NMK89 PET Imaging for Pancreatic Cancer

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Nihon Medi-Physics Co., Ltd.

Must not be taking: Anti-angiogenics, Radiopharmaceuticals

Disqualifiers: Other cancer, Uncontrolled diabetes, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

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)

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain treatments like bevacizumab or other anti-angiogenic agents. You also cannot have planned antineoplastic therapies on the day of the NMK89 infusion.

What data supports the effectiveness of the treatment NMK89 for pancreatic cancer?

Research shows that using a similar PET imaging agent, 89Zr-5B1, with a preloading technique improved imaging of pancreatic cancer in mice, suggesting that NMK89 might also enhance imaging for better detection and monitoring of the disease. ^{1 2 3 4 5}

Is NMK89 safe for use in humans?

Research on similar 89Zr-labeled compounds, like 89Zr-Df-IAB22M2C and 89Zr-pertuzumab, has shown them to be safe in human studies, with no significant adverse effects reported. ^{3 6 7 8 9}

How is the drug NMK89 different from other treatments for pancreatic cancer?

NMK89 is unique because it uses a radioactive tracer, zirconium-89 (89Zr), to help visualize and track the drug's distribution in the body through PET imaging, allowing doctors to see how well the drug targets pancreatic cancer cells. This approach is different from traditional treatments as it provides real-time, non-invasive insights into the drug's effectiveness and tumor targeting. ^{3 6 10 11 12}

Eligibility Criteria

This trial is for adults with pancreatic cancer that tests positive for MUC5AC. They must be willing to follow the study rules and provide tumor samples if needed. Pregnant women, those with severe fluid buildup, active infections like hepatitis or HIV, recent cancers (except certain treated ones), ongoing drug trials participation, significant organ damage, or uncontrolled illnesses can't join.

Inclusion Criteria

My diagnosis is pancreatic cancer confirmed by tissue analysis.

I am willing to give a sample of my tumor if I have surgery or a biopsy between Day 16 and Day 60.

Willing and able to provide informed consent

Exclusion Criteria

You cannot have the contrast dye used for CT scans due to health reasons.

I have severe fluid buildup in my chest or abdomen.

I do not have active hepatitis B, C, HIV, or any progressing infectious disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive a single infusion of 89Zr-labeled hNd2 (NMK89) and undergo PET/CT imaging

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety, tolerability, and pharmacokinetics from Day 1 to Day 8

1 week

Multiple visits (in-person and virtual)

Treatment Details

Interventions

• NMK89

Trial Overview The trial studies NMK89's safety and how it moves through and affects the body when given as an infusion to pancreatic cancer patients. It involves PET/CT imaging to track the drug's distribution and effects on tumors expressing MUC5AC.

Participant Groups

Group I: NMK89 Experimental Treatment 1 Intervention

Patients will receive a single infusion of NMK89

NMK89 is already approved in United States, Japan for the following indications:

Approved in United States as NMK89 for:

• Pancreatic cancer

Approved in Japan as NMK89 for:

• Pancreatic cancer

Who Is Running the Clinical Trial?

Nihon Medi-Physics Co., Ltd.

Lead Sponsor

Trials

4

Recruited

140+

Findings from Research

In a study of 122 patients with resected pancreatic adenocarcinomas, CA 19-9 levels demonstrated high sensitivity (94%) and accuracy (95%) for detecting cancer recurrence, making it a reliable biomarker for monitoring patients post-surgery.

Combining CA 19-9 testing with imaging techniques like MDCT or FDG-PET-CT resulted in 100% accuracy in detecting pancreatic cancer recurrence, suggesting that this combination could enhance diagnostic effectiveness in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accuracy of multi-detector computed tomography, fluorodeoxyglucose positron emission tomography-CT, and CA 19-9 levels in detecting recurrent pancreatic adenocarcinoma. Hamidian Jahromi, A., Sangster, G., Zibari, G., et al.[2018]

In a study of 67 patients with borderline pancreatic head cancer, a PET protocol identified two types of cancer based on glucose uptake, with significant differences in tumor characteristics and survival outcomes.

