Granzyme B PET Imaging for Cancer Response Prediction

No longer recruiting at 3 trial locations

Overseen By Colin G Miller, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Cytosite Biopharma Inc.

Must be taking: Checkpoint inhibitors

Must not be taking: Systemic steroids, Immunosuppressive agents

Disqualifiers: Brain metastases, Inflammatory disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 2 cycles of treatment

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new imaging technique to determine if it can predict the effectiveness of a cancer treatment called a checkpoint inhibitor. The trial employs a special PET scan with [68Ga]-NOTA-hGZP to examine cancer in the body. Individuals with metastatic cancer who are about to begin treatment with checkpoint inhibitors might be suitable candidates. Those informed that their cancer has spread and are starting specific immune therapies may find this trial relevant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing an opportunity to be among the first to benefit from this innovative approach.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but you cannot be on systemic steroids or immunosuppressive agents unless they are below certain doses. It's best to discuss your specific medications with the trial team.

What prior data suggests that this PET imaging method is safe for cancer patients?

Research has shown that [68Ga]-NOTA-hGZP PET imaging has been tested for safety and radiation dose measurement in healthy individuals. These studies found the imaging to be well-tolerated, with no major safety concerns, supporting its use in further trials. Researchers are exploring this imaging method to assess the effectiveness of cancer treatments, and it has shown promise in early tests. Although this method is new in human studies, the initial findings are reassuring regarding safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about [68Ga]-NOTA-hGZP because it offers a new way to predict how well cancer treatments might work by using Granzyme B PET imaging. Unlike other methods that only assess cancer size changes, this approach focuses on the biological activity within the tumor. It uses a special tracer that highlights active immune responses against cancer cells, potentially allowing doctors to see treatment effectiveness much earlier. This could lead to quicker, more personalized treatment decisions, offering a significant advantage over current imaging techniques.

What evidence suggests that this imaging technique is effective for predicting cancer treatment response?

Research has shown that a special type of scan, called [68Ga]-NOTA-hGZP PET imaging, can help predict how well cancer patients will respond to immunotherapy. This trial will evaluate the use of [68Ga]-NOTA-hGZP PET imaging in all participants. The scan has shown promise in detecting early responses in stomach cancer patients receiving combined immunotherapy. Studies have also demonstrated its safety and potential effectiveness for patients with skin cancer (melanoma) and a type of lung cancer. The scan uses a special tracer that targets Granzyme B, a protein involved in the immune response, to assess how well the immune system is fighting the cancer. Overall, this could be a helpful tool for making treatment decisions in cancer care. ^{1 2 6 7 8}

Who Is on the Research Team?

Colin G Miller, PhD

Principal Investigator

CytoSite Bio Inc.

Are You a Good Fit for This Trial?

Adults with metastatic cancer eligible for checkpoint inhibitor therapy (PD-1, PD-L1, CTLA-4, LAG-3 inhibitors) can join. They must have a life expectancy over 6 months, at least one sizable tumor lesion, and be able to consent. Excluded are those with unresolved prior treatment side effects, brain metastases, allergies to trial drugs or similar compounds, current steroid/immunosuppressant use (with exceptions), recent investigational drug use or previous checkpoint inhibitors.

Inclusion Criteria

eGRF eGFR < 45 mL/min/1.73 m2

I am not able to become pregnant or have a negative pregnancy test.

My metastatic cancer will be treated with specific immune therapy drugs.

Exclusion Criteria

I am allergic to certain drugs similar to [68Ga]-NOTA-hGZP or pembrolizumab.

I am on low-dose steroids but do not have an active autoimmune disease.

I haven't taken any experimental drugs or treatments in the last 90 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a mass dose of 40 μg or less of [68Ga]-NOTA-hGZP and undergo PET and CT scans to evaluate the safety and predict the clinical response to checkpoint inhibitor therapy

2 cycles of treatment

1 visit (in-person) for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in physical examination findings, vital signs, blood chemistry, and ECG

up to 6 months

Extension

Evaluate the correlation of [68Ga]-NOTA-hGZP accumulation in tumor foci to 6-month outcome and assess treatment response in individual lesions

6 months

What Are the Treatments Tested in This Trial?

Interventions

• [68Ga]-NOTA-hGZP

Trial Overview The trial is testing the safety of a new PET imaging drug [68Ga]-NOTA-hGZP in humans. It aims to see if this drug can predict how well patients respond to immunotherapy using checkpoint inhibitors. This is a single-arm study where all participants receive the same intervention.

How Is the Trial Designed?

Group I: Single Arm Experimental Treatment 1 Intervention

All participants will receive a mass dose of 40 μg or less of \[68Ga\]-NOTA-hGZP (radioactivity dose of 3 mCi to 8 mCi) and have a PET and CT scan.

Who Is Running the Clinical Trial?

Cytosite Biopharma Inc.

