A Phase 1b/2a Study of the Combination of KD019 and Trastuzumab in Subjects With HER2-Positive Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 17
- 试验地点
- 6
- 主要终点
- Safety and Tolerability: Percentage of Subjects With Serious Adverse Event (SAE) Related to Tesevatinib
研究概览
简要总结
Evaluate the safety and tolerability and determine the maximum tolerated dose (MTD) of the combination of tesevatinib and trastuzumab in subjects with HER2-positive metastatic breast cancer
详细描述
This is a multicenter, Phase 1b/2a, multiple ascending-dose, open-label study designed to assess the safety, tolerability, and efficacy of tesevatinib (KD019) in combination with trastuzumab in subjects with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. The study planned to include a Phase 2a expansion in which approximately 50 subjects would receive tesevatinib at the maximum tolerated dose (MTD) dose determined in Phase 1b.
The study employs a successive cohort dose-escalation designed to determine the MTD of tesevatinib in combination with trastuzumab. The MTD dose is defined as the dose level below in which : (a) 2 of 3 subjects (or 2 of 6 subjects if Grade ≥ 3 tesevatinib related treatment emergent adverse event [TEAE] experience in 1 of the first 3 subjects).
In the Phase 1b portion of the study, tesevatinib is to be administered orally (PO) to successive cohorts of subjects at 150 mg, 250 mg, 300 mg, 350 mg, and 400 mg once daily (QD).
The following 4 dossing cohorts are initiated during the study:
- Cohort 1: 150 mg tesevatinib PO QD
- Cohort 2: 250 mg tesevatinib PO QD
- Cohort 3: 300 mg tesevatinib PO QD
- Cohort 4: 350 mg tesevatinib PO QD
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- Female
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 250 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Tesevatinib (Drug)
Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 150 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Tesevatinib (Drug)
Arm 1: Tesevatinib 150 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 150 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Trastuzumab (Drug)
Arm 2: Tesevatinib 250 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 250 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Trastuzumab (Drug)
Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 300 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Tesevatinib (Drug)
Arm 3: Tesevatinib 300 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 300 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Trastuzumab (Drug)
Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 350 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Tesevatinib (Drug)
Arm 4: Tesevatinib 350 mg PO QD + Trastuzumab 8 mg/kg IV
Tesevatinib in combination with Trastuzumab: tesevatinib 350 mg PO QD in combination with trastuzumab 8 mg/kg IV initially then 6 mg/kg IV every 3 weeks thereafter.
干预措施: Trastuzumab (Drug)
结局指标
主要结局
Safety and Tolerability: Percentage of Subjects With Serious Adverse Event (SAE) Related to Tesevatinib
时间窗: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up
Percentage of subjects with at least 1 serious adverse event considered related to study drug. SAEs were considered related to tesevatinib drug if the investigator assessed them as possibly related, probably related, or related.
Safety and Tolerability: Percentage of Subjects With Treatment Emergent Adverse Events (TEAEs) by Severity and/or Relationship to Tesevatinib
时间窗: Up to 8 months: 1 month (28 days) Screening + 6 months treatment + 1 month follow-up
Percentage of subjects with at least 1 treatment-emergent adverse event of Grade 3 or greater or relationship with tesevatinib. TEAE grading was by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) where Grade 3 is severe and Grade 4 is life-threatening. TEAEs were considered related to study drug if the investigator assessed them as possibly related, probably related, or related.
次要结局
- Pharmacokinetics: Mean AR Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab(PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1)
- Pharmacokinetics: Median Serum Tmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab(PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1)
- Pharmacokinetics: Mean Serum AUC(0-t) (Area Under Curve) of Treatment With Tesevatinib + Trastuzumab(PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1)
- Pharmacokinetics: Mean AR AUC(0-24hr) After 1 Cycle of Treatment With Tesevatinib + Trastuzumab(PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1)
- Pharmacokinetics (PK): Mean Serum Cmax After 1 Cycle of Treatment With Tesevatinib + Trastuzumab(PK samples taken pre-dose, and 1, 2, 4, 6, 8, and 24 hours post-dose on Cycle 1 Day 1 and Cycle 2 Day 1)