Granzyme B-targeted PET Imaging Monitoring Tumor Responses to Immunotherapy

NCT06916442 | Not Yet Recruiting

• 2 other identifiers: IITXM2024005XKJS202026
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

PET/CT; Solid Tumors, Adult; Solid Tumors, Advanced Solid Tumors

Keywords

Granzyme B; PET Imaging; Immunotherapy Response; Diagnostic Efficacy

Outcome Measures

Primary Outcomes (1)

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

  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.

  4 years

Study Arms (1)

Immunotherapy Recipients with Malignant solid tumors

Participants: Adults (≥18 years) with histologically confirmed advanced solid tumors (e.g., NSCLC, HNSCC, et al) scheduled to receive immune checkpoint inhibitors (e.g., anti-PD-1/PD-L1). Interventions: * Baseline: 18F-FDG PET/CT scan prior to immunotherapy initiation. * Post-treatment: Dual PET/CT imaging (GZMB-targeted and 18F-FDG) within one week after 1\~2 cycles of immunotherapy. Objectives: * Compare the diagnostic accuracy of GZMB-targeted PET vs. 18F-FDG PET in distinguishing pseudoprogression (immune-related inflammatory response) from true progression. * Evaluate the ability of GZMB-targeted imaging to predict early immunotherapy response. Design: Single-arm observational study; PET parameters (SUVmax, tumor-to-background ratio, et al) will be correlated with clinical outcomes.

Diagnostic Test: PET/CT Imaging with GZMB-targeted tracer

Interventions

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.

Immunotherapy Recipients with Malignant solid tumors

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Eligible participants must voluntarily enroll and provide written informed consent, be aged 18 to 90 years (inclusive) regardless of gender, and have a pathologically confirmed diagnosis of treatment-naïve malignant solid tumors with planned immunotherapy. Additionally, participants must demonstrate willingness and ability to comply with scheduled clinical visits, adhere to prescribed treatment protocols, and complete required laboratory tests.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Zhongnan Hospital: lead

Study Sites (1)

Zhongnan Hospital of Wuhan University

Wuhan, Hubei, 430071, China

Location

Related Publications (1)

• Zhou H, Wang Y, Xu H, Shen X, Zhang T, Zhou X, Zeng Y, Li K, Zhang L, Zhu H, Yang X, Li N, Yang Z, Liu Z. Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy. J Clin Invest. 2022 Aug 15;132(16):e161065. doi: 10.1172/JCI161065.

  PMID: 35788116 BACKGROUND

MeSH Terms

Conditions

Lipodystrophy, Congenital Generalized

Condition Hierarchy (Ancestors)

Lipid Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lipodystrophy; Skin Diseases, Metabolic; Skin Diseases; Skin and Connective Tissue Diseases; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Yong He, MD, PhD

  Zhongnan Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yong He, MD, PhD

CONTACT

+86-27-67812698; heyong@whu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2025
• First Posted: April 8, 2025
• Study Start: April 1, 2025
• Primary Completion (Estimated): November 30, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 8, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)