Safety, Tolerability, Pharmacokinetics, Radiation Dosimetry, and PET Imaging Properties of 89Zr-labeled hNd2 (NMK89) in Patients With Pancreatic Cancer
- Registration Number
- NCT06129422
- Lead Sponsor
- Nihon Medi-Physics Co., Ltd.
- Brief Summary
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)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 10
- 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 NMK89.
- 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.
- 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 NMK89.
- Ongoing toxicity ≥ Grade 2.
- Pleural effusion or peritoneal fluid ≥ Grade 3.
- 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.
- ECOG PS: ≥ 2.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description NMK89 NMK89 Patients will receive a single infusion of NMK89
- Primary Outcome Measures
Name Time Method Safety and tolerability of a single infusion of NMK89: physical examination 2 Screening Height
Safety and tolerability of a single infusion of NMK89: physical examination 1 Screening to Day 8 Body weight
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 5 Screening to Day 8 Corrected QT
Safety and tolerability of a single infusion of NMK89: vital sign 2 Screening to Day 8 Heart rate
Safety and tolerability of a single infusion of NMK89: vital sign 1 Screening to Day 8 Body temperature
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 3 Screening to Day 8 QRS interval
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 4 Screening to Day 8 QT
Safety and tolerability of a single infusion of NMK89: 12-lead ECG (Electrocardiogram) 1 Screening to Day 8 PR interval
Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - hematology 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 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 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 Screening to Day 8 Systolic blood pressure (SBP)
Safety and tolerability of a single infusion of NMK89: vital sign 4 Screening to Day 8 Diastolic blood pressure (DBP)
Safety and tolerability of a single infusion of NMK89: 12-lead ECG 2 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)) Baseline up to Day 60 Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - clotting factors 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) Screening to Day 8
- Secondary Outcome Measures
Name Time Method Biodistribution: Fractional injected 89Zr radioactivity values (percentage of injected dose(%ID)) Day 1 to Day 8 PET/CT image acquisitions will be obtained to assess biodistribution of NMK89 in normal tissues and tumors in patients.
Radiation Dosimetry of NMK89: Normalized radiation absorbed doses and normalized effective dose Day 1 to Day 8 Whole-body radiation dosimetry of NMK89 in patients will be estimated.
Blood Pharmacokinetics (PK): Concentration of total antibody in blood Pre-infusion (baseline) to Day 8 PK will be evaluated based on concentration of total antibody obtained within defined volumes of blood.
Biodistribution: Time-integrated activity coefficients (TIACs) (hr) Day 1 to Day 8 PET/CT image acquisitions will be obtained to assess biodistribution of NMK89 in normal tissues and tumors in patients.
Optimization of positron emission tomography (PET) Scan Protocol: Optimal time from injection to start of PET Day 1 to Day 8 Optimal time from injection to start of PET acquisition will be determined.
Predictive radiation dosimetry of hNd2 labeled with therapeutic radionuclide: Normalized absorbed doses and normalized effective dose Day 1 to Day 8 Whole-body radiation dosimetry (if hNd2 will be labeled with a therapeutic radionuclide) will be estimated.
Blood Pharmacokinetics (PK): Concentration of total radioactive counts in blood Day 1 to Day 8 PK will be evaluated based on concentration of total radioactive counts obtained within defined volumes of blood.
Blood Pharmacokinetics (PK): Abundance ratio of unmetabolized 89Zr-labeled hNd2(%) Day 1 to Day 8 To calculate this ratio, the count of metabolites and non-metabolic components is obtained
Biological half-life of the radionuclide (hr) Day 1 to Day 8 Biological half-life of the radionuclide (hr) will also be estimated.
Public Safety: Radiation measurement Day 1 Public safety will be assessed by acquiring dosimeter readings of a patient following infusion.
Urine Pharmacokinetics (PK): Concentration of total antibody in urine Pre-infusion (baseline) to Day 8 PK will be evaluated based on concentration of total antibody obtained within defined volumes of urine.
Urine Pharmacokinetics (PK): Radioactivity counts of 89Zr-labeled hNd2 and metabolites components Day 1 to Day 8 Radioactivity counts of 89Zr-labeled hNd2 and metabolites components are measured by magnetic separation, and the abundance ratio of unmetabolized 89Zr-labeled hNd2 (%) will be calculated.
Urine Pharmacokinetics (PK): Concentration of total radioactive counts in urine Day 1 to Day 8 PK will be evaluated based on concentration of total radioactive counts obtained within defined volumes of urine.
Trial Locations
- Locations (3)
Fred Hutchinson Cancer Center
🇺🇸Seattle, Washington, United States
Moffitt Cancer Center
🇺🇸Tampa, Florida, United States
BAMF Health
🇺🇸Grand Rapids, Michigan, United States