Safety, Tolerability, Pharmacokinetics, Radiation Dosimetry, and PET Imaging Properties of 89Zr-labeled hNd2 (NMK89) in Patients With Pancreatic Cancer
Study Details
Study Description
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)
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: NMK89 Patients will receive a single infusion of NMK89 |
Drug: NMK89
Route of administration: intravenous infusion
|
Outcome Measures
Primary Outcome Measures
- 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: physical examination 2 [Screening]
Height
- 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: vital sign 2 [Screening to Day 8]
Heart rate
- 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 (Electrocardiogram) 1 [Screening to Day 8]
PR interval
- 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: 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 5 [Screening to Day 8]
Corrected QT
- 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 [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 - 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: 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: Frequency and severity of abnormal ECOG PS (Eastern Cooperative Oncology Group Performance Status) [Screening to Day 8]
Secondary Outcome Measures
- 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.
- 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.
- 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.
- 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 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.
- 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
- 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): 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.
- 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.
- 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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Willing and able to provide informed consent.
-
Male or female ≥ 18 years of age.
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Histologically confirmed diagnosis of pancreatic adenocarcinoma.
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Willing to provide biopsy specimens for purposes of confirmation of MUC5AC expression.
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Confirmed MUC5AC expression at pre-screening.
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Measurable disease.
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Female patients of child-bearing potential must have a negative serum pregnancy test within 30 days prior to infusion of NMK89.
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Willing to comply with the study protocol requirements.
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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.
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History of another primary cancer within the 2 years prior to enrollment, except for the curatively treated in situ cancers.
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Exposure to any investigational treatments within 30 days prior to the planned date of infusion of NMK89.
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Ongoing toxicity ≥ Grade 2.
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Pleural effusion or peritoneal fluid ≥ Grade 3.
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Active hepatitis B, hepatitis C, HIV, or other progressing infectious disease.
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Uncontrolled diabetes.
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Autoimmune disease or idiopathic thrombocytopenic purpura.
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Exposure to any radiopharmaceuticals.
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Planned antineoplastic therapies on the planned date of NMK89 infusion.
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Use of bevacizumab or any other anti-angiogenic agent.
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Uncontrolled intercurrent illness.
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ECOG PS: ≥ 2.
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Participants do not have adequate organ and marrow function.
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Female patients that are pregnant or breast-feeding.
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Positive urine screen for illegal drugs, or abuse of prescribed drugs at Screening.
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Participants with contraindications to contrast agent injection used for diagnostic CT.
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Deemed inappropriate to participate by the investigator.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | BAMF Health | Grand Rapids | Michigan | United States | 49503 |
Sponsors and Collaborators
- Nihon Medi-Physics Co., Ltd.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NMK89P101