SSRS)(Approximately 35 months)
- Change from Baseline in Echocardiogram (ECHO)/Multiple-gated Acquisition (MUGA)(Approximately 35 months)
- Overall Survival in Full Analysis Set (OS-FAS)(Approximately 53 months)
- Incidence of Adverse Events (AEs)(Approximately 35 months)
- ORR in Participants with CNS Metastases (ORR-CNS)(Approximately 35 months)
- DOR in Participants with CNS Metastases (DOR-CNS)(Approximately 35 months)
- CBR in Participants with CNS Metastases (CBR-CNS)(Approximately 35 months)
- Changes from Baseline in Symptoms Burden in Participants With Brain Tumors(Approximately 35 months)
- Changes from Baseline in Function and Health-related Quality of Life (HRQoL)(Approximately 35 months)
- Severity of AEs(Approximately 35 months)
- Number of Participants Reporting Presence, Frequency of Occurrence, Severity, and/or Degree of Interference With Daily Activities of Symptomatic Treatment Toxicities as Assessed Through Use of the Patient-reported Outcome (PRO)-CTCAE(Approximately 35 months)
- Proportion of Participants Reporting Each Response Option at Each Assessment Timepoint by Treatment Arm for Treatment Side-effect Bother Single-item Functional Assessment of Cancer Therapy (FACT-GP5)(Approximately 35 months)
- Change from Baseline/Worsening in Symptomatic Treatment Toxicities as Assessed Through Use of the PRO-CTCAE(Approximately 35 months)
- Change from Baseline/Worsening in Symptomatic Treatment Side-effect Bother FACT-GP5(Approximately 35 months)
研究者
研究点 (193)
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