A Pilot Study of [18F]F-AraG Pharmacokinetics in Tumors and Non-Malignant Tissue Using Dynamic Total Body PET Imaging in Healthy Subjects and in Patients With Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues
研究概览
简要总结
In this pilot study, healthy volunteers and patients with Non-Small Cell Lung Cancer will undergo [18F]F-AraG dynamic imaging on the uEXPLORER total body Positron Emission Tomography/Computerized Tomography scanner to obtain preliminary data regarding pharmacokinetics and early biodistribution images.
详细描述
[18F]F-AraG, a fluorine-18 labeled analog of an FDA approved drug (Nelarabine) is a new imaging tracer targeted at imaging activated T-cells. Given that immunotherapeutic strategies, in particular immune checkpoint antibodies, focus on the generation of T-cell-based antitumor immunity, uptake of [18F]F-AraG within the tumor is hypothesized to correlate with T-cell mediated immune response seen in the biopsy samples of cancer patients treated with immune checkpoint blockade. Correlation of pre- and post-treatment intratumoral immune infiltration by means of PET imaging will guide the development of future clinical trials investigating the role of [18F]F-AraG in the monitoring of anti-tumor immune responses. Therefore, proper quantification of [18F]F-AraG uptake in tumor lesions, and understanding its relation with physiologic uptake in background tissues is important. Note: checkpoint therapy in this study is standard-of-care and is not under investigation.
Available PET/CT scanners can obtain dynamic images only on a portion of the body as large as their axial field of view, generally anywhere between 15-30 cm. The 194 cm long uEXPLORER total-body PET scanner is the world's first device to offer the ability to tomographically image all parts of the body simultaneously. Thus, the uEXPLORER PET/CT (now commercially available and with FDA 510(k) clearance) is the only scanner in the world capable of acquiring total-body dynamic images.
In this pilot study, 2-4 healthy volunteers will undergo [18F]F-AraG dynamic imaging on the uEXPLORER total body PET/CT scanner to obtain preliminary data regarding pharmacokinetics and early biodistribution images. In addition, 2-4 patients with NSCLC and planned for standard-of-care PD-1/PD-L1 immunotherapy will undergo [18F]F-AraG dynamic imaging similarly on the uEXPLORER total body PET/CT scanner to obtain data regarding pharmacokinetics of the tracer in tumor lesions in the context of normal tissue uptake. An optional second similar scan will be performed 7-14 days after the first dose of immunotherapy to explore and document any treatment related changes in [18F]F-AraG uptake and kinetics.
The study and data collected will be important to recommend an ideal time to acquire a whole body static scan using conventional and widely available PET/CT scanners for adequate tumor to background contrast and quantification, which in turn, will be essential for further clinical development of [18F]F-AraG to aid the monitoring of anti tumor immune responses.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Basic Science
- 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
- 是
入选标准
- •Age ≥ 18 years.
- •Ability to understand the purposes and risks of the trial and has signed an IRB-approved informed consent form.
- •Willingness and ability to comply with all protocol required procedures.
- •For men and women of child-producing potential, willingness to use of effective double barrier contraceptive methods during the study, up to 1 day after the last administration of the investigational product.
- •For NSCLC subjects only:
- •Patients with histologically confirmed advanced, locally advanced, or localized NSCLC.
- •Planned to undergo treatment with a PD-1 or PD-L1 inhibitor either as 1) monotherapy or as combination therapy with concurrent chemotherapy as treatment for advanced/metastatic disease; 2) As consolidation therapy following chemoradiation for locally advanced disease or 3) As induction therapy either as monotherapy or combination therapy with chemotherapy prior to planned surgical resection
- •At least 1 tumor lesion > 1 cm (cannot be only in liver) documented on CT or MRI or FDG-PET/CT (RECIST criteria 1.1; >1.5 cm for nodal lesions) within 45 days prior to scan date.
- •Per investigator's assessment and in consultation with oncologists, at least one eligible lesion must be sufficiently separated from tissues with known high [18F]F-AraG uptake, such as salivary glands, bladder, liver and kidneys so that quantification will be feasible.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Meeting all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment.
排除标准
- •Subjects are not eligible if they meet ANY of the following criteria:
- •Serious comorbidities (nonmalignant disease or other conditions) that in the opinion of the investigator could compromise protocol objectives.
- •History of recent COVID-19 infection within the last 2 months OR history of COVID requiring hospitalization with lung injury at Investigator's discretion
- •Subjects with a diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the scan
- •Subjects receiving therapy with nucleoside analogs including but not limited to: acyclovir, valaclovir, penciclovir, famciclovir, ganciclovir, ribavirin, valganciclovir, glanciclovir
- •Pregnant women or nursing mothers.
- •Body weight more than 240 kg (529 pounds)
- •For NSCLC subjects only:
- •Prior Treatment with anti-PD-1/PD-L1 immunotherapy.
- •For Healthy subjects
- •No primary care physician
研究组 & 干预措施
Healthy Volunteers
Study participants will undergo a single dynamic [18F]F-AraG PET/CT scan (of duration up to 90-minutes) on the uEXPLORER PET/CT scanner. There will be a follow-up visit or call 7 days after the scan to assess any adverse events that could be attributed to either the scan or the administration of [18F]F-AraG.
干预措施: [18F]F-AraG Imaging (Drug)
Non-Small Cell Lung Cancer Patients (NSCLC)
Study participants with NSCLC who are planned to receive PD-1/PD-L1 immunotherapy will undergo a pre-therapy dynamic [18F]F-AraG PET/CT scan, and an optional post-therapy (first dose only) dynamic [18F]F-AraG PET/CT scan on the uEXPLORER total-body scanner.
干预措施: [18F]F-AraG Imaging (Drug)
结局指标
主要结局
Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues
时间窗: Baseline
Data on \[18F\]F-AraG uptake in several tissue types will be collected from healthy subjects. This data will be presented in the form of time-activity curves (TAC) generated for each tissue type. Quantitative assessment of \[18F\]F-AraG biodistribution in healthy tissues will be reported as a function of time as mean Standard Uptake Value (SUV)
Data on Whole-body Pharmacokinetics of [18F]F-AraG Pathologic Uptake in Tumor Lesions Relative to Uptake in Background Tissues in NSCLC Subjects
时间窗: Baseline and 7-14 days after first dose of PD-1/PD-L1
Data on \[18F\]F AraG uptake in tumor lesions and background activity in the same tissues as in Outcome 1 will be collected. This data will be similarly presented in the form of time-activity curves (TAC) generated for each tissue type, as well as for tumor lesions against their background tissues.
Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake
时间窗: Baseline and 7-14 days after first dose of PD-1/PD-L1
We will calculate the tumor-to-background Standardized Uptake Value Ratio (SUVR) at multiple time points. The primary aim is to identify the earliest time at which the SUVR indicates adequate tumor uptake relative to non-malignant tissue. This will guide recommendations for the ideal imaging start time for static whole-body scans.
次要结局
未报告次要终点
研究者
Simon R. Cherry
Professor
University of California, Davis