Phase 1 Study of 68Ga-R11228 and 177Lu-R11228 in Patients With Advanced Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 11
- 试验地点
- 9
- 主要终点
- Incidence of Serious Adverse Events [177Lu-R11228]
研究概览
简要总结
A phase 1 study of 68Ga-R11228 and 177Lu-R11228 in breast cancer.
详细描述
Patients with metastatic or locoregionally recurrent ER+ and/or PR+ and HER2 negative breast cancer will be enrolled.
Part A is being conducted to test 68Ga-R11228, a new investigational product (IP) that has been designed to detect cancer lesions in the body and make them visible on a Positron Emission Tomography (PET) scan. Three dose levels of 68Ga-R11228 will be evaluated, with each patient receiving a single dose.
Part B is being conducted to test 68Ga-R11228 and additionally 177Lu-R11228, which has been designed to treat patients who have cancer lesions with positive uptake on PET scan using 68Ga-R11228. Patients who qualify for 177Lu-R11228 treatment will receive up to 6 doses over approximately 36 weeks. Multiple 177Lu-R11228 dose levels will be evaluated in Part B.
A 5-year Follow-Up Period begins once the last cycle of 177Lu-R11228 dosing is completed.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed estrogen and/or progesterone receptor (ER/PR) positive and HER2 negative locoregionally recurrent or metastatic breast cancer
- •At least one target or non-target lesion per RECIST v1.1 criteria.
- •Male or non-pregnant, non-lactating female subjects age ≥18 years.
- •Pathologically confirmed estrogen and/or progesterone receptor (ER/PR) positive and HER2 negative locoregionally recurrent or metastatic breast cancer
- •Refractory to endocrine therapy. Note: there is no limit on prior number of lines of endocrine therapy or prior treatments with CDK4/6, AKT, PI3K and/or mTOR inhibitors.
- •Received or declined at least one line of chemotherapy or antibody drug conjugate in the locoregionally recurrent or metastatic setting
- •Progressive disease or intolerance to last treatment.
- •At least one target lesion per RECIST v1.1 criteria.
- •Male or non-pregnant, non-lactating female subjects age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or
- •Life expectancy of at least six months.
- •Adequate bone marrow reserve, hepatic function and renal function.
排除标准
- •Study participant has not recovered from clinically significant adverse event(s) resulting from most recent anticancer therapy/intervention.
- •Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period.
- •Radiotherapy for breast cancer ≤ 28 days prior
- •Received a radionuclide within a period of less than 10 physical half-lives of the administered radionuclide prior to dosing with 68Ga-R
- •Any condition that precludes the proper performance of imaging procedures required in this study.
- •Study participant has not recovered from clinically significant adverse event(s) resulting from most recent anticancer therapy/intervention
- •Treatment with anticancer therapy or with an investigational drug or device within 21 days or 5 half-lives of the agent (whichever is shorter)
- •Known central nervous system (CNS) disease, except for those subjects with treated brain metastasis who are stable for at least 1 month, having no evidence of progression or hemorrhage after treatment and no ongoing requirement for corticosteroids, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT]) during the screening period.
- •Radiotherapy for breast cancer ≤ 28 days
- •Prior systemic radionuclide therapeutic treatment.
- •Received a radionuclide within a period of less than 10 physical half-lives of the administered radionuclide prior to dosing with 68Ga-R
- •Any unresolved NCI-CTCAE Version 5.0 Grade 2 or higher toxicity (except alopecia and Grade 2 platinum-therapy related neuropathy) from previous breast cancer treatment and/or from medical/surgical procedures or interventions.
- •Any condition that precludes the proper performance of imaging procedures required in this study.
研究组 & 干预措施
Part B: 68Ga-R11228 Imaging and 177Lu-R11228 Dose Ranging Portion
68Ga-R11228 injection at pre-defined dose. 177Lu-R11228 injection at pre-defined doses.
干预措施: 68Ga-R11228 (Drug)
Part A: 68Ga-R11228 Dose Optimization Portion
68Ga-R11228 injection at pre-defined dose levels.
干预措施: 68Ga-R11228 (Drug)
Part B: 68Ga-R11228 Imaging and 177Lu-R11228 Dose Ranging Portion
68Ga-R11228 injection at pre-defined dose. 177Lu-R11228 injection at pre-defined doses.
干预措施: 177Lu-R11228 (Drug)
结局指标
主要结局
Incidence of Serious Adverse Events [177Lu-R11228]
时间窗: Day 1 to week 36
Number of participants with serious adverse events
Incidence of adverse events [68Ga-R11228]
时间窗: Day 1 to Day 7
Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade
Incidence of Serious Adverse Events [68Ga-R11228]
时间窗: Day 1 to Day 7
Number of participants with serious adverse events
Incidence of adverse events [177Lu-R11228]
时间窗: Day 1 to week 36
Number of participants with adverse events as assessed by NCI-CTCAE v5.0, including grade
Incidence of dose limiting toxicities [177Lu-R11228]
时间窗: Day 1 to week 36
Number of participants with dose limiting toxicities
次要结局
- Standardized uptake value in tumor lesions [68Ga-R11228](Day 1)
- Image quality(Day 1)
- Absorbed dose coefficients [68Ga-R11228](Day 1)
- Effective whole-body dose for 68Ga-R11228(Day 1)
- Inter-reader agreement(Day 1)
- Number of study participants with at least one tumor lesion detected(Day 1)
- Intra-reader reproducibility(Day 1)
- Proportion of tumor lesions detected by imaging with 68Ga-R11228 per study participant(Day 1)
- Absorbed dose coefficients [177Lu-R11228](7 days)
- Objective response rate(36 weeks)
- Duration of response(36 weeks)
- Progression free survival(36 weeks)
- Overall survival(36 weeks)
- Pharmacokinetic parameters of 68Ga-R11228(Day 1)
- Pharmacokinetic parameters of 177Lu-R11228(7 days)