An Open Label Positron Emission Tomography (PET) Imaging Study Using 89Zirconium to Investigate the Biodistribution of Anti-HER3 Monoclonal Antibody (mAb) GSK2849330 and Characterize Its Dose-receptor Occupancy Relationship in Subjects With Advanced HER3-Positive Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Standardized Uptake Value (SUV).
研究概览
简要总结
Human epidermal growth factor receptor 3 (HER3) expression is seen across a wide variety of solid malignancies and is associated with poor prognosis. Up-regulation of HER3 expression and activity is also associated with resistance to multiple pathway inhibitors. GSK2849330, a monoclonal antibody (mAb) targeting HER3, is a new agent for subjects whose tumors express HER3. This study aims to characterise the biodistribution and dose-receptor occupancy relationship of GSK2849330 in patients with advanced HER3 expressing solid tumours via the use of PET imaging. This study will be conducted in two parts. Part 1 will be the imaging phase where each subject will receive two doses of GSK2849330 containing both Zirconium-89 (89Zr) labelled GSK2849330 and unlabeled GSK2849330. The amount of unlabeled GSK2849330 present in each dose will be varied to explore the effect on target mediated uptake of 89Zr into HER3 expressing tissues and tumors. Subjects will then proceed to the continuation phase (Part 2) for continued treatment with unlabelled GSK2849330. The study is planned to enroll approximately 12-15 subjects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- 未提供
排除标准
- •Subjects with leptomeningeal or brain metastases or spinal cord compression
- •Prior HER3- directed treatment (HER2- or EGFR-directed treatment is acceptable).
- •Unresolved toxicity greater than National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE), version 4.0 Grade 1 from previous anti-cancer therapy
- •Known or suspected hypersensitivity reaction to prior biologic therapy
- •Evidence of another active malignancy (excludes non-melanoma skin cancer).
- •Concurrent medical condition that would jeopardize compliance with the protocol.
- •Receiving concurrent anti-tumor therapies, or chronic immunosuppressive therapies (includes daily steroid doses in excess of 20 milligram (mg)/day of prednisolone).
研究组 & 干预措施
Imaging Phase + Continuation Phase
In Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.
干预措施: GSK2849330 (Drug)
Imaging Phase + Continuation Phase
In Part 1 of the study, participants will receive a dose of 89Zr-GSK2849330 (Dose 1), with an activity of no more than 37 MegaBequerel (MBq) and a variable total dose of GSK2849330. PET scans will be acquired within 7 days. Two weeks after Dose 1 participants will receive second dose of 89Zr-GSK2849330 (Dose 2) and a variable total dose of GSK2849330. Participants will continue to receive unlabelled GSK2849330 (in Part 2) either at established dose level or as decided by medical monitor.
干预措施: 89Zr-GSK2849330 (Drug)
结局指标
主要结局
Standardized Uptake Value (SUV).
时间窗: Up to Day 21
Regions of interest (RoI) will be outlined from PET-CT images to represent the tissue radioactivity concentration through the values of SUVmean and SUVpeak.
Volume of region of interest.
时间窗: Up to Day 21
RoIs will be outlined to represent whole organs and include the volumes encircled
次要结局
- Average radioactivity concentration in whole blood and plasma(Up to Day 21)
- Tumor features assessment(Up to Day 21)
- Composite of pharmacokinetic (PK) parameters of GSK2849330(Predose, and at 1, 3, 6, 12 and 24 hours post dose.)
- Organ dose measured in milliSievert (mSv) for each organ(Up to Day 21)
- Effective dose value measured in mSv(Up to Day 21)
- Overall incidence of Adverse events (AEs) and Serious Adverse events (SAEs)(Average of 6 months)
- Change from baseline in laboratory parameters(Baseline and up to 6 months)
- Anatomical localization of radiolabel.(Up to Day 21)
- Uptake of-GSK2849330 in tumors using pharmacometric model(Up to Day 21)
- Change in uptake parameters in response to the dose difference between dose 1 and 2.(Up to Day 21)
- Left ventricular ejection fraction (LVEF) assessment(Average of 6 months)
- Vital signs monitoring.(Average of 6 months)
- Serum titer of the anti-GSK2849330 antibodies.(Average of 6 months)