Clinical trial NCT06129422: Safety, Tolerability, Pharmacokinetics, Radiation Dosimetry, and PET Imaging Properties of 89Zr-labeled hNd2 (NMK89) in Patients With Pancreatic Cancer
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Pancreatic Cancer
Keywords: pancreatic cancer
MUC5AC
Lead sponsor: Nihon Medi-Physics Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2023-11-13
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Safety and tolerability of a single infusion of NMK89: physical examination 1
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: physical examination 2
timeFrame: Screening
measure: Safety and tolerability of a single infusion of NMK89: vital sign 1
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: vital sign 2
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: vital sign 3
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: vital sign 4
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: 12-lead ECG (Electrocardiogram) 1
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: 12-lead ECG 2
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: 12-lead ECG 3
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: 12-lead ECG 4
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: 12-lead ECG 5
timeFrame: Screening to Day 8
measure: 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))
timeFrame: Baseline up to Day 60
measure: Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - hematology
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - serum chemistry
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - clotting factors
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: Clinical laboratory finding - urinalysis
timeFrame: Screening to Day 8
measure: Safety and tolerability of a single infusion of NMK89: Frequency and severity of abnormal ECOG PS (Eastern Cooperative Oncology Group Performance Status)
timeFrame: Screening to Day 8
Secondary outcomes:
measure: Biodistribution: Fractional injected 89Zr radioactivity values (percentage of injected dose(%ID))
timeFrame: Day 1 to Day 8
measure: Biodistribution: Time-integrated activity coefficients (TIACs) (hr)
timeFrame: Day 1 to Day 8
measure: Radiation Dosimetry of NMK89: Normalized radiation absorbed doses and normalized effective dose
timeFrame: Day 1 to Day 8
measure: Optimization of positron emission tomography (PET) Scan Protocol: Optimal time from injection to start of PET
timeFrame: Day 1 to Day 8
measure: Predictive radiation dosimetry of hNd2 labeled with therapeutic radionuclide: Normalized absorbed doses and normalized effective dose
timeFrame: Day 1 to Day 8
measure: Blood Pharmacokinetics (PK): Concentration of total antibody in blood
timeFrame: Pre-infusion (baseline) to Day 8
measure: Blood Pharmacokinetics (PK): Concentration of total radioactive counts in blood
timeFrame: Day 1 to Day 8
measure: Blood Pharmacokinetics (PK): Abundance ratio of unmetabolized 89Zr-labeled hNd2(%)
timeFrame: Day 1 to Day 8
measure: Urine Pharmacokinetics (PK): Concentration of total antibody in urine
timeFrame: Pre-infusion (baseline) to Day 8
measure: Urine Pharmacokinetics (PK): Concentration of total radioactive counts in urine
timeFrame: Day 1 to Day 8
measure: Urine Pharmacokinetics (PK): Radioactivity counts of 89Zr-labeled hNd2 and metabolites components
timeFrame: Day 1 to Day 8
measure: Biological half-life of the radionuclide (hr)
timeFrame: Day 1 to Day 8
measure: Public Safety: Radiation measurement
timeFrame: Day 1
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Grand Rapids
country: United States
facility: BAMF Health
state: Michigan
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
Study officials:
References:
citation: 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.
citation: Kulkarni HR, Maupin KA, Brennan T, Forsberg J, Rogers D, Olson M, Mancini BR, Chang A, Chandana SR, Kobayashi R. First-in-Human Total-Body PET/CT Imaging Using 89Zr-Labeled MUC5AC Antibody in a Patient with Pancreatic Adenocarcinoma. J Nucl Med. 2024 Nov 1;65(11):1815. doi: 10.2967/jnumed.124.268074. No abstract available.