Lead Sponsor

Trials

2

Recruited

40+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

University of Alabama at Birmingham

Collaborator

Trials

1,677

Recruited

2,458,000+

Chang Gung Memorial Hospital

Collaborator

Trials

1,117

Recruited

490,000+

Published Research Related to This Trial

Granzyme B PET imaging using the targeted peptide GZP is a highly sensitive and specific method for early assessment of response to cancer immunotherapy, showing 93% sensitivity and 94% negative predictive value in predicting treatment outcomes.

The study demonstrated that GZP PET imaging can effectively compare the efficacy of different checkpoint inhibitor regimens, revealing that sequential dosing of PD-1 and CTLA-4 therapies is as effective as concurrent administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effectiveness of Checkpoint Inhibitor Combinations and Administration Timing Can Be Measured by Granzyme B PET Imaging. Larimer, BM., Bloch, E., Nesti, S., et al.[2020]

A new imaging technology, using a specially engineered peptide called GRIP B, allows researchers to measure the activity of granzyme B (GZMB) in living organisms, providing insights into its biological functions in real-time.

In mouse cancer models, this method successfully detected GZMB activity in tumors and lymphoid tissues, indicating its potential role in immune responses, especially when combined with immune checkpoint inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vivo Measurement of Granzyme Proteolysis from Activated Immune Cells with PET. Zhao, N., Bardine, C., Lourenço, AL., et al.[2023]

The study developed novel SPECT imaging probes, [111 In]IDT and [111 In]IDAT, which effectively target granzyme B, a promising biomarker for enhancing immune checkpoint inhibitor treatments.

In experiments with tumor-bearing mice, these probes demonstrated moderate accumulation in tumors, correlating with granzyme B expression, suggesting their potential utility in monitoring treatment response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and evaluation of 111 In-labeled tetrapeptide-based compounds as single-photon emission computed tomography imaging probes targeting granzyme B. Kazuta, N., Watanabe, H., Ono, M.[2023]

Granzyme B has been identified as a promising early biomarker for predicting responses to cancer immunotherapy, with preclinical studies showing that PET imaging can effectively distinguish between tumor responders and nonresponders in mice.

In human melanoma patients undergoing checkpoint inhibitor therapy, significant differences in granzyme B expression were found between responders and nonresponders, indicating its potential for clinical application as a predictive biomarker.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Granzyme B PET Imaging as a Predictive Biomarker of Immunotherapy Response. Larimer, BM., Wehrenberg-Klee, E., Dubois, F., et al.[2021]

The PET imaging technique using the granzyme B-targeted radiotracer 68Ga-grazytracer can effectively predict tumor responses to immunotherapy, showing better sensitivity in distinguishing responders from nonresponders compared to traditional methods.

In a preliminary clinical trial with 5 patients, 68Ga-grazytracer was safe with no adverse events reported, and its PET results correlated well with clinical responses to immunotherapy, suggesting its potential for improving patient stratification and early response assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive interrogation of CD8+ T cell effector function for monitoring early tumor responses to immunotherapy. Zhou, H., Wang, Y., Xu, H., et al.[2022]

Citations

1. jnm.snmjournals.org jnm.snmjournals.org/content/66/supplement_1/252239

Assessment of Safety and Dosimetry of [68Ga]CSB-111 This study demonstrates the safety and favorable dosimetry profile of [ 68 Ga]CSB-111 in healthy volunteers, supporting its use in larger trials.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05285696

NOTA-hGZP (CSB-111) PET Imaging in Healthy Human ... A Phase 1 Study to Evaluate the Safety and Dosimetry of [68Ga]-NOTA-hGZP (CSB-111) PET Imaging in Healthy Human Volunteers. Conditions.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39389628/

Granzyme B PET/CT Imaging Evaluates Early Response to ... Our results indicated that [ 68 Ga]Ga-NOTA-GSI PET/CT is a promising tool for predicting early response to combined immunotherapy in gastric cancer patients.

4. synapse.patsnap.com synapse.patsnap.com/drug/c7bd8242ce4346c9889c2be6df6cc017

Gallium-68 NOTA hGZP - Drug Targets, Indications, Patents These data come from a Phase I trial assessing the safety and feasibility of GzmB PET imaging in subjects with melanoma and non-small cell lung cancer (NSCLC) ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06982053

[68Ga]Ga-GZP PET for Early Response Prediction in ... This diagnostic study investigates the value of 68Ga-NOTA-GZP PET imaging in predicting and evaluating immunotherapy response in malignant tumors by ...

6. jitc.bmj.com jitc.bmj.com/content/jitc/10/8/e004949.full.pdf

Molecular imaging to support cancer immunotherapy 78 There is one ongoing clinical trial evaluating granzyme PET with [68Ga]Ga- NOTA- hGZP in patients with melanoma and NSCLC treated with pembrolizumab ( ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40441892/

Granzyme B PET Imaging Predicts Response to ... The 68Ga-NOTA-GZP PET signal was increased in tumors responsive to immunotherapy on day 7 and was highly sensitive in predicting response via ...

8. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2020-11400

Granzyme B PET Imaging Drug as a Predictor of ... First in Human Safety of [68Ga]-NOTA-hGZP PET Imaging in subjects with cancer undergoing treatment with a checkpoint inhibitor either as a monotherapy of in ...