A Phase 1 Study of the Antibody-Radionuclide Conjugate SLR-108 for Positron Emission Tomography Imaging in Subjects With Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Optimal antibody protein dose
研究概览
简要总结
This is a Phase 1 study evaluating the feasibility of using SLR-108 for positron-emission tomography (PET) imaging of metastatic solid tumors.
详细描述
This study will assess the safety, pharmacokinetics, biodistribution, radiation dosimetry, and image quality of a single IV injection of the diagnostic radiopharmaceutical SLR-108, evaluating a range of antibody protein dose levels and radioactivity dose levels in subjects with metastatic solid tumors. PET imaging will be performed following administration of SLR-108.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Diagnostic
- 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
- •Men or women (as appropriate for cancer type) of age ≥18 years.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or
- •Histologically or cytologically confirmed diagnosis of solid tumor as documented in medical records.
- •Based on the most recent tumor assessment, presence of metastatic disease that has progressed during or following previous treatment.
- •Presence of radiographically measurable disease (defined as the presence of ≥1 non-osseous tumor lesion that measures ≥10 mm in longest dimension [≥15 mm in shortest dimension for lymph nodes] and is outside of any prior radiation field).
- •Prior receipt of commercially available therapies that are indicated for the subject's cancer and have a demonstrated survival benefit for that indication.
- •Availability of tumor tissue from fresh tumor biopsy obtained by a core needle, excisional, or incisional biopsy; or punch biopsy (for cutaneous disease); or archival sample from a previous biopsy.
- •Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before study drug administration.
- •Adequate hematological profile.
- •Adequate coagulation profile.
- •Adequate hepatic profile.
- •Adequate renal function.
- •Negative viral serology or adequate therapy for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infection.
- •For female subjects of childbearing potential, a negative serum pregnancy test.
- •For female subjects of childbearing potential, willingness to use a protocol recommended method of contraception from the start of the screening period until ≥6 months after study drug administration.
- •For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol recommended method of contraception from the start and until ≥6 months after study drug administration and to refrain from sperm donation from the start and until ≥12 months after study drug administration.
- •Willingness and ability of the subject to comply with scheduled visits, the drug administration plan, protocol-specified laboratory tests, other study procedures (including any required tumor biopsy/aspirations and all radiographic studies), and study restrictions.
- •Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the study drug, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.
排除标准
- •Malignancy involving the central nervous system unless brain metastases have been previously treated with radiotherapy, have been stable for ≥4 weeks, and do not require corticosteroids.
- •Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
- •Uncontrolled ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infection) at the time of study drug administration.
- •Significant cardiovascular event or comorbidity.
- •Significant screening ECG abnormalities.
- •Pregnancy or breastfeeding.
- •Any medical condition preventing PET/CT scanning, and/or inability to tolerate up to 60 minutes of PET/CT scanning per imaging session, and/or ineligibility for PET/CT scanning due to the weight limits of the scanner.
- •Major surgery within 4 weeks before study drug administration.
- •Use of a drug known to prolong the QT interval within 7 days prior to study drug administration.
- •Anticipated use of a strong inhibitor or inducer of cytochrome CYP3A4 or CYP1A
- •Concurrent participation in another therapeutic or imaging clinical trial.
- •Any illness, medical condition, organ system dysfunction, or social situation, including mental illness or substance abuse, deemed by the investigator to be likely to interfere with a subject's ability to provide informed consent, adversely affect the subject's ability to cooperate and participate in the study, or compromise the interpretation of study results.
研究组 & 干预措施
Part 2
TBD total antibody dose, lower TBD radioactivity dose
干预措施: SLX-1411 (Drug)
Part 3
TBD total antibody dose, TBD radioactivity dose
干预措施: SLR-108 (Drug)
Part 1: Cohort 1
Low total antibody dose, initial radioactivity dose
干预措施: SLX-1411 (Drug)
Part 1: Cohort 1
Low total antibody dose, initial radioactivity dose
干预措施: SLR-108 (Drug)
Part 1: Cohort 2
Medium total antibody dose, initial radioactivity dose
干预措施: SLR-108 (Drug)
Part 1: Cohort 2
Medium total antibody dose, initial radioactivity dose
干预措施: SLX-1411 (Drug)
Part 1: Cohort 3
High total antibody dose, initial radioactivity dose
干预措施: SLR-108 (Drug)
Part 1: Cohort 3
High total antibody dose, initial radioactivity dose
干预措施: SLX-1411 (Drug)
Part 2
TBD total antibody dose, lower TBD radioactivity dose
干预措施: SLR-108 (Drug)
Part 3
TBD total antibody dose, TBD radioactivity dose
干预措施: SLX-1411 (Drug)
结局指标
主要结局
Optimal antibody protein dose
时间窗: Through Day 14
The appropriate antibody dose (in mg) for optimal imaging
Optimal administered activity
时间窗: Through Day 14
The appropriate radioactivity dose (in mCi) for optimal imaging
Optimal SLR-108 PET timing
时间窗: Through Day 14
The optimal timing of PET imaging for differentiating tumor tissue from normal background tissue
次要结局
- Study drug administration(Through Day 0)
- Study drug safety(Through Day 14)
- Supportive care profile(Through Day 14)
- Study drug pharmacokinetics - Cmax(Through Day 14)
- Study drug pharmacokinetics - AUC(Through Day 14)
- Study drug pharmacokinetics - t1/2(Through Day 14)
- Image Quality(Through Day 14)
- PET tumor lesion identification(Through Day 14)
- CT tumor lesion identification(Through Day 14)
- Biodistribution(Through Day 14)
- Normal tissue radiation dosimetry(Through Day 14)
- Tumor tissue radiation dosimetry(Through Day 14)
- Immunogenicity(Through Day 14)