Lung Cancer, Nonsmall Cell
Conditions
Keywords
total body positron emission tomography
Brief summary
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.
Detailed description
\[18F\]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.
Interventions
DRUG[18F]F-AraG Imaging
Total body PET imaging using \[18F\]F-AraG
Sponsors
CellSight Technologies, Inc.
University of California, Davis
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Intervention model description
Healthy volunteers and patients with non-small cell lung cancer will undergo identical total-body PET scans. Lung cancer patients will undergo an additional PET scans after starting treatment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
1. Age ≥ 18 years. 2. Ability to understand the purposes and risks of the trial and has signed an IRB-approved informed consent form. 3. Willingness and ability to comply with all protocol required procedures. 4. 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: 5. Patients with histologically confirmed advanced, locally advanced, or localized NSCLC. 6. 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 7. 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. 8. 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. 9. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 10. Meeting all clinical safety lab values per institution's standard of care, or Investigator's discretion, for patients receiving cancer treatment.
Exclusion criteria
Subjects are not eligible if they meet ANY of the following criteria: 1. Serious comorbidities (nonmalignant disease or other conditions) that in the opinion of the investigator could compromise protocol objectives. 2. History of recent COVID-19 infection within the last 2 months OR history of COVID requiring hospitalization with lung injury at Investigator's discretion 3. 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 4. Subjects receiving therapy with nucleoside analogs including but not limited to: acyclovir, valaclovir, penciclovir, famciclovir, ganciclovir, ribavirin, valganciclovir, glanciclovir 5. Pregnant women or nursing mothers. 6. Body weight more than 240 kg (529 pounds) For NSCLC subjects only: 7. Prior Treatment with anti-PD-1/PD-L1 immunotherapy. For Healthy subjects 8. No primary care physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | 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 | 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 | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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.
\[18F\]F-AraG Imaging: Total body PET imaging using \[18F\]F-AraG | 4 |
| 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.
\[18F\]F-AraG Imaging: Total body PET imaging using \[18F\]F-AraG | 1 |
| Total | 5 |
Baseline characteristics
| Characteristic | Healthy Volunteers | Non-Small Cell Lung Cancer Patients (NSCLC) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 1 Participants | 4 Participants |
| Age, Continuous | 58 years STANDARD_DEVIATION 46 | 53 years STANDARD_DEVIATION 0 | 55 years STANDARD_DEVIATION 0 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 1 Participants | 5 Participants |
| Sex: Female, Male Female | 3 Participants | 0 Participants | 3 Participants |
| Sex: Female, Male Male | 1 Participants | 1 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 1 |
| other Total, other adverse events | 0 / 4 | 0 / 1 |
| serious Total, serious adverse events | 0 / 4 | 0 / 1 |
Outcome results
Primary
Data on Whole-body Pharmacokinetics of [18F]F-AraG Pathologic Uptake in Tumor Lesions Relative to Uptake in Background Tissues in NSCLC Subjects
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.
Time frame: Baseline and 7-14 days after first dose of PD-1/PD-L1
Population: Mean and standard deviations are reported across seven different tumor sites and four different lymph nodes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Pathologic Uptake in Tumor Lesions Relative to Uptake in Background Tissues in NSCLC Subjects | Tumor (baseline) | 2.14 SUV | Standard Deviation 0.2 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Pathologic Uptake in Tumor Lesions Relative to Uptake in Background Tissues in NSCLC Subjects | Tumor (after therapy) | 2.30 SUV | Standard Deviation 0.54 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Pathologic Uptake in Tumor Lesions Relative to Uptake in Background Tissues in NSCLC Subjects | Mediastinal Lymph Nodes (Baseline) | 2.54 SUV | Standard Deviation 0.69 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Pathologic Uptake in Tumor Lesions Relative to Uptake in Background Tissues in NSCLC Subjects | Mediastinal Lymph Nodes (after therapy) | 3.15 SUV | Standard Deviation 0.58 |
Primary
Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues
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)
Time frame: Baseline
Population: This outcome measure is only measured in the healthy subjects.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Blood Pool | 0.31 SUV | Standard Deviation 0.01 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Myocardium | 4.36 SUV | Standard Deviation 0.27 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Brain | 0.04 SUV | Standard Deviation 0.01 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Kidney | 32.88 SUV | Standard Deviation 5.42 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Liver | 16.05 SUV | Standard Deviation 2.03 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Spleen | 3.46 SUV | Standard Deviation 0.41 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Muscle | 1.05 SUV | Standard Deviation 0.26 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Lungs | 0.67 SUV | Standard Deviation 0.12 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Bone Marrow | 1.46 SUV | Standard Deviation 0.23 |
| Healthy Volunteers | Data on Whole-body Pharmacokinetics of [18F]F-AraG Physiologic Uptake in Various Healthy Tissues | Lymph Nodes | 1.57 SUV | Standard Deviation 0.51 |
Primary
Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake
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.
Time frame: Baseline and 7-14 days after first dose of PD-1/PD-L1
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Lungs | 1.83 SUV to blood ratio (SUVR) | Standard Deviation 0.37 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Bone Marrow | 4.87 SUV to blood ratio (SUVR) | Standard Deviation 1.04 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Mediastinal Lymph Nodes | 5.68 SUV to blood ratio (SUVR) | Standard Deviation 1.33 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Myocardium | 13.72 SUV to blood ratio (SUVR) | Standard Deviation 0.75 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Tumor | NA SUV to blood ratio (SUVR) | — |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Liver | 54.75 SUV to blood ratio (SUVR) | Standard Deviation 12.38 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Brain | 0.13 SUV to blood ratio (SUVR) | Standard Deviation 0.03 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Spleen | 11.60 SUV to blood ratio (SUVR) | Standard Deviation 1.73 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Muscle | 3.04 SUV to blood ratio (SUVR) | Standard Deviation 0.2 |
| Healthy Volunteers | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Kidney | 109.55 SUV to blood ratio (SUVR) | Standard Deviation 28.88 |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Brain | 0.07 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Liver | 76.5 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Bone Marrow | 4.41 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Kidney | 133.0 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Myocardium | 16.9 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Mediastinal Lymph Nodes | 8.59 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Muscle | 3.93 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Spleen | 11.7 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Tumor | 4.79 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - Pre-Therapy Scan | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Lungs | 1.65 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Tumor | 6.02 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Myocardium | 12.3 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Brain | 0.06 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Kidney | 150.2 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Liver | 67.4 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Spleen | 10.2 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Muscle | 1.90 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Lungs | 1.76 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Bone Marrow | 4.11 SUV to blood ratio (SUVR) | — |
| Non-Small Cell Lung Cancer Patients (NSCLC) - 7 to 14 Days Post Therapy | Tumor-to-Background SUVR Over Time to Determine Earliest Adequate Uptake | Mediastinal Lymph Nodes | 9.50 SUV to blood ratio (SUVR) | — |