A Phase I Trial to Assess Safety, Tolerability, Pharmacokinetics, Radiation Dosimetry, and Positron Emission Tomography (PET) Imaging Properties of 89Zr-labeled hNd2 (NMK89) in Patients With Pancreatic Cancer Histologically Positive for MUC5AC
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 3
- 主要终点
- Safety and tolerability of a single infusion of NMK89: physical examination 2
研究概览
简要总结
This trial will be a non-randomized, Phase I trial to evaluate safety, tolerability, biodistribution, radiation dosimetry, pharmacokinetics and PET imaging properties following an infusion of 37 MBq (1 mCi) of 89Zr-labeled hNd2* (NMK89) in patients with pancreatic cancer that are positive for MUC5AC. Image acquisition is conducted using a PET/CT machine.
* hNd2: Recombinant humanized Nd2 (anti-human MUC5AC monoclonal antibody)
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
- •Willing and able to provide informed consent.
- •Male or female ≥ 18 years of age.
- •Histologically confirmed diagnosis of pancreatic adenocarcinoma.
- •Willing to provide biopsy specimens for purposes of confirmation of MUC5AC expression.
- •Confirmed MUC5AC expression at pre-screening.
- •Measurable disease.
- •Female patients of child-bearing potential must have a negative serum pregnancy test within 30 days prior to infusion of NMK
- •Willing to comply with the study protocol requirements.
- •Willing to provide a tumor resection specimen or biopsy specimen, if the patient undergoes tumor resection or biopsy between Day 16 and Day 60.
排除标准
- •Known hypersensitivity to the investigational medicinal product (IMP) or any of the excipients.
- •History of another primary cancer within the 2 years prior to enrollment, except for the curatively treated in situ cancers.
- •Exposure to any investigational treatments within 30 days prior to the planned date of infusion of NMK
- •Ongoing toxicity ≥ Grade
- •Pleural effusion or peritoneal fluid ≥ Grade
- •Active hepatitis B, hepatitis C, HIV, or other progressing infectious disease.
- •Uncontrolled diabetes.
- •Autoimmune disease or idiopathic thrombocytopenic purpura.
- •Exposure to any radiopharmaceuticals.
- •Planned antineoplastic therapies on the planned date of NMK89 infusion.
- •Use of bevacizumab or any other anti-angiogenic agent.
- •Uncontrolled intercurrent illness.
- •Participants do not have adequate organ and marrow function.
- •Female patients that are pregnant or breast-feeding.
- •Positive urine screen for illegal drugs, or abuse of prescribed drugs at Screening.
- •Participants with contraindications to contrast agent injection used for diagnostic CT.
- •Deemed inappropriate to participate by the investigator.
研究组 & 干预措施
NMK89
Patients will receive a single infusion of NMK89
干预措施: NMK89 (Drug)
结局指标
主要结局
Safety and tolerability of a single infusion of NMK89: physical examination 2
时间窗: Screening
Height
Safety and tolerability of a single infusion of NMK89: physical examination 1
时间窗: Screening to Day 8
Body weight
Safety and tolerability of a single infusion of NMK89: vital sign 2
时间窗: Screening to Day 8
Heart rate
Safety and tolerability of a single infusion of NMK89: vital sign 1
时间窗: Screening to Day 8
Body temperature
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 3
时间窗: Screening to Day 8
QRS interval
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 4
时间窗: Screening to Day 8
QT
Safety and tolerability of a single infusion of NMK89: 12-lead ECG (Electrocardiogram) 1
时间窗: Screening to Day 8
PR interval
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 5
时间窗: Screening to Day 8
Corrected QT
Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - hematology
时间窗: Screening to Day 8
Hematology included hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), white blood cell count (total and differential: leukocytes, neutrophils, eosinophils, basophils, lymphocytes, monocytes), red blood cells, platelets.
Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - serum chemistry
时间窗: Screening to Day 8
Serum chemistry included sodium, potassium, chloride, calcium, glucose, creatinine, urea or BUN, albumin, total bilirubin, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, gamma-glutamyl transferase (GGT), lipase, amylase and total protein.
Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - urinalysis
时间窗: Screening to Day 8
Urinalysis included specific gravity, pH, protein, glucose, blood, leukocytes, ketones, nitrite, albumin, creatinine.
Safety and tolerability of a single infusion of NMK89: vital sign 3
时间窗: Screening to Day 8
Systolic blood pressure (SBP)
Safety and tolerability of a single infusion of NMK89: vital sign 4
时间窗: Screening to Day 8
Diastolic blood pressure (DBP)
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 2
时间窗: Screening to Day 8
RR interval
Safety and tolerability of a single infusion of NMK89: Frequency and severity of abnormal adverse events (AEs) (National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v 5.0))
时间窗: Baseline up to Day 60
Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - clotting factors
时间窗: Screening to Day 8
Clotting factors included prothrombin time (quick), reagent-independent prothrombin ratio (international normalized ratio; INR), activated partial thromboplastin time (aPTT).
Safety and tolerability of a single infusion of NMK89: Frequency and severity of abnormal ECOG PS (Eastern Cooperative Oncology Group Performance Status)
时间窗: Screening to Day 8
次要结局
- Biodistribution: Fractional injected 89Zr radioactivity values (percentage of injected dose(%ID))(Day 1 to Day 8)
- Radiation Dosimetry of NMK89: Normalized radiation absorbed doses and normalized effective dose(Day 1 to Day 8)
- Blood Pharmacokinetics (PK): Concentration of total antibody in blood(Pre-infusion (baseline) to Day 8)
- Biodistribution: Time-integrated activity coefficients (TIACs) (hr)(Day 1 to Day 8)
- Optimization of positron emission tomography (PET) Scan Protocol: Optimal time from injection to start of PET(Day 1 to Day 8)
- Predictive radiation dosimetry of hNd2 labeled with therapeutic radionuclide: Normalized absorbed doses and normalized effective dose(Day 1 to Day 8)
- Blood Pharmacokinetics (PK): Concentration of total radioactive counts in blood(Day 1 to Day 8)
- Blood Pharmacokinetics (PK): Abundance ratio of unmetabolized 89Zr-labeled hNd2(%)(Day 1 to Day 8)
- Biological half-life of the radionuclide (hr)(Day 1 to Day 8)
- Public Safety: Radiation measurement(Day 1)
- Urine Pharmacokinetics (PK): Concentration of total antibody in urine(Pre-infusion (baseline) to Day 8)
- Urine Pharmacokinetics (PK): Radioactivity counts of 89Zr-labeled hNd2 and metabolites components(Day 1 to Day 8)
- Urine Pharmacokinetics (PK): Concentration of total radioactive counts in urine(Day 1 to Day 8)