A Phase 1b, Open Label, Multicenter Study of Positron Emission Tomography With Computed Tomography (PET/CT) Using ⁸⁹Zr Df-IAB22M2C (CD8 PET/CT Tracer) in Patients With Metastatic Melanoma Receiving Bempegaldesleukin (NKTR-214) and Nivolumab
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 3
- 主要终点
- Correlate ⁸⁹Zr Df-IAB22M2C lesion uptake with lesion size and ORR using PET/CT scans
研究概览
简要总结
The main purpose of this study is to investigate the utility of the new investigational imaging agent ⁸⁹Zr Df-IAB22M2C (CD8 PET/CT tracer) to monitor CD8 T-cell expansion and trafficking within tumors and associated tissues in patients with metastatic melanoma undergoing treatment with bempegaldesleukin and nivolumab as a single agent and in combination.
详细描述
NKTR-214 is a cytokine (Investigational Agent), a protein which is found to expand certain immune cells (known as CD8+ T Cells and Natural Killer Cells) to promote their anti-tumor effects. Nivolumab is a full human monoclonal antibody that binds to a molecule called PD-1 (programmed cell death protein 1) on immune cells and promotes anti-tumor effects.
⁸⁹Zr Df-IAB22M2C is an experimental injected molecule containing a radioactive atom; this molecule attaches to CD8+ T cells and allows those T cells to be seen on PET/CT scans.
Part 1: A total of 4 eligible patients will be enrolled into part 1. During Cycle 1, patients will receive single agent NKTR-214, 3 injections ⁸⁹Zr Df-IAB22M2C , and 6 PET/CT scans. Starting with Cycle 2, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study.
Once the PET/CT imaging data from Part 1 have been reviewed, Part 2 will open for enrollment.
Part 2: A total of 20 eligible patient will be enrolled into part 2. During Cycle 1, patients will receive single agent NKTR-214 or nivolumab, 2 injections of ⁸⁹Zr Df-IAB22M2C , and 3 PET/CT scans. In Cycle 2 and beyond, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. During Cycle 2, patients will receive 1 injection of ⁸⁹Zr Df-IAB22M2C and 1 PET/CT scan.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 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
- •Provide written, informed consent to participate in the study and follow the study procedures
- •Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1
- •Measurable disease per RECIST 1.1 criteria
- •Patients must have histologically confirmed metastatic melanoma with measurable, stage IV disease per American Joint Committee on Cancer (AJCC) staging system
- •In patients with a single RECIST measurable lesion, the lesion must be a non-cutaneous lesion.
- •Fresh biopsy
- •Treatment-naive patients (i.e., no prior systemic anticancer therapy for unresectable or metastatic melanoma).
排除标准
- •Patients who have an active, known or suspected autoimmune disease
- •Patients must not have received prior IL-2 therapy
- •Prior treatment with an anti PD-1, anti PD-L1, or anti cytotoxic T lymphocyte associated protein 4 (anti CTLA-4) antibody, agents that target IL-2, or any other antibody or drug specifically targeting T cell co-stimulation or immune checkpoint pathways
- •Need for >2 antihypertensive medications for hypertension management
- •Other protocol-defined inclusion/exclusion criteria apply
研究组 & 干预措施
Part 1 Initial Cohort to Evaluate the Biodistribution of CD8 Cells
During Cycle 1, patients will receive single-agent NKTR-214, 3 injections of 89Zr-Df-IAB22M2C, and 6 PET/CT scans. Starting with Cycle 2, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. Once the PET/CT imaging data from Part 1 have been reviewed, Part 2 will open for enrollment.
干预措施: Bempegaldesleukin (NKTR-214) (Biological)
Part 1 Initial Cohort to Evaluate the Biodistribution of CD8 Cells
During Cycle 1, patients will receive single-agent NKTR-214, 3 injections of 89Zr-Df-IAB22M2C, and 6 PET/CT scans. Starting with Cycle 2, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. Once the PET/CT imaging data from Part 1 have been reviewed, Part 2 will open for enrollment.
干预措施: Nivolumab (Biological)
Part 1 Initial Cohort to Evaluate the Biodistribution of CD8 Cells
During Cycle 1, patients will receive single-agent NKTR-214, 3 injections of 89Zr-Df-IAB22M2C, and 6 PET/CT scans. Starting with Cycle 2, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. Once the PET/CT imaging data from Part 1 have been reviewed, Part 2 will open for enrollment.
干预措施: ⁸⁹Zr-Df-IAB22M2C (Drug)
Part 2 Expansion Cohort to Evaluate the Biodistribution of CD8 Cells
During Cycle 1, patients will receive single-agent NKTR-214 or nivolumab, 2 injections of 89Zr-Df-IAB22M2C, and 3 PET/CT scans. In Cycle 2 and beyond, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. During Cycle 2, patients will receive 1 injection of 89Zr-Df-IAB22M2C and 1 PET/CT scan.
干预措施: Bempegaldesleukin (NKTR-214) (Biological)
Part 2 Expansion Cohort to Evaluate the Biodistribution of CD8 Cells
During Cycle 1, patients will receive single-agent NKTR-214 or nivolumab, 2 injections of 89Zr-Df-IAB22M2C, and 3 PET/CT scans. In Cycle 2 and beyond, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. During Cycle 2, patients will receive 1 injection of 89Zr-Df-IAB22M2C and 1 PET/CT scan.
干预措施: Nivolumab (Biological)
Part 2 Expansion Cohort to Evaluate the Biodistribution of CD8 Cells
During Cycle 1, patients will receive single-agent NKTR-214 or nivolumab, 2 injections of 89Zr-Df-IAB22M2C, and 3 PET/CT scans. In Cycle 2 and beyond, patients will receive NKTR-214 in combination with nivolumab q3w for the remainder of the study. During Cycle 2, patients will receive 1 injection of 89Zr-Df-IAB22M2C and 1 PET/CT scan.
干预措施: ⁸⁹Zr-Df-IAB22M2C (Drug)
结局指标
主要结局
Correlate ⁸⁹Zr Df-IAB22M2C lesion uptake with lesion size and ORR using PET/CT scans
时间窗: Approximately 18 months
Correlation between amount of ⁸⁹Zr Df-IAB22M2C lesion uptake (before and after monotherapy treatment and after combination treatment) with the change in lesion size and the objective response rate (ORR)
Lesion uptake of 89Zr-Df-IAB22M2C (CD8 PET/CT tracer) before and after monotherapy treatment with mechanistically different immunotherapies, bempegaldesleukin (NKTR-214) and nivolumab as well as after combination treatment with NKTR-214 and nivolumab.
时间窗: Approximately 18 months
Lesion uptake of 89Zr-Df-IAB22M2C (CD8 PET/CT tracer) before and after monotherapy treatment with mechanistically different immunotherapies, bempegaldesleukin (NKTR-214) and nivolumab as well as after combination treatment with NKTR-214 and nivolumab.
次要结局
未报告次要终点