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

NCT04169321 | Completed Phase 1 FDA Drug

• 1 other identifier: 2019-hGZP-101.12
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 3

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

Conditions

Solid Tumor, Unspecified, Adult; Lymphoma

Keywords

cancer immunotherapy; biomarkers, tumor; positron-emission tomography; Granzymes

Outcome Measures

Primary Outcomes (3)

• Number of participants with clinically meaningful changes in physical examination findings, vital signs or blood chemistry

  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)

  up to 4 to 6 hours post-injection

• Number of participants with changes in ECG

  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 checkpoint inhibitor therapy as determined by region of interest analysis (SUVmean).

  up to 4 to 6 hours post-injection

• Number of participants with treatment-related Adverse Events (AEs)

  The absolute number of participants with AEs according to CTCAE 5.0

  Between time of injection and 3 days post injection

Secondary Outcomes (4)

• Evaluation of the accumulation of [68Ga]-NOTA-hGZP in tumor foci in participants receiving checkpoint inhibitor therapy (absolute number of avid lesions per subject)

  up to one-hour post injection

• Quantification of accumulation of [68Ga]-NOTA-hGZP in tumor foci in participants receiving checkpoint inhibitor therapy.

  up to one-hour post injection

• Evaluate the correlation of [68Ga]-NOTA-hGZP accumulation in tumor foci to 6-month outcome.

  6 months

• Correlate uptake of [68Ga]-NOTA-hGZP tracer and granzyme B expression as assessed on optional excisional biopsy when available (melanoma only).

  up to one-hour post injection

Study Arms (1)

Single Arm

EXPERIMENTAL

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

Interventions

Single Arm DRUG

\[68Ga\]-NOTA-hGZP is a PET imaging agent.

Also known as: [68Ga]-NOTA-hGZP, CSB-111

Single Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects 18 years of age and older.
• 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.
• 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.
• ECOG performance status ≤ 2 (Karnofsky ≥ 60%)
• Life expectancy of greater than 6 months.
• Males and females willing to use adequate contraception prior to study and during study participation.
• If female, not of childbearing potential or negative pregnancy test prior to radiotracer injection.
• Willing and able to understand and sign a written informed consent document.
• Willing and able to undergo all study procedures.
• Cohort 3 only: have archival lesion tissue available within 90 days of enrollment either from biopsy or surgery.

You may not qualify if:

• Participants for whom adverse events due to agents administered more than 4 weeks earlier have not resolved to Grade 1 or less.
• Has not received nor is expected to receive an investigational compound within 90 days prior to \[68Ga\]-NOTA-hGZP PET imaging. This includes checkpoint inhibitors that are not approved by the US FDA for the indications in this protocol.
• Subjects who have received a prior checkpoint inhibitor.
• 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.
• Known brain metastases.
• History of allergic reactions to compounds of similar chemical or biologic composition to \[68Ga\]-NOTA-hGZP or pembrolizumab.
• If female, nursing.
• 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.
• Laboratory values
• Leukocytes \< 3000/mcL
• Absolute neutrophil count \< 1500 mcL
• Platelets \< 100,000 mCL
• Total bilirubin \> 1.5 x ULN
• AST/ALT \> 2.5 x ULN
• Albumin \< 2 g/dL

Sponsors & Collaborators

• Cytosite Biopharma Inc.: lead
• Massachusetts General Hospital: collaborator
• University of Alabama at Birmingham: collaborator
• Chang Gung Memorial Hospital: collaborator

Study Sites (3)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Chang-Gung Memorial Hospital

Taoyuan, Guishan, 333, Taiwan

Location

MeSH Terms

Conditions

Lymphoma; Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Colin G Miller, PhD

  CytoSite Bio Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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 4-6 hours post injection or until pembrolizumab injection plus a follow up phone call to assess adverse events 1-3 days after injection.

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 19, 2019
• Study Start: June 16, 2020
• Primary Completion: March 30, 2025
• Study Completion: June 9, 2025
• Last Updated: August 22, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2); TW (1)