Patients with the U-RC type of pancreatic cancer had a longer disease-free survival time (25.3 months) compared to those with the S-RC type (11.2 months), suggesting that PET imaging can help predict cancer recurrence and inform treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigation of Association Between Borderline Pancreatic Head Cancer and Glucose Uptake by Using Positron-Emission Tomographic Studies. Zhang, Y., Qin, L., Zhang, C.[2019]

The PET imaging agent 89Zr-anti-γH2AX-TAT effectively monitors DNA damage in pancreatic cancer in response to chemotherapy, showing higher accumulation in treated tumors compared to untreated ones, indicating its potential for assessing treatment efficacy early on.

In contrast, the standard PET radiotracer 18F-FDG was not effective in indicating therapeutic response, highlighting the superior capability of 89Zr-anti-γH2AX-TAT for evaluating treatment effectiveness in late-stage pancreatic ductal adenocarcinoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-anti-γH2AX-TAT but not 18F-FDG Allows Early Monitoring of Response to Chemotherapy in a Mouse Model of Pancreatic Ductal Adenocarcinoma. Knight, JC., Mosley, MJ., Bravo, LC., et al.[2022]

The study demonstrated that [(18)F]HX4 PET scans are feasible and repeatable in patients with esophageal (EC) and pancreatic (PC) cancer, with good consistency in measuring tumor hypoxia.

The maximum tumor to background ratio (TBRmax) and tumor hypoxic volume (HV) showed reliable repeatability, indicating that [(18)F]HX4 PET could be a valuable tool for planning radiation therapy and monitoring treatment responses in these cancer types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and repeatability of PET with the hypoxia tracer [(18)F]HX4 in oesophageal and pancreatic cancer. Klaassen, R., Bennink, RJ., van Tienhoven, G., et al.[2018]

Preloading with the unmodified anti-CA19.9 antibody 5B1 significantly enhances the imaging contrast and tumor-to-tissue ratios of the PET tracer 89Zr-5B1 in murine models of pancreatic cancer, indicating improved targeting of tumors.

This optimized approach allows for clearer delineation of tumors in both subcutaneous and orthotopic pancreatic cancer models, suggesting that preloading could be a valuable strategy in clinical imaging applications for pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preloading with Unlabeled CA19.9 Targeted Human Monoclonal Antibody Leads to Improved PET Imaging with 89Zr-5B1. Houghton, JL., Abdel-Atti, D., Scholz, WW., et al.[2018]

The study developed a zirconium-89 (89Zr) labeled anti-mesothelin antibody (89Zr-AMA) to track its distribution in pancreatic tumors, showing that it specifically targets mesothelin-expressing tumors with higher uptake than a nonspecific control antibody.

MicroPET imaging demonstrated that 89Zr-AMA provides non-invasive, real-time insights into tumor targeting and biodistribution, which could help optimize the use of antibody-drug conjugates in treating pancreatic cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging the distribution of an antibody-drug conjugate constituent targeting mesothelin with ⁸⁹Zr and IRDye 800CW in mice bearing human pancreatic tumor xenografts. ter Weele, EJ., Terwisscha van Scheltinga, AG., Kosterink, JG., et al.[2021]

The 89Zr-labeled anti-PD-L1 PET imaging technique effectively targets and monitors PD-L1 expression in tumors, showing high specificity and favorable imaging properties in living subjects.

Gemcitabine treatment significantly increased PD-L1 expression in cancer cells, leading to enhanced uptake of the 89Zr-anti-PD-L1, suggesting this method could be useful for tracking chemotherapy effects on tumor PD-L1 levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

89Zr-Labeled Anti-PD-L1 Antibody PET Monitors Gemcitabine Therapy-Induced Modulation of Tumor PD-L1 Expression. Jung, KH., Park, JW., Lee, JH., et al.[2022]

The study demonstrated that CD8 PET imaging using the radiolabeled minibody 89Zr-Df-IAB22M2C is a safe method for visualizing the distribution of CD8+ leukocytes in patients with metastatic solid tumors, with no significant adverse events reported in 15 subjects.

This imaging technique showed potential for predicting early responses to immunotherapy, as increased uptake of the radiotracer in tumors correlated with treatment response in patients undergoing immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody. Farwell, MD., Gamache, RF., Babazada, H., et al.[2022]

This first-in-human study involving 6 patients with HER2-positive metastatic breast cancer demonstrated that 89Zr-pertuzumab PET/CT is safe, with no reported toxicities during the trial.

