This phase I/II clinical trial evaluates if using a radiotracer targeting granzyme B, 64-copper granzyme targeting restricted interaction peptide specific to family member B (64 Cu-GRIP B) with positron emission tomography (PET) imaging can be safe and useful for detecting granzyme B (GrB) in patients with advanced cancers that has spread to nearby tissue or lymph nodes (advanced). Granzyme B (GrB) is a biomarker produced by immune cells in response to immunotherapy, which may highlight tumors that are more likely to respond to treatment. The study population is focused on genitourinary (GU) malignancies, including renal cell and urothelial cancer, two tumor types with high mutational burden and tumor infiltrating lymphocytes compared to other tumor types, and have a predictable response rate at the population level to immune checkpoint inhibitors. The information gained from this trial may allow researchers to develop future trials where 64Cu-GRIP B PET may serve as a biomarker to monitor early response to immunomodulatory therapies which are used to stimulate or suppress the immune system and may help the body fight cancer.
Histologically-confirmed metastatic solid tumor malignancy (3 Male, 3 Female)
Locally advanced or metastatic disease on conventional imaging
Histologically-confirmed metastatic renal cell carcinoma (any histologic sub-type) or urothelial carcinoma
Locally advanced or metastatic disease on conventional imaging
Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.
Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.
Is currently pregnant or breastfeeding.
Parallel
Copper-64 labeled Granzyme B (64Cu-GRIP B)
DrugGiven IV prior to imaging
Positron Emission Tomography (PET)
Procedure/SurgeryImaging procedure
Frequency of treatment-emergent adverse events (Cohort A)
For Cohort A, the frequency and severity of adverse events following 64Cu-GRIP B injection will be descriptively reported, using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Percent of injected activity (Cohort A)
For Cohort A, the tracer kinetics is measured in the organs and total-body, and the % of injected activity for each time point will be recorded for participants in Cohort A. This information is used as input for organ and whole-body effective dose calculation using Organ Level INternal Dose Assessment/EXponential Modeling (OLINDA/EXM). This will provide the data of whole-body effective dose (millisievert (mSv)/megabecquerels (MBq)), and organ doses.
Time to maximum observed concentration (Tmax) (Cohort A)
Pharmacokinetic (PK) parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the time it takes for a drug to reach the maximum concentration (Cmax) after administration of a drug that needs to be absorbed.
Maximum observed concentration (Cmax) (Cohort A)
PK parameters for participants in Cohort A derived from plasma will be calculated using a non-compartmental approach with a log-linear terminal assumption for up to a possible 5 time points. A custom software package or a commercial software package like Phoenix WinNonlin will be used to compute the maximum concentration (Cmax) after administration of a drug that needs to be absorbed.
Frequency of treatment-emergent adverse events (Cohorts B, C, and D)
For Cohorts B, C and D, the frequency and severity of adverse events following 64Cu-GRIP B injection will be descriptively reported
Mean SUVmax in metastatic lesions by disease site (Cohorts B, C and D)
For Cohorts B, C and D, the mead/standard deviation (sd) (median and range, if normality assumption does not hold) for intra-tumoral SUVmax within metastatic lesions will be descriptively reported, to assess for intra-tumoral heterogeneity and differences in uptake by site of disease.
Percent of lesions detected for metastatic participants (Cohorts B, C and D)
For Cohorts B, C and D, the percentage of metastatic lesions detected on conventional imaging that are also detected on baseline 64Cu-GRIP B PET will be descriptively reported with 95% confidence intervals.
Median change in SUVmax from baseline with reported immune-related adverse event (Cohort B)
For the subset of patients in Cohort B experiencing Grade ≥ 2 immune-related adverse event who have 64Cu-GRIP B PET performed within 14 days of onset of event, the mean change from baseline in involved organ site(s) uptake on PET will be descriptively reported along with sd (or median with range) at lesion-level
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Rahul Aggarwal
Lead sponsor
University of California, San Francisco
Sponsor institution
National Cancer Institute (NCI)
Collaborator
U.S. Army Medical Research Acquisition Activity
Collaborator
