First in Human Safety of [68Ga]-NOTA-hGZP- PET Imaging in Subjects Receiving Checkpoint Inhibitor Immunotherapy
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 3
- 主要终点
- Number of participants with clinically meaningful changes in physical examination findings, vital signs or blood chemistry
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
- •Subjects who have exclusion criteria that would prevent them from receiving a CT scan.
- •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
- •Alkaline phosphatase > 2.5 ULN
- •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.
研究组 & 干预措施
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.
干预措施: Single Arm (Drug)
结局指标
主要结局
Number of participants with clinically meaningful changes in physical examination findings, vital signs or blood chemistry
时间窗: 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
时间窗: 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)
时间窗: Between time of injection and 3 days post injection
The absolute number of participants with AEs according to CTCAE 5.0
次要结局
- 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)