PET/CTGZMB_PETNCT06916442
Granzyme B-targeted PET Imaging Monitoring Tumor Responses to Immunotherapy
An observational study of PET/CT and Solid Tumors, Adult, run by Zhongnan Hospital at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- PET/CT, Solid Tumors, Adult, Solid Tumors, Advanced Solid Tumors
- What is being tested?
- PET/CT Imaging with GZMB-targeted tracer
- Type of treatment
- Injection or infusion
- How many people
- 200 participants
- Where
- 1 siteChina
- Study dates
- 1 Apr 2025to 31 Dec 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Zhongnan Hospital of Wuhan University
Wuhan, Hubei, 430071
Yaqun Jiang, MD, PhD, +86-27-67812698, zn004239@whu.edu.cn
About this study
Official title: A Single-Arm, Open-Label, Exploratory Study of Granzyme B-Targeted PET Imaging for Evaluating Tumor Response to Immunotherapy in Solid Tumors
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.
Read the detailed description
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.
- Being tested
- PET/CT Imaging with GZMB-targeted tracer
- Keywords
- Granzyme B, PET Imaging, Immunotherapy Response, Diagnostic Efficacy
- Medical subject headings
- Lipodystrophy, Congenital Generalized
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PET/CT Imaging with GZMB-targeted tracerDiagnostic test
Intravenous administration of GZMB-targeted tracer (150-200 MBq), followed by whole-body PET/CT scan 30~60 minutes post-injection.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: PET/CT Imaging with GZMB-targeted tracer |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2025
- Study start1 Apr 2025 (estimated)
- Primary completion30 Nov 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for PET/CTStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Zhongnan Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Yong He, MD, PhD, Principal investigator, Zhongnan Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06916442
- Sponsor's protocol ID
- IITXM2024005
- Other IDs
- XKJS202026, IITXM2024005
- Acronym
- GZMB_PET
- Status last verified
- Mar 2025
- First submitted
- 31 Mar 2025
- Last updated
- 8 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 35788116
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Open-Label, Exploratory Study of Granzyme B-Targeted PET Imaging for Evaluating Tumor Response to Immunotherapy in Solid Tumors
- ClinicalTrials.gov ID
- NCT06916442
- Acronym / sponsor ID
- GZMB_PET / IITXM2024005
- Keywords
- Granzyme B, PET Imaging, Immunotherapy Response, Diagnostic Efficacy
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 200 participants (estimated)
- Lead sponsor
- Zhongnan HospitalUniversity, hospital or other
- Study start
- 1 Apr 2025 (estimated)
- Primary completion
- 30 Nov 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 8 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Immunotherapy Recipients with Malignant solid tumors | – | Diagnostic Test: PET/CT Imaging with GZMB-targeted tracerParticipants: 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. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PET/CT Imaging with GZMB-targeted tracerIntravenous administration of GZMB-targeted tracer (150-200 MBq), followed by whole-body PET/CT scan 30~60 minutes post-injection. | Diagnostic test | Immunotherapy Recipients with Malignant solid tumors |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2025.
- Results publication: PubMed 35788116Zhou 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Yong He, MD, PhD principal investigator
Zhongnan Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PET/CT and Solid Tumors, Adult, run by Zhongnan Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 8 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yong He, MD, PhD (+86-27-67812698, heyong@whu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The sensitivity and specificity of Granzyme B targeted PET imaging monitoring tumor responses to immunotherapy (time frame: 4 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06916442, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2025.