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.
PRIMARY OBJECTIVES: I. To determine the safety, dosimetry, and pharmacokinetics of 64Cu-GRIP B PET in patients with solid tumor malignancy (3 males, 3 females). (Cohort A) II. To determine the mean percent change in both tumor maximum standardized uptake value (SUVmax) and ratio of SUVmax//blood average standardized uptake value (SUVave) on 64Cu-GRIP B PET in patients with participants with metastatic renal cell carcinoma (RCC) and urothelial carcinoma (UC) (Cohort B) or metastatic castration-resistant prostate cancer (mCRPC) (Cohort C). SECONDARY OBJECTIVES: I. To determine the safety and average organ dosimetry of 64Cu-GRIP B PET in patients with participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C) or other solid tumor malignancies (Cohort D). II. To descriptively report the patterns of intra-tumoral uptake of 64Cu-GRIP B on whole body PET, including by site of disease, uptake by tumor type, inter-tumoral and inter-patient heterogeneity, and tumor-to-background signal in patients with participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C), or other solid tumor malignancies (Cohort D). III. To descriptively report PET at grade \>= 2 immune-related adverse event(s) in patients with metastatic RCC and UC (Cohort B) who have 64Cu-GRIP B PET performed within 14 days of onset of event. IV. To descriptively report the number of lesions identified on 64Cu-GRIP B PET compared with conventional imaging in patients with participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C), or other solid tumor malignancies (Cohort D). V. To determine whether baseline uptake on 64Cu-GRIP B PET is associated with subsequent clinical outcomes including objective response, progression-free survival, prostate-specific antigen 50% reduction (PSA50) response, and immune-related adverse events in participants with metastatic RCC and UC (Cohort B), mCRPC (Cohort C), or other solid tumor malignancies (Cohort D). OUTLINE: Patients are assigned to 1 of 4 cohorts: Cohort A: Participants with metastatic GU malignancy (renal,urothelial, or prostate) Cohort B: Participants with metastatic renal cell carcinoma (RCC) or urothelial cancer (UC). Cohort C: Participants with mCRPC Cohort D: Participants with solid tumor malignancies All participants will receive 64Cu-GRIP B PET at baseline. For participants in Cohorts B and C, another PET scan will be performed 8 weeks and at disease progression. Participants in Cohort D will undergo PET/CT or PET/MRI throughout the study and may undergo an optional 64Cu-GRIP B PET at the time of progression. Safety monitoring includes adverse event assessment at screening, 60 minutes (+/- 15 min), 2 hours (+/- 30 min), and 24 hours (+/- 4 hours) following 64Cu-GRIP B injections. Participants will be followed for up to 2 years for longitudinal endpoints.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
DIAGNOSTIC
Masking
NONE
Enrollment
91
Given IV prior to imaging
Imaging procedure
University of California, San Francisco
San Francisco, California, United States
RECRUITINGFrequency 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
Time frame: Up to 8 weeks
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 frame: Up to 8 weeks
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.
Time frame: Up to 8 weeks
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.
Time frame: Up to 8 weeks
Area under the concentration-time curve (AUC) (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 area under the concentration-time curve (AUC) from hour 0 to the last measurable concentration (AUC0-t; min\*unit/mL)
Time frame: Up to 8 weeks
AUC extrapolated to infinity (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 AUC extrapolated to infinity (AUC0-∞; min\*unit/mL)
Time frame: Up to 8 weeks
Median clearance (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 volume of plasma which is completely cleared of a substance per minute (mL/min).
Time frame: Up to 8 weeks
Apparent terminal elimination rate constant (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 apparent terminal elimination rate constant.
Time frame: Up to 8 weeks
Apparent terminal elimination half-life (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 apparent terminal elimination half-life (t1/2; min).
Time frame: Up to 8 weeks
Change in SUVmax (Cohorts B, C, and D)
For Cohorts B, C and D, descriptive statistics will be used to summarize the change in SUVmax from baseline to 8 weeks at lesion level for participants in Cohorts B \& C.
Time frame: Up to 8 weeks
Change in SUVmax/SUVave (Cohorts B, C, and D)
For Cohorts B, C and D, descriptive statistics will be used to summarize the change in the ratio of SUVmax/SUVave from baseline to 8 weeks at lesion level for participants in Cohorts B \& C.
Time frame: Up to 8 weeks
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
Time frame: Up to 8 weeks
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.
Time frame: Up to 2 years
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.
Time frame: Up to 8 weeks
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
Time frame: Up to 2 years
Median change in SUVmax-ave from baseline with reported immune-related adverse event (Cohorts 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 patient-level
Time frame: Up to 2 years
Association of baseline uptake with object response (ORR) (Cohorts B, C and D)
For Cohort B, C and D , to analyze the association between the baseline in SUVmax and with subsequent response by RECIST 1.1 for Cohort B and modified RECIST 1.1/PCWG3 criteria, metastatic lesions will be segregated based on objective response by RECIST 1.1 criteria on follow up conventional imaging.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Time frame: Up to 2 years
Association of baseline uptake with progression-free survival (PFS) (Cohorts B, C and D)
For Cohorts B, C and D, to assess the association between the baseline SUVmax with progression-free survival, defined as the time from date of initiation of checkpoint inhibition to subsequent progression by Prostate Cancer Clinical Trials Working Group 3 (PCWG3)/RECIST criteria, the participant cohort will be dichotomized above and below the median PFS.
Time frame: Up to 2 years
Association of baseline uptake with reported PSA50 response (Cohort C)
For cohort C, to assess the association between the baseline in SUVmax with the patient cohort will be dichotomized into PSA50 vs. non-PSA50 responders.
Time frame: Up to 2 years
Association of baseline uptake with reported immune-related adverse events (irAEs)(Cohorts B, C and D)
For Cohorts B, C and D,to assess the association between the baseline in SUVmax with the patient cohort will be dichotomized into irAE vs. non-irAE reporters.
Time frame: Up to 2 years