Solid Tumor, Unspecified, Adult, Lymphoma
Conditions
Keywords
cancer immunotherapy, biomarkers, tumor, positron-emission tomography, Granzymes
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
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.
Interventions
DRUGSingle Arm
\[68Ga\]-NOTA-hGZP is a PET imaging agent.
Sponsors
Massachusetts General Hospital
University of Alabama at Birmingham
Chang Gung Memorial Hospital
Cytosite Biopharma Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
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 4-6 hours post injection or until pembrolizumab injection plus a follow up phone call to assess adverse events 1-3 days after injection.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subjects 18 years of age and older. 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. 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. This includes checkpoint inhibitors that are not approved by the US FDA for the indications in this protocol. 3. Subjects who have received a prior 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with clinically meaningful changes in physical examination findings, vital signs or blood chemistry | 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) |
| Number of participants with changes in ECG | 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 checkpoint inhibitor therapy as determined by region of interest analysis (SUVmean). |
| Number of participants with treatment-related Adverse Events (AEs) | Between time of injection and 3 days post injection | The absolute number of participants with AEs according to CTCAE 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 |
| 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 | Compare granzyme B protein quantification from biopsied tissue to the \[68Ga\]-NOTA-hGZP PET uptake acquired at the same location. |
| Quantification of accumulation of [68Ga]-NOTA-hGZP in tumor foci in participants receiving checkpoint inhibitor therapy. | 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) |
| Evaluate the correlation of [68Ga]-NOTA-hGZP accumulation in tumor foci to 6-month outcome. | 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. |
Countries
Taiwan, United States
Outcome results
None listed