Clinical trial NCT05888532: 64Cu-GRIP B in Patients With Advanced Malignancies
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Prostate Cancer
Renal Cancer
Urethral Cancer
Advanced Solid Tumor
Metastatic Castration-resistant Prostate Cancer
Solid Tumor, Adult
Keywords: Imaging Study
Radiotracer
Granzyme B
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
name: U.S. Army Medical Research Acquisition Activity
First posted: 2023-06-05
Enrollment: 91
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of treatment-emergent adverse events (Cohort A)
timeFrame: Up to 8 weeks
measure: Percent of injected activity (Cohort A)
timeFrame: Up to 8 weeks
measure: Time to maximum observed concentration (Tmax) (Cohort A)
timeFrame: Up to 8 weeks
measure: Maximum observed concentration (Cmax) (Cohort A)
timeFrame: Up to 8 weeks
measure: Area under the concentration-time curve (AUC) (Cohort A)
timeFrame: Up to 8 weeks
measure: AUC extrapolated to infinity (Cohort A)
timeFrame: Up to 8 weeks
measure: Median clearance (Cohort A)
timeFrame: Up to 8 weeks
measure: Apparent terminal elimination rate constant (Cohort A)
timeFrame: Up to 8 weeks
measure: Apparent terminal elimination half-life (Cohort A)
timeFrame: Up to 8 weeks
measure: Change in SUVmax (Cohorts B, C, and D)
timeFrame: Up to 8 weeks
measure: Change in SUVmax/SUVave (Cohorts B, C, and D)
timeFrame: Up to 8 weeks
Secondary outcomes:
measure: Frequency of treatment-emergent adverse events (Cohorts B, C, and D)
timeFrame: Up to 8 weeks
measure: Mean SUVmax in metastatic lesions by disease site (Cohorts B, C and D)
timeFrame: Up to 2 years
measure: Percent of lesions detected for metastatic participants (Cohorts B, C and D)
timeFrame: Up to 8 weeks
measure: Median change in SUVmax from baseline with reported immune-related adverse event (Cohort B)
timeFrame: Up to 2 years
measure: Median change in SUVmax-ave from baseline with reported immune-related adverse event (Cohorts B)
timeFrame: Up to 2 years
measure: Association of baseline uptake with object response (ORR) (Cohorts B, C and D)
timeFrame: Up to 2 years
measure: Association of baseline uptake with progression-free survival (PFS) (Cohorts B, C and D)
timeFrame: Up to 2 years
measure: Association of baseline uptake with reported PSA50 response (Cohort C)
timeFrame: Up to 2 years
measure: Association of baseline uptake with reported immune-related adverse events (irAEs)(Cohorts B, C and D)
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
Study officials:
affiliation: University of California, San Francisco
name: Rahul Aggarwal, MD
role: PRINCIPAL_INVESTIGATOR
References: