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Granzyme B PET Imaging Drug as a Predictor of Immunotherapy Response to Checkpoint Inhibitors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT04169321
Recruitment Status : Recruiting
First Posted : November 19, 2019
Last Update Posted : June 6, 2022
Massachusetts General Hospital
University of Alabama at Birmingham
Chang Gung Memorial Hospital
Information provided by (Responsible Party):
Cytosite Biopharma Inc.

Brief Summary:
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 combination I-O therapy

Condition or disease Intervention/treatment Phase
Melanoma Non-Small Cell Lung Cancer Drug: Single Arm Phase 1

Detailed Description:
This is a first in human research study (Phase I clinical trial) to test the safety and effectiveness of a new radioactive PET imaging drug and biomarker [68Ga]-NOTA-hGZP. It is a multi-center, open label, non-randomized, two dose study to evaluate the safety of [68Ga]-NOTA-hGZP and the ability to predict the clinical response to checkpoint inhibitor therapy within 2 cycles of treatment.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Multiple center, open label, non-randomized, single dose study, in subjects with cancer undergoing or treatment with a checkpoint inhibitor either as a monotherapy or in combination. subjects. Eligible subjects will receive an injection of [68Ga]-NOTA-hGZP pre checkpoint inhibitor administration and a second dose between 5 and 42 days post initial checkpoint inhibitor administration. Upon dosing each subject will undergo PET scans at 40, 60 and 90 minutes post dosing. The images will be analyzed for the distribution of radioactivity. Subjects will be followed for adverse events for approximately 5-6 hours post injection or until pembrolizumab injection plus a follow up phone call to assess adverse events 1-3 days after injection.
Masking: None (Open Label)
Primary Purpose: Diagnostic
Official Title: First in Human Safety of [68Ga]-NOTA-hGZP- PET Imaging in Subjects Receiving Checkpoint Inhibitor Immunotherapy
Actual Study Start Date : June 16, 2020
Estimated Primary Completion Date : December 30, 2025
Estimated Study Completion Date : February 28, 2026

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Single Arm
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.
Drug: Single Arm
[68Ga]-NOTA-hGZP is a PET imaging agent.
Other Names:
  • [68Ga]-NOTA-hGZP
  • CSB-111

Primary Outcome Measures :
  1. Number of participants with clinically meaningful changes in physical examination findings, vital signs or blood chemistry [ Time Frame: up to 4 to 6 hours post-injection ]

    Clinically significant changes from baseline in physical examination findings

    Clinically significant changes from baseline to follow-up analysis in systolic and diastolic blood pressure (mmHg)

    Clinically significant changes from baseline to follow-up analysis in heart rate (beats per minute)

    Clinically significant changes in respiration rate.

    Clinically significant changes from baseline to follow-up analysis in blood chemistry for:

    1. Leukocytes (/mcL),
    2. Absolute neutrophil count (mcL)
    3. Platelets (/mcL)
    4. Total bilirubin (mg/d)
    5. AST/ALT (unitless)
    6. Albumin (g/dL)
    7. Alkaline phosphatase (IU/L)
    8. eGRF (mL/min/1.73 m2)

  2. Number of participants with changes in ECG [ Time Frame: up to 4 to 6 hours post-injection ]
    Clinically significant changes from baseline to follow-up analysis in ECG change in QT (ms) Quantification of [68Ga]-NOTA-hGZP PET accumulation at tumor site in subjects after treatment with pembrolizumab as determined by region of interest analysis (SUVmean).

  3. Number of participants with treatment-related Adverse Events (AEs) [ Time Frame: Between time of injection and 3 days post injection ]
    The absolute number of participants with AEs according to CTCAE 5.0

Secondary Outcome Measures :
  1. Evaluation of the accumulation of [68Ga]-NOTA-hGZP in tumor foci in pembrolizumab participants (absolute number of avid lesions per subject) [ Time Frame: up to one-hour post injection ]
    Identification by the central reader of the number of avid lesions observed in each subject and the number of subjects with avid lesions seen on the PET images

  2. Quantification of accumulation of [68Ga]-NOTA-hGZP in tumor foci in pembrolizumab participants [ Time Frame: up to one-hour post injection ]
    To be determined by region of interest analysis the mean standardized uptake value (SUVmean) (SUV does not have any units)

  3. Evaluate the correlation of [68Ga]-NOTA-hGZP accumulation in tumor foci to 6-month outcome. [ Time Frame: 6 months ]

    Compare quantified [68Ga]-NOTA-hGZP uptake to participant treatment response in individual lesions as assessed at 6-month clinical follow-up and/or CT assessments.

    The number of lesions that were avid and the lesions that showed a decrease in size compared to those which increased in size.

  4. Correlate uptake of [68Ga]-NOTA-hGZP tracer and granzyme B expression as assessed on optional excisional biopsy when available (melanoma only). [ Time Frame: up to one-hour post injection ]
    Compare granzyme B protein quantification from biopsied tissue to the [68Ga]-NOTA-hGZP PET uptake acquired at the same location.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Subjects 18 years of age and older.
  2. 2. Subjects with proven metastatic cancer that is going to be treated with one or more checkpoint inhibitors under the licensed indications for the cancer type. Checkpoint inhibitors include PD-1, PD-L1, CTLA-4 and LAG-3 inhibitors.
  3. Subjects must have at least one lesion ≥ 15 mm in diameter or with two lesions both ≥ 15mm in diameter, when an optional biopsy is planned. Lesion measurements are taken from a diagnostic quality CT or MR image.
  4. ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
  5. Life expectancy of greater than 6 months.
  6. Males and females willing to use adequate contraception prior to study and during study participation.
  7. If female, not of childbearing potential or negative pregnancy test prior to radiotracer injection.
  8. Willing and able to understand and sign a written informed consent document.
  9. Willing and able to undergo all study procedures.
  10. 10. Cohort 3 only: have archival lesion tissue available within 90 days of enrollment either from biopsy or surgery.

Exclusion Criteria:

  1. Participants for whom adverse events due to agents administered more than 4 weeks earlier have not resolved to Grade 1 or less.
  2. Has not received nor is expected to receive an investigational compound within 90 days prior to [68Ga]-NOTA-hGZP PET imaging.
  3. Subjects who have received a checkpoint inhibitor.
  4. Any acute or chronic inflammatory disease or medical conditions that in the investigator's opinion may interfere with the study procedures or the interpretation of the study results such as infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia.
  5. Known brain metastases.
  6. History of allergic reactions to compounds of similar chemical or biologic composition to [68Ga]-NOTA-hGZP or pembrolizumab.
  7. If female, nursing.
  8. Current treatment with systemic steroids, or immunosuppressive agents. Participants with a condition requiring systemic treatment with either corticosteroids (< 10 mg daily prednisone equivalent) inhaled or topical steroids, and adrenal replacement steroid doses > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
  9. Subjects who have exclusion criteria that would prevent them from receiving a CT scan.
  10. Laboratory values

    1. Leukocytes < 3000/mcL
    2. Absolute neutrophil count < 1500 mcL
    3. Platelets < 100,000 mCL
    4. Total bilirubin > 1.5 x ULN
    5. AST/ALT > 2.5 x ULN
    6. Albumin < 2 g/dL
    7. Alkaline phosphatase > 2.5 ULN
    8. eGRF eGFR < 45 mL/min/1.73 m2

Patients who are stable but have values outside the specified ranges may be included with approval of the study medical monitor.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT04169321

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Contact: Colin G Miller, PhD 2679182806
Contact: Lieselotte Bloss, DVM

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United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Jonathan McConathy, MD PhD         
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Pedram Heidari, MD    617-459-7277      
Principal Investigator: Ryan Sullivan, MD         
Chang-Gung Memorial Hospital Active, not recruiting
Taoyuan City, Guishan, Taiwan, 333
Sponsors and Collaborators
Cytosite Biopharma Inc.
Massachusetts General Hospital
University of Alabama at Birmingham
Chang Gung Memorial Hospital
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Study Director: Colin G Miller, PhD CytoSite Bio Inc.
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Responsible Party: Cytosite Biopharma Inc. Identifier: NCT04169321    
Other Study ID Numbers: 2019-hGZP-101.12
First Posted: November 19, 2019    Key Record Dates
Last Update Posted: June 6, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Cytosite Biopharma Inc.:
cancer immunotherapy
biomarkers, tumor
positron-emission tomography
Additional relevant MeSH terms:
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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases