64Cu-GRIP B in Patients With Advanced Malignancies
A First-in-Human, Phase I/II PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients With Advanced Malignancies
4 other identifiers
interventional
91
1 country
1
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1 prostate-cancer
Started May 2023
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 24, 2023
CompletedStudy Start
First participant enrolled
May 25, 2023
CompletedFirst Posted
Study publicly available on registry
June 5, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 31, 2026
ExpectedStudy Completion
Last participant's last visit for all outcomes
January 31, 2027
March 17, 2026
March 1, 2026
3.6 years
May 24, 2023
March 13, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (11)
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
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.
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.
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.
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)
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)
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).
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.
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).
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.
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.
Up to 8 weeks
Secondary Outcomes (9)
Frequency of treatment-emergent adverse events (Cohorts B, C, and D)
Up to 8 weeks
Mean SUVmax in metastatic lesions by disease site (Cohorts B, C and D)
Up to 2 years
Percent of lesions detected for metastatic participants (Cohorts B, C and D)
Up to 8 weeks
Median change in SUVmax from baseline with reported immune-related adverse event (Cohort B)
Up to 2 years
Median change in SUVmax-ave from baseline with reported immune-related adverse event (Cohorts B)
Up to 2 years
- +4 more secondary outcomes
Study Arms (4)
Cohort A: 64Cu-GRIP B, Solid Tumor Malignancy participants
EXPERIMENTALParticipants with solid tumor malignancies (3 males, 3 females), dosimetry calculation will be performed by obtaining whole body (vertex to thighs) PET images up to five time points from 0.5 to 24 hours post 64Cu-GRIP B injections. An additional intravenous line will be placed in the contra-lateral arm to collect blood for this group.
Cohort B: 64Cu-GRIP B, RCC and UC participants
EXPERIMENTALParticipants with renal cell and urothelial carcinoma will have longitudinal imaging performed prior to treatment outside of this study with anti-programmed death-1 (PD-1)/anti-PD-1 ligand 1 (PD-L1) blockade (with or without concomitant anti-CTLA4 treatment), after 8 weeks of checkpoint blockade, and again at the time of disease progression by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Cohort C: 64Cu-GRIP B, mCRPC participants
EXPERIMENTALParticipants with metastatic castration resistant prostate cancer (mCRPC)) will have longitudinal imaging performed prior to treatment outside of this study, 8 weeks following initiation of treatment outside of this study, and at the time of disease progression by Prostate Cancer Working Group 3 (PCWG3) criteria.
Cohort D: 64Cu-GRIP B, Advanced malignancies
EXPERIMENTALparticipants with solid tumor malignancies will have longitudinal imaging performed prior to treatment outside of this study, 8 weeks following initiation of treatment, and the opportunity to have an optional scan at the time of progression.
Interventions
Given IV prior to imaging
Imaging procedure
Eligibility Criteria
You may qualify if:
- 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.
- +7 more criteria
You may not qualify if:
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Rahul Aggarwallead
- National Cancer Institute (NCI)collaborator
- U.S. Army Medical Research Acquisition Activitycollaborator
Study Sites (1)
University of California, San Francisco
San Francisco, California, 94143, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Rahul Aggarwal, MD
University of California, San Francisco
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- DIAGNOSTIC
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
May 24, 2023
First Posted
June 5, 2023
Study Start
May 25, 2023
Primary Completion (Estimated)
December 31, 2026
Study Completion (Estimated)
January 31, 2027
Last Updated
March 17, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share