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NCT Number: NCT06916442

Granzyme B-targeted PET Imaging Monitoring Tumor Responses to Immunotherapy

Malignant solid tumors, characterized by their persistently high incidence and mortality rates, pose a significant threat to human health and life, imposing a substantial societal burden. Molecular imaging enables the non-invasive, in vivo visualization of tumorigenesis and progression at the molecular level. Compared to traditional morphology-based imaging techniques, molecular imaging provides more precise information for early tumor diagnosis, treatment efficacy assessment, and clinical disease management. 18F-FDG PET/CT imaging is currently the most widely used molecular imaging modality. However, under immunotherapy, FDG accumulates extensively in activated T cells, leading to increased false-positive evaluations. It fails to effectively distinguish metabolic hyperactivity between proliferative tumor cells (indicative of true progressive disease) and infiltrating immune cells (associated with pseudoprogression), thereby complicating the assessment of immunotherapy efficacy. Therefore, exploring novel molecular imaging probes with high specificity is of critical importance for patients undergoing tumor immunotherapy, as it can lead to more accurate evaluation of treatment efficacy. Granzyme B (GZMB), a serine protease released from cytoplasmic granules of cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells, induces apoptosis in target cells, particularly tumor cells-a central mechanism of tumor immunotherapy. This makes GZMB a promising molecular target for evaluating immunotherapy efficacy. This study aims to assess tumor immunotherapy outcomes using GZMB-targeted PET imaging and compare its performance with 18F-FDG PET/CT. The goal is to achieve timely and accurate efficacy evaluation and longitudinal monitoring, identify potential beneficiaries, optimize clinical decision-making, and ultimately deliver personalized precision treatment to improve overall treatment outcomes.

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Key information

Conditions

PET/CT Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipodystrophy Lipodystrophy, Congenital Generalized Metabolic Diseases Metabolism, Inborn Errors Nutritional and Metabolic Diseases Skin Diseases Skin Diseases, Metabolic Skin and Connective Tissue Diseases Solid Tumors, Adult Solid Tumors, Advanced Solid Tumors

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Observational

Primary location

About this study

This investigator-initiated trial (IIT) aims to investigate the clinical utility of Granzyme B (GZMB)-targeted PET imaging for the early prediction of immunotherapy response in patients with malignant solid tumors. GZMB, a protease secreted by cytotoxic T lymphocytes, serves as a direct indicator of immune-mediated tumor killing activity. The GZMB-targeted tracer has demonstrated high target affinity and favorable pharmacokinetics in preclinical studies, showing potential to overcome the limitations of 18F-FDG PET in distinguishing between pseudoprogression and true progression.

In this prospective, single-arm observational study, patients with histologically confirmed malignant solid tumors (e.g., NSCLC, HNSCC, CRC, etc.) scheduled to receive immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1) will undergo baseline 18F-FDG PET/CT scans. Following 2~3 cycles of immunotherapy, they will undergo both GZMB-targeted PET/CT and 18F-FDG PET/CT scans within one week. PET parameters (SUVmax, SUVmean, tumor-to-background ratio) will be measured, calculated, and then correlated with pathologic response or objective response rate (ORR). The sensitivity, specificity, and accuracy of these parameters in monitoring tumor responses to immunotherapy will be analyzed. The diagnostic performance of both PET modalities will be compared. Additionally, this study will explore the correlations between PET parameters on GZMB-targeted PET imaging and the expression levels of GZMB and CD8+ in tumor tissue.

The study is funded by Zhongnan Hospital of Wuhan University. The results may establish GZMB-targeted PET imaging as a non-invasive tool for identifying patients likely to benefit from immunotherapy, thereby enabling the development of personalized treatment strategies.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Voluntarily participate and sign the written informed consent form.
  • Aged 18 to 90 years (inclusive), regardless of gender.
  • Treatment-naïve patients with pathologically confirmed malignant solid tumors scheduled to receive immunotherapy.
  • Willing and able to adhere to scheduled visits, treatment plans, and laboratory tests.

Exclusion criteria

  • Pregnant or lactating patients.
  • Patients with a known allergy to GZMB-targeted imaging agents or synthetic excipients.
  • Fasting blood glucose level exceeding 11.0 mmol/L prior to 18F-FDG administration.
  • Patients unable to undergo PET/CT imaging (e.g., inability to lie supine, claustrophobia, severe anxiety related to radiation exposure).
  • Patients with poor compliance or other factors deemed by the investigator to preclude participation in the study.

Treatment and study plan

PET/CT Imaging with GZMB-targeted tracer

Diagnostic Test

Intravenous administration of GZMB-targeted tracer (150-200 MBq), followed by whole-body PET/CT scan 30~60 minutes post-injection.

Primary outcomes

  1. The sensitivity and specificity of Granzyme B targeted PET imaging monitoring tumor responses to immunotherapy

    Time frame: 4 years

    We will measure imaging parameters (SUVmax, SUVmean, tumor-to-background ratio), correlating with pathologic response or objective response rate (ORR). The sensitivity, specificity, and accuracy of these two PET/CT imaging modalities for early evaluation of immunotherapy response will be calculated/compared. This study will use pathological findings as the gold standard and clinical follow-up as a reference.

Study contacts

Contact information is provided by the study sponsor or research team.

Yong He, MD, PhD

CONTACT

[email protected]

+86-27-67812698

Sponsors and collaborators

Lead sponsor

Zhongnan Hospital

Other

Registry information

Official study title

A Single-Arm, Open-Label, Exploratory Study of Granzyme B-Targeted PET Imaging for Evaluating Tumor Response to Immunotherapy in Solid Tumors

Acronym: GZMB_PET

Important dates

Study start
2025
Primary completion
2027
Study completion
2027
First posted
Apr 8, 2025
Registry last updated
Apr 8, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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