This is a single-center, single-arm, investigator sponsored trial designed to evaluate the PK of the anti-CD8 imaging agent in patients prior to and during treatment with checkpoint inhibitors.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
47
An imaging agent radiolabelled with 89Zr developed for in human PET imaging of CD8
University Medical Center Groningen
Groningen, Netherlands
Incidence of adverse events related to tracer administration as assessed by CTCAE v4.0
Safety assessment through summaries of adverse events, changes in laboratory test results (if evaluation is indicated), changes in vital signs, and exposure to ZED88082A/CED88004S. Adverse event data will be recorded and summarized according to NCI CTCAE v4.0.
Time frame: 2 years
Appropriate dosing of anti-CD8 imaging agent and PET imaging time points
Appropriate dosing and imaging time points of the anti-CD8 imaging agent will be determined based on measurements of standardized uptake value (SUV) of defined volumes of interest (VOIs) on the immunoPET scan images
Time frame: 2 years
Pharmacokinetics (PK) of anti-CD8 imaging agent
Description of PK of the anti-CD8 imaging agent by measuring standardized uptake value (SUV) on PET scans performed 0, 2, 4 and/or 7 days after tracer injection before and during MPDL3280A or PD-1 antibody immune checkpoint inhibitor plus or minus ipilimumab treatment.
Time frame: 2 years
Immunogenic potential of the anti-CD8 imaging agent by measuring incidence of anti-drug antibodies
Assessment of the immunogenic potential of the anti-CD8 imaging agent by measuring incidence of anti-drug antibodies during the study relative to the prevalence of ADAs at baseline and assessing their relationship to other outcomes measured.
Time frame: 2 years
Heterogeneity of tumor uptake of the anti-CD8 imaging agent
Heterogeneity of imaging tracer uptake will be evaluated by measuring standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the immunoPETscan images
Time frame: 2 years
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Correlation of normal organ uptake of the anti-CD8 imaging agent to (serious) adverse events (possibly) related to immune checkpoint inhibitor treatment
Normal organ uptake of the anti-CD8 imaging agent as measured by SUVs on PET scan images will be analyzed on correlation to (serious) adverse events (possibly) related to ICI treatment, defined as all (S)AEs which are assessed as "possibly", "probably" or "definitely" related to ICI treatment.
Time frame: 2 years
Correlation of tumor uptake of the anti-CD8 imaging agent and immune cell CD8 expression
Results of immunohistochemical scoring of tumor and immune cell CD8 and other markers of lymphocytic infiltration in fresh biopsies will be described as a semi-quantitative score using the percentage of positive cells (continuous variable), intensity and pattern of staining (discrete variable). These IHC results will be compared with imaging tracer standardized uptake value (SUV) in defined volumes of interest (VOIs) of tumor lesions on the immunoPETscan images. Results of autoradiography will be described by measuring standardized uptake value (SUV) on the biopsy slides.
Time frame: 2 years
Correlation of anti-CD8 imaging agent normal tissue kinetics with blood kinetics
PK parameters will be derived from anti-CD8 imaging agent serum concentrations and will be summarized using descriptive statistics including but not limited to the number of patients, mean, standard deviation, median, minimum and maximum.
Time frame: 2 years
Dosimetry
Assessment of dosimetry will be performed by calculations of radioactivity in Bq or mSv of anti-CD8 imaging agent concentration in tumor target tissue, blood and other organs of interest with regards to injected dose (ID), derived from measurements of standardized uptake value (SUV) on immunoPET images and direct analysis of blood 89Zr-activity.
Time frame: 2 years