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

First in Human Safety of [68Ga]-NOTA-hGZP- PET Imaging in Subjects Receiving Checkpoint Inhibitor Immunotherapy

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

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.

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 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.