Safety, Tolerability, Pharmacokinetics, Radiation Dosimetry, and PET Imaging Properties of 89Zr-labeled hNd2 (NMK89) in Patients With Pancreatic Cancer

Study Overview
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Brief Summary
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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)

Official Title
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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

Conditions
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Pancreatic Cancer

Intervention / Treatment
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* Drug: NMK89


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NMK89<br>Patients will receive a single infusion of NMK89 | Drug: NMK89<br>* Route of administration: intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of a single infusion of NMK89: physical examination 1 | Body weight | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: physical examination 2 | Height | Screening | 
| Safety and tolerability of a single infusion of NMK89: vital sign 1 | Body temperature | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: vital sign 2 | Heart rate | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: vital sign 3 | Systolic blood pressure (SBP) | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: vital sign 4 | Diastolic blood pressure (DBP) | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG (Electrocardiogram) 1 | PR interval | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 2 | RR interval | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 3 | QRS interval | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 4 | QT | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: 12-lead ECG 5 | Corrected QT | Screening to Day 8 | 
| 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 - hematology | 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. | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - serum chemistry | 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. | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - clotting factors | Clotting factors included prothrombin time (quick), reagent-independent prothrombin ratio (international normalized ratio; INR), activated partial thromboplastin time (aPTT). | Screening to Day 8 | 
| Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - urinalysis | Urinalysis included specific gravity, pH, protein, glucose, blood, leukocytes, ketones, nitrite, albumin, creatinine. | Screening to Day 8 | 
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biodistribution: Fractional injected 89Zr radioactivity values (percentage of injected dose(%ID)) | PET/CT image acquisitions will be obtained to assess biodistribution of NMK89 in normal tissues and tumors in patients. | Day 1 to Day 8 | 
| Biodistribution: Time-integrated activity coefficients (TIACs) (hr) | PET/CT image acquisitions will be obtained to assess biodistribution of NMK89 in normal tissues and tumors in patients. | Day 1 to Day 8 | 
| Radiation Dosimetry of NMK89: Normalized radiation absorbed doses and normalized effective dose | Whole-body radiation dosimetry of NMK89 in patients will be estimated. | Day 1 to Day 8 | 
| Optimization of positron emission tomography (PET) Scan Protocol: Optimal time from injection to start of PET | Optimal time from injection to start of PET acquisition will be determined. | Day 1 to Day 8 | 
| Predictive radiation dosimetry of hNd2 labeled with therapeutic radionuclide: Normalized absorbed doses and normalized effective dose | Whole-body radiation dosimetry (if hNd2 will be labeled with a therapeutic radionuclide) will be estimated. | Day 1 to Day 8 | 
| Blood Pharmacokinetics (PK): Concentration of total antibody in blood | PK will be evaluated based on concentration of total antibody obtained within defined volumes of blood. | Pre-infusion (baseline) to Day 8 | 
| Blood Pharmacokinetics (PK): Concentration of total radioactive counts in blood | PK will be evaluated based on concentration of total radioactive counts obtained within defined volumes of blood. | Day 1 to Day 8 | 
| Blood Pharmacokinetics (PK): Abundance ratio of unmetabolized 89Zr-labeled hNd2(%) | To calculate this ratio, the count of metabolites and non-metabolic components is obtained | Day 1 to Day 8 | 
| Urine Pharmacokinetics (PK): Concentration of total antibody in urine | PK will be evaluated based on concentration of total antibody obtained within defined volumes of urine. | Pre-infusion (baseline) to Day 8 | 
| Urine Pharmacokinetics (PK): Concentration of total radioactive counts in urine | PK will be evaluated based on concentration of total radioactive counts obtained within defined volumes of urine. | Day 1 to Day 8 | 
| Urine Pharmacokinetics (PK): Radioactivity counts of 89Zr-labeled hNd2 and metabolites components | 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. | Day 1 to Day 8 | 
| Biological half-life of the radionuclide (hr) | Biological half-life of the radionuclide (hr) will also be estimated. | Day 1 to Day 8 | 
| Public Safety: Radiation measurement | Public safety will be assessed by acquiring dosimeter readings of a patient following infusion. | Day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pancreatic cancer, MUC5AC