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)

开始日期2023-10-31

申办/合作机构

Nihon Medi-Physics Co., Ltd.

100 项与抗muc5ac RDC(住友制药) 相关的临床结果

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项与抗muc5ac RDC(住友制药) 相关的文献（医药）

2022-05-01·Nuclear medicine and biology4区 · 医学

Radiation dosimetry and efficacy of an 89Zr/225Ac-labeled humanized anti-MUC5AC antibody

4区 · 医学

Article

作者: Tanaka, Akihiro ; Kobashi, Nobuya ; Matono, Mitsuhiro ; Sato, Mikiko ; Nakata, Norihito ; Okumura, Yuki ; Otsuki, Kumiko ; Hayashi, Akio

INTRODUCTION:

Theranostic applications are currently difficult to achieve owing to the limited evaluation of suitable chelators for therapeutic nuclides, such as ²²⁵Ac and ²²⁷Th. With a focus on targeted α therapy and theranostics using human IgG as a drug-delivery system (i.e., combining highly cytotoxic α-particle emitter radiation with efficient tumor targeting), we developed a recombinant humanized Nd2 (hNd2) as an anti-MUC5AC antibody since MUC5AC is highly expressed in patients with pancreatic cancer. Therefore, we aimed to evaluate the performance of ⁸⁹Zr- (for diagnosis) and ²²⁵Ac- (for therapy) labeling of these antibodies using well-controlled radioisotope (RI)-labeling technology in pancreatic cancer mouse models.

METHODS:

⁸⁹Zr-labeled hNd2 (NMK89) and ²²⁵Ac-labeled hNd2 (NMT25) were manufactured by chemical conjugation using affinity peptides. A binding assay and the evaluation of plasma stability were performed in vitro to confirm the properties of NMK89 and NMT25. In vivo, we evaluated biodistribution, positron emission tomography (PET)/computed tomography (CT) imaging, antitumor effects, and toxicity. Moreover, the exposure dose in humans was estimated based on the biodistribution evaluation in normal mice.

RESULTS:

NMK89 and NMT25 showed binding specificity to MUC5AC and stability with radiochemical purity ≥90% in mice and human plasma following incubation for 168 h. NMK89 showed high accumulation in tumors and low non-specific accumulation in normal tissues. The antitumor effect of NMT25 was dose-dependent and significantly suppressed tumor growth in the NMT25 treatment groups compared with the control group (p < 0.05). NMK89 and NMT25 showed similar pharmacokinetics and biodistribution characteristics. Additionally, the human estimated exposure dose of NMK89 and NMT25 was confirmed, and the effective dose of NMK89 and NMT25 was 0.33 mSv/MBq and 177.5 mSv/MBq, respectively.

CONCLUSION:

NMK89 showed specific accumulation in the MUC5AC-expressing tumors, while NMT25 showed strong antitumor effects. These results suggest NMK89 and NMT25 as promising theranostic agents for pancreatic cancer.

项与抗muc5ac RDC(住友制药) 相关的新闻（医药）

2022-10-25

·PRNewswire

FDA Accepts NMP's Clinical Trial Application for Development of NMK89 as Imaging Agent for Cancer Diagnosis

- Clinical Study Set to Begin, Focusing on Diagnostic Use of Theranostics - TOKYO, Oct. 25, 2022 /PRNewswire/ -- Nihon Medi-Physics Co., Ltd. (NMP), a leading radiopharmaceutical company in Japan, is pleased to announce that the U.S. Food and Drug Administration (FDA) has recently accepted NMP's Investigational New Drug (IND) application to initiate a first-in-human phase I clinical study of "NMK89 (development code)," which is an imaging agent currently developed for cancer diagnostic use in cancer theranostics (a fusion of therapeutics and diagnostics) (*1). The clinical study can now be started. NMK89 is an RI (*2)-labeled humanized anti-MUC5AC (*3) antibody to which zirconium-89, a diagnostic radionuclide, is labeled and has been investigated in non-clinical studies conducted by NMP and Sumitomo Pharma Co., Ltd. as an imaging agent for the diagnosis of MUC5AC-expressing cancer. It has been reported that MUC5AC is highly expressed in pancreatic cancer, liver cancer, colon cancer, gastric cancer, and lung cancer, among others. Non-clinical studies have confirmed that NMK89 accumulates in tumors transplanted with cell lines expressing MUC5AC. NMP is developing NMK89 in one of the research projects (*4) adopted by the Japan Agency for Medical Research and Development (AMED) to enable early commercialization of theranostics for use in nuclear medicine. NMP is conducting the phase I study of NMK89 in the U.S. NMP will promptly begin clinical studies of therapeutic drugs by leveraging the data on NMK89, obtained from the phase I study, to swiftly materialize it as long-awaited theranostics. Notes: (*1) It is a therapeutic concept in which RI-imaging diagnostics is used in advance to determine whether the drug reaches the target protein in the patient and to provide treatment with the radionuclide modified for therapeutic use. This enables therapies that are more closely aligned with a diagnosis and is expected to contribute to personalized medicine and the effective utilization of medical costs. (*2) Radioisotopes - Radiation they emit is used for cancer treatment and diagnosis. (*3) Mucin subtype 5AC - A type of mucin which is the main component of mucus secreted by animal epithelial cells. It is generally expressed in normal tissues of the stomach and trachea but is also reported to be highly expressed in pancreatic cancer and several other cancers. (*4) The research project known as "Development of Antibody Labeling Therapies (with Alpha-Particle) and Companion Diagnostics, in Parallel with Maintenance of Drug Research Facilities to Embody the Concept of Theranostics" was adopted by AMED's "Cyclic Innovation for Clinical Empowerment (CiCLE)" - FY2017 (2nd Conference). About Nihon Medi-Physics Co., Ltd. Nihon Medi-Physics is engaging in ensuring stable supply and research and development of new products as a leading manufacturer of radiopharmaceuticals in Japan. Based on the technological proficiency and trust built over the years, the company is also working on research and development of "theranostics (a combination of therapeutics and diagnostics)," which is a novel medical technology to provide optimal medical service to each patient, as well as on the dissemination of nuclear medicine in Asian countries by licensing its products. The company will continue contributing to society by creating values as a life science company. Official website: SOURCE Nihon Medi-Physics Co., Ltd.

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