64Cu-GRIP B in Patients With Advanced Malignancies

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Copper-64 labeled Granzyme B (64Cu-GRIP B)
  Given IV prior to imaging
• Процедура Positron Emission Tomography (PET)
  Imaging procedure

Первичные конечные точки

• Frequency of treatment-emergent adverse events (Cohort A) [Срок оценки: Up to 8 weeks]
• Percent of injected activity (Cohort A) [Срок оценки: Up to 8 weeks]
• Time to maximum observed concentration (Tmax) (Cohort A) [Срок оценки: Up to 8 weeks]
• Maximum observed concentration (Cmax) (Cohort A) [Срок оценки: Up to 8 weeks]
• Area under the concentration-time curve (AUC) (Cohort A) [Срок оценки: Up to 8 weeks]
• AUC extrapolated to infinity (Cohort A) [Срок оценки: Up to 8 weeks]
• Median clearance (Cohort A) [Срок оценки: Up to 8 weeks]
• Apparent terminal elimination rate constant (Cohort A) [Срок оценки: Up to 8 weeks]
• Apparent terminal elimination half-life (Cohort A) [Срок оценки: Up to 8 weeks]
• Change in SUVmax (Cohorts B, C, and D) [Срок оценки: Up to 8 weeks]

Вторичные конечные точки (9)

• Frequency of treatment-emergent adverse events (Cohorts B, C, and D) [Срок оценки: Up to 8 weeks]
• Mean SUVmax in metastatic lesions by disease site (Cohorts B, C and D) [Срок оценки: Up to 2 years]
• Percent of lesions detected for metastatic participants (Cohorts B, C and D) [Срок оценки: Up to 8 weeks]
• Median change in SUVmax from baseline with reported immune-related adverse event (Cohort B) [Срок оценки: Up to 2 years]
• Median change in SUVmax-ave from baseline with reported immune-related adverse event (Cohorts B) [Срок оценки: Up to 2 years]
• Association of baseline uptake with object response (ORR) (Cohorts B, C and D) [Срок оценки: Up to 2 years]
• Association of baseline uptake with progression-free survival (PFS) (Cohorts B, C and D) [Срок оценки: Up to 2 years]
• Association of baseline uptake with reported PSA50 response (Cohort C) [Срок оценки: Up to 2 years]
• Association of baseline uptake with reported immune-related adverse events (irAEs)(Cohorts B, C and D) [Срок оценки: Up to 2 years]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Диагностика

Центры проведения

США · 1 центр

• University of California, San Francisco — San Francisco

Идентификаторы

NCT: NCT05888532 · 23921 · NCI-2023-04001 · 5R01CA229354 · 5R01CA258297

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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