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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Pancreatic Cancer
• Intervention / Treatment: Drug: NMK89

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • Moffitt Cancer Center
      • Contact: Christine Darbouze; Phone Number: 813-745-7253; Email: christine.darbouze@moffitt.org
      • Principal Investigator: Kenneth Gage, MD
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Recruiting
      • BAMF Health
      • Contact: Clayton McNamara; Phone Number: 616-330-2735; Email: Clayton.McNamara@bamfhealth.com
      • Principal Investigator: Harshad R. Kulkarni, MD
  • Washington
    • Seattle, Washington, United States, 98109
      • Recruiting
      • Fred Hutchinson Cancer Center
      • Principal Investigator: Delphine Chen, MD
      • Contact: Heather White; Phone Number: 206-667-5534; Email: hwhite@fredhutch.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide informed consent.
2. Male or female ≥ 18 years of age.
3. Histologically confirmed diagnosis of pancreatic adenocarcinoma.
4. Willing to provide biopsy specimens for purposes of confirmation of MUC5AC expression.
5. Confirmed MUC5AC expression at pre-screening.
6. Measurable disease.
7. Female patients of child-bearing potential must have a negative serum pregnancy test within 30 days prior to infusion of NMK89.
8. Willing to comply with the study protocol requirements.
9. 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:

1. Known hypersensitivity to the investigational medicinal product (IMP) or any of the excipients.
2. History of another primary cancer within the 2 years prior to enrollment, except for the curatively treated in situ cancers.
3. Exposure to any investigational treatments within 30 days prior to the planned date of infusion of NMK89.
4. Ongoing toxicity ≥ Grade 2.
5. Pleural effusion or peritoneal fluid ≥ Grade 3.
6. Active hepatitis B, hepatitis C, HIV, or other progressing infectious disease.
7. Uncontrolled diabetes.
8. Autoimmune disease or idiopathic thrombocytopenic purpura.
9. Exposure to any radiopharmaceuticals.
10. Planned antineoplastic therapies on the planned date of NMK89 infusion.
11. Use of bevacizumab or any other anti-angiogenic agent.
12. Uncontrolled intercurrent illness.
13. ECOG PS: ≥ 2.
14. Participants do not have adequate organ and marrow function.
15. Female patients that are pregnant or breast-feeding.
16. Positive urine screen for illegal drugs, or abuse of prescribed drugs at Screening.
17. Participants with contraindications to contrast agent injection used for diagnostic CT.
18. Deemed inappropriate to participate by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NMK89; Patients will receive a single infusion of NMK89	Drug: NMK89; Route of administration: intravenous infusion

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Nihon Medi-Physics Co., Ltd.

Publications and helpful links

General Publications

• Nakata N, Kobashi N, Okumura Y, Sato M, Matono M, Otsuki K, Tanaka A, Hayashi A. Radiation dosimetry and efficacy of an 89Zr/225Ac-labeled humanized anti-MUC5AC antibody. Nucl Med Biol. 2022 May-Jun;108-109:33-43. doi: 10.1016/j.nucmedbio.2022.02.003. Epub 2022 Feb 26.

Study record dates

Study Major Dates

• Study Start (Actual): October 31, 2023
• Primary Completion (Estimated): June 27, 2024
• Study Completion (Estimated): October 28, 2024

Study Registration Dates

• First Submitted: October 27, 2023
• First Submitted That Met QC Criteria: November 8, 2023
• First Posted (Actual): November 13, 2023

Study Record Updates

• Last Update Posted (Actual): April 1, 2024
• Last Update Submitted That Met QC Criteria: March 29, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: pancreatic cancer; MUC5AC
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Endocrine System Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms
• Other Study ID Numbers: NMK89P101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No