A Phase 2 Study of Poziotinib in Patients With HER2-Positive Metastatic Breast Cancer (MBC) Who Have Received Prior HER2 Regimens for MBC
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 35
- 主要终点
- Objective Response Rate (ORR)
研究概览
简要总结
The purpose of this study is to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.
详细描述
This is a phase 2, open-label, multicenter study to establish the dose regimen and evaluate the preliminary efficacy and the safety/tolerability of poziotinib in participants with HER2-positive metastatic breast cancer who have received at least two prior HER2-directed treatment regimens.
Each treatment cycle will be 21 days in duration. During each 21-day cycle, participants who are eligible for participation will receive poziotinib orally once daily.
All treated participants will be followed up until disease progression, death, intolerable adverse events or up to a maximum of 24 months whichever comes earlier.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histopathologically confirmed primary breast cancer with metastatic lesions.
- •Confirmed HER2 overexpression or gene-amplified tumor
- •At least two prior HER2-directed therapy regimens for breast cancer, including trastuzumab and trastuzumab emtansine
- •Measurable disease per Response Evaluation Criteria for Solid Tumors version 1.1 (RECIST v1.1)
- •Participant is at least 18, and ≤90 years of age.
- •Adequate hematologic, hepatic, and renal function
- •Eastern Cooperative Oncology Group (ECOG) performance status <= 2
排除标准
- •Previous treatment with poziotinib prior to study participation
- •Brain metastases that are symptomatic or require therapy to control symptoms, as well as any history of radiation, surgery, or other therapy, including steroids, to control symptoms from brain metastases within 15 days of enrollment.
- •Anticancer chemotherapy, biologics, immunotherapy, cure-intent radiotherapy, or investigational treatment within 15 days, except for hormone therapy, palliative therapy, or supportive therapy.
- •History of congestive heart failure Class III/IV according to the New York Heart Association (NYHA) Functional Classification or serious cardiac arrhythmias requiring treatment.
- •Cardiac ejection fraction <50%
- •History of other malignancies within the last 5 years
- •Participant is pregnant or breast-feeding.
- •Unable to take drugs orally
研究组 & 干预措施
Cohort 2: Poziotinib 16 mg
Participants received poziotinib 16 mg, administered as two 8 mg tablets, orally, QD, on a continuous dosing schedule in a 21-day cycle until disease progression, death, intolerable AEs or for up to a maximum of 24 months, whichever occurs first.
干预措施: Poziotinib (Drug)
Cohort 1: Poziotinib 24 mg
Participants received poziotinib 24 milligrams (mg), administered as three 8 mg tablets, orally, once daily (QD) on an intermittent dosing schedule of 14 days on treatment followed by 7 days off treatment, in a 21-day cycle until disease progression, death, intolerable adverse events (AEs) or for up to a maximum of 24 months, whichever occurs first.
干预措施: Poziotinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR)
时间窗: Up to 24 months
ORR was defined as the percentage of participants whose best overall response (BOR) was complete response (CR) or partial response (PR) among participants in the Evaluable Population assessed per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). ORR was based on investigator assessed BOR. Per RECIST v1.1 for target lesions, CR was disappearance of all target tumor lesions (TLs) and all target lymph nodes (LNs) with short axis \<10mm. PR was ≥30% decrease in sum of diameters (SOD) from Baseline, and not progressive disease (PD) (≥20% increase in SOD from previous smallest SOD on study, and an absolute increase of ≥5mm).
次要结局
- Time to Progression (TTP)(Up to 24 months)
- Number of Participants With One or More Treatment-Emergent Adverse Events (TEAEs)(From the first dose of study drug administration until 35 (± 5) days after the last dose of study drug administration (Up to approximately 25 months))
- Pharmacokinetic Analysis (Drug Concentration Measurements)(For Cohort 1: Pre-dose and 1 and 2 hours post-dose on Day 1 of Cycles 1, 2, and 3, and pre-dose on Day 14 of Cycle 1 For Cohort 2: Day 1 of Cycle 1 pre-dose and 30 minutes, 1,1.5,2,3, 4, 6, and 24 hours post-dose of Day 1 of Cycle 1)
- Progression Free Survival (PFS)(Up to 24 Months)
- Disease Control Rate (DCR)(Up to 24 months)
- Duration of Response (DoR)(Up to 24 months)