NCT05888532 · Rahul Aggarwal
64Cu-GRIP B in Patients With Advanced Malignancies
What this study is about
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).
View original scientific description
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.
Interventions
DRUG
Copper-64 labeled Granzyme B (64Cu-GRIP B)
Given IV prior to imaging
PROCEDURE
Positron Emission Tomography (PET)
Imaging procedure
Primary outcome measures
Frequency of treatment-emergent adverse events (Cohort A)
Time frame: Up to 8 weeks
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)
Time frame: Up to 8 weeks
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)
Time frame: Up to 8 weeks
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)
Time frame: Up to 8 weeks
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.
Area under the concentration-time curve (AUC) (Cohort A)
Time frame: Up to 8 weeks
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)
AUC extrapolated to infinity (Cohort A)
Time frame: Up to 8 weeks
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)
Median clearance (Cohort A)
Time frame: Up to 8 weeks
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).
Apparent terminal elimination rate constant (Cohort A)
Time frame: Up to 8 weeks
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.
Apparent terminal elimination half-life (Cohort A)
Time frame: Up to 8 weeks
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).
Change in SUVmax (Cohorts B, C, and D)
Time frame: Up to 8 weeks
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.
Change in SUVmax/SUVave (Cohorts B, C, and D)
Time frame: Up to 8 weeks
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.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Disease characteristics by cohort, as defined by: Cohort A:
- Histologically-confirmed metastatic solid tumor malignancy (3 Male, 3 Female)
- Locally advanced or metastatic disease on conventional imaging Cohort B:
- Histologically-confirmed metastatic renal cell carcinoma (any histologic sub-type) or urothelial carcinoma
- Locally advanced or metastatic disease on conventional imaging Cohort C:
- Histologically-confirmed prostate adenocarcinoma
- Metastatic castration resistant prostate cancer by Prostate Cancer Clinical Trials Working Group 3 (PCWG3) criteria
- Planned treatment with immune checkpoint inhibitor (Cohorts B and C only)
- Willing to undergo paired tumor biopsies and has safely accessible bone or soft tissue lesion (Cohorts B and C only)
- The subject is able and willing to comply with study procedures and provide signed and dated informed consent.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Age 18 years or older at the time of study entry.
- Adequate organ function, as defined by:
- Serum creatinine \<= 1.5 x upper limit of normal (ULN) or estimated creatinine clearance \> 60 mL/min
- Total bilirubin \<= 1.5 x ULN (\< 3 x ULN in patients with documented or suspected Gilbert's).
- Hemoglobin \>= 8.0 g/dL
- Platelet count \>= 75,000/microliter
- Absolute neutrophil count ≥ 1000/microliter
- Patients must not be pregnant or breast feeding. Women of childbearing potential are required to obtain a negative pregnancy test within 14 days of PET Imaging scan. Effective contraception (men and women) must be used in subjects of child-bearing potential.
Exclusion criteria
- 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.
Where
- San Francisco, California
Collaborators
National Cancer Institute (NCI), U.S. Army Medical Research Acquisition Activity
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Mar 17, 2026 · Source of record for eligibility and locations