NCCH2212, An investigator initiated Phase I trial to determine the recommended dose of diagnostic radioactive drug 64Cu-NCAB001 in pancreatic cancer patients without clinically distant metastasis - PRIME-64

Start Date01 Sep 2023

Sponsor / Collaborator-

100 Clinical Results associated with 64Cu-NCAB001

100 Translational Medicine associated with 64Cu-NCAB001

100 Patents (Medical) associated with 64Cu-NCAB001

Literatures (Medical) associated with 64Cu-NCAB001

PharmaceuticsQ3 · MEDICINE

Characterization and Stabilization of a New 64Cu-Labeled Anti-EGFR Antibody NCAB001 for the Early Detection of Pancreatic Cancer with Positron Emission Tomography

Q3 · MEDICINE

ArticleOA

Author: Waki, Atsuo ; Ueno, Makoto ; Naito, Kenichiro ; Yoshida, Sei ; Higashi, Tatsuya ; Yoshii, Yukie ; Ito, Kimiteru ; Tachibana, Tomoko ; Igarashi, Chika ; Matsumoto, Hiroki ; Zhang, Ming-Rong ; Kurihara, Hiroaki ; Hihara, Fukiko

Early diagnosis of pancreatic cancer using current imaging modalities remains challenging. We have developed a new approach to identify tumor lesions ≥ 3 mm in the pancreas by positron emission tomography (PET) with a new intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Generally, in clinical research, a radiometal-antibody complex must be prepared immediately before use at the imaging site. To make 64Cu-NCAB001 ipPET available to daily clinical practices in a sustainable way, the NCAB001-chelator conjugate and 64Cu-NCAB001 must be characterized and stabilized. NCAB001 was manufactured under cGMP conditions. NCAB001 was conjugated with a bifunctional chelator (p-SCN-Bn-PCTA), and the antibody-chelator conjugate (PCTA-NCAB001) was characterized by LC/MS and ELISA. Thereafter, