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

Pancreatic Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06129422
• Other study ID #: NMK89P101
• Status: Recruiting
• Phase: Phase 1
• Start date: October 31, 2023
• Est. completion date: October 28, 2024

Study information

• Verified date: March 2024
• Source: Nihon Medi-Physics Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: October 28, 2024
• Est. primary completion date: June 27, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pancreatic Cancer
• Pancreatic Neoplasms

Intervention

Drug:
• NMK89
Route of administration: intravenous infusion

Locations

Country	Name	City	State
United States	BAMF Health	Grand Rapids	Michigan
United States	Fred Hutchinson Cancer Center	Seattle	Washington
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Nihon Medi-Physics Co., Ltd.

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of a single infusion of NMK89: physical examination 1	Body weight	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: physical examination 2	Height	Screening
Primary	Safety and tolerability of a single infusion of NMK89: vital sign 1	Body temperature	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: vital sign 2	Heart rate	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: vital sign 3	Systolic blood pressure (SBP)	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: vital sign 4	Diastolic blood pressure (DBP)	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: 12-lead ECG (Electrocardiogram) 1	PR interval	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: 12-lead ECG 2	RR interval	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: 12-lead ECG 3	QRS interval	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: 12-lead ECG 4	QT	Screening to Day 8
Primary	Safety and tolerability of a single infusion of NMK89: 12-lead ECG 5	Corrected QT	Screening to Day 8
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Biological half-life of the radionuclide (hr)	Biological half-life of the radionuclide (hr) will also be estimated.	Day 1 to Day 8
Secondary	Public Safety: Radiation measurement	Public safety will be assessed by acquiring dosimeter readings of a patient following infusion.	Day 1