64Cu-GRIP B in Patients With Advanced Malignancies

Prostate Cancer Clinical Trial

Official title:

A First-in-Human, Phase I/II PET Imaging Study of 64Cu-GRIP B, a Radiotracer Targeting Granzyme B, in Patients With Advanced Malignancies

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05888532
• Other study ID #: 23921
• Secondary ID: NCI-2023-040015R
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 25, 2023
• Est. completion date: January 31, 2027

Study information

• Verified date: December 2023
• Source: University of California, San Francisco
• Contact: Khadija Siddiqua
• Phone: (310) 794-7329
• Email: khadija.siddiqua[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

PRIMARY OBJECTIVES:

I. To determine the safety, dosimetry, and pharmacokinetics of 64Cu-GRIP B PET in patients with metastatic GU malignancy (renal, urothelial, or prostate) (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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 91
• Est. completion date: January 31, 2027
• Est. primary completion date: December 31, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. 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

2. Planned treatment with immune checkpoint inhibitor (Cohorts B and C only)

3. Willing to undergo paired tumor biopsies and has safely accessible bone or soft tissue lesion (Cohorts B and C only)

4. The subject is able and willing to comply with study procedures and provide signed and dated informed consent.

5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.

6. Age 18 years or older at the time of study entry.

7. 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

8. 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:

1. Patients who because of age, general medical or psychiatric condition, or physiologic status cannot give valid informed consent.

2. Any condition that, in the opinion of the Principal Investigator, would impair the patient's ability to comply with study procedures.

3. Is currently pregnant or breastfeeding.

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Kidney Neoplasms
• Metastatic Castration-resistant Prostate Cancer
• Prostate Cancer
• Prostatic Neoplasms
• Renal Cancer
• Solid Tumor, Adult
• Urethral Cancer
• Urethral Neoplasms

Intervention

Drug:
• Copper-64 labeled Granzyme B (64Cu-GRIP B)
Given IV prior to imaging

Procedure:
• Positron Emission Tomography (PET)
Imaging procedure

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California

Sponsors (3)

Lead Sponsor	Collaborator
Rahul Aggarwal	National Cancer Institute (NCI), U.S. Army Medical Research Acquisition Activity

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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 (AUC0-8; min*unit/mL)	Up to 8 weeks
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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	Up to 8 weeks
Secondary	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.	Up to 2 years
Secondary	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.	Up to 8 weeks
Secondary	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	Up to 2 years
Secondary	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	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years
Secondary	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.	Up to 2 years