A First-in-Human Phase 1, Open-label, Two-stage, Randomized Trial to Assess the Safety, Tolerability, and Biodistribution of [177Lu]Lu-ABY-271 in Tumors and Critical Organs in Subjects With HER2-positive Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 21
- 试验地点
- 3
- 主要终点
- Treatment emergent adverse events
研究概览
简要总结
This is a FiH phase 1, open-label, two-stage, randomized trial to assess the safety, tolerability, and biodistribution of [177Lu]Lu-ABY-271 in subjects with HER2 positive metastatic breast cancer.
详细描述
The trial consists of two parts:
Part A in which the uptake of [177Lu]Lu-ABY-271 in tumors and critical organs will be evaluated and up to 6 subjects will be enrolled sequentially.
Part B in which the optimal protein mass dose range (mg) to be utilized in subsequent clinical trials will be evaluated. 15 subjects will be randomized to 3 different protein mass dose levels (1:1:1), divided into two sequential cohorts with different radioactivity levels.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Subject has unresectable locally advanced or metastatic breast cancer
- •Subject with histologically or cytologically confirmed carcinoma with documented HER2 overexpression (biopsy not older than 2 years): immunohistochemistry (IHC) score 3+; OR 2+ and fluorescence in situ hybridization (ISH) positive
- •At least one known tumor lesion ≥ 15 mm
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Part A only
- •- Subject is in treatment, or planned to start a new line of standard systemic anti-tumor therapy
- •Part B only
- •Subject has progressive disease, documented radiologically in the last three months
- •Subject has received at least 3 lines of standard systemic anti-tumor therapy in the palliative setting
- •Subject has received last dose of previous line of systemic anti-tumor therapy, and has no ongoing treatment related toxicities > grade 1 (except alopecia) prior to planned first dose of [177Lu]Lu-ABY-271
排除标准
- •Active brain metastases
- •Administration of another IMP within 5 half-lives (for experimental biologics: 6 months or 5 half-lives, whichever is longer) of the planned first dose of [177Lu]Lu-ABY-271
- •Exposure to any anti-tumor therapy since the last documented progression, including any radiotherapy within 7 days prior to the planned first dose of [177Lu]Lu-ABY-271
研究组 & 干预措施
Part A
[177Lu]Lu-ABY-271
干预措施: [177Lu]Lu-ABY-271 (Drug)
Part B - Cohort 1
[177Lu]Lu-ABY-271 with protein mass dose A
干预措施: [177Lu]Lu-ABY-271 (Drug)
Part B - Cohort 2
[177Lu]Lu-ABY-271 with protein mass dose B
干预措施: [177Lu]Lu-ABY-271 (Drug)
Part B - Cohort 3
[177Lu]Lu-ABY-271 with Protein mass dose C
干预措施: [177Lu]Lu-ABY-271 (Drug)
结局指标
主要结局
Treatment emergent adverse events
时间窗: From baseline to the end-of-trial visit, for part A Day 29 and for part B Day 43
Dose Limiting Toxicities
时间窗: From baseline to the end-of-trial visit, for part A Day 29 and for part B Day 43
次要结局
- Absorbed dose coefficient (Gy/GBq) per organ and selected tumors(From baseline to day 8)
- Normalized whole-body effective dose (millisieverts [mSv]/MBq)(From baseline to day 8)
- Absorbed dose in gray (Gy) per organ and selected tumors(From baseline to day 8)