The imaging technique effectively visualized HER2-positive metastases, confirming its potential for assessing HER2 status in lesions that are difficult to biopsy, and it accurately identified HER2-positive brain metastases in one patient, which was later confirmed by surgical resection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer. Ulaner, GA., Lyashchenko, SK., Riedl, C., et al.[2019]

Immuno-PET using (89)Zr-labeled cmAb U36 demonstrated a sensitivity of 72% for detecting lymph node metastases in head and neck squamous cell carcinoma patients, outperforming conventional imaging methods like CT/MRI in certain aspects.

The accuracy of immuno-PET was 93% for detecting operated lymph node levels, indicating its potential as a reliable diagnostic tool for guiding treatment decisions in patients at high risk for metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. Börjesson, PK., Jauw, YW., Boellaard, R., et al.[2015]

In a study involving 6 patients with HER3-positive tumors, PET imaging showed that the radiolabeled antibody GSK2849330 effectively targeted tumors, confirming its potential for treating these cancers.

The study established dose-dependent effects, with an exploratory ID50 of 2 mg/kg and ID90 of 18 mg/kg, indicating that higher doses of the unlabeled antibody reduced tumor uptake of the radiolabeled version, which helps in optimizing dosing for future treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immuno-PET Imaging to Assess Target Engagement: Experience from 89Zr-Anti-HER3 mAb (GSK2849330) in Patients with Solid Tumors. Menke-van der Houven van Oordt, CW., McGeoch, A., Bergstrom, M., et al.[2020]

The RGD-NGR heterodimer tracer showed superior performance in detecting pancreatic ductal adenocarcinoma (PDAC) compared to its monomeric counterparts and the standard imaging agent [18F]F-FDG, indicating its potential for early detection of this lethal cancer.

In mouse models, the RGD-NGR tracer effectively identified both pre-malignant and malignant pancreatic lesions, suggesting it could be a valuable tool for screening high-risk populations for PDAC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Heterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer. Sun, L., Gai, Y., Li, Z., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Accuracy of multi-detector computed tomography, fluorodeoxyglucose positron emission tomography-CT, and CA 19-9 levels in detecting recurrent pancreatic adenocarcinoma. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Investigation of Association Between Borderline Pancreatic Head Cancer and Glucose Uptake by Using Positron-Emission Tomographic Studies. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

89Zr-anti-γH2AX-TAT but not 18F-FDG Allows Early Monitoring of Response to Chemotherapy in a Mouse Model of Pancreatic Ductal Adenocarcinoma. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Feasibility and repeatability of PET with the hypoxia tracer [(18)F]HX4 in oesophageal and pancreatic cancer. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Preloading with Unlabeled CA19.9 Targeted Human Monoclonal Antibody Leads to Improved PET Imaging with 89Zr-5B1. [2018]

6. United States pubmed.ncbi.nlm.nih.gov

Imaging the distribution of an antibody-drug conjugate constituent targeting mesothelin with ⁸⁹Zr and IRDye 800CW in mice bearing human pancreatic tumor xenografts. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

89Zr-Labeled Anti-PD-L1 Antibody PET Monitors Gemcitabine Therapy-Induced Modulation of Tumor PD-L1 Expression. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

CD8-Targeted PET Imaging of Tumor-Infiltrating T Cells in Patients with Cancer: A Phase I First-in-Humans Study of 89Zr-Df-IAB22M2C, a Radiolabeled Anti-CD8 Minibody. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

First-in-Human Human Epidermal Growth Factor Receptor 2-Targeted Imaging Using 89Zr-Pertuzumab PET/CT: Dosimetry and Clinical Application in Patients with Breast Cancer. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Performance of immuno-positron emission tomography with zirconium-89-labeled chimeric monoclonal antibody U36 in the detection of lymph node metastases in head and neck cancer patients. [2015]

11. United States pubmed.ncbi.nlm.nih.gov

Immuno-PET Imaging to Assess Target Engagement: Experience from 89Zr-Anti-HER3 mAb (GSK2849330) in Patients with Solid Tumors. [2020]

12. United States pubmed.ncbi.nlm.nih.gov

Heterodimeric RGD-NGR PET Tracer for the Early Detection of Pancreatic Cancer. [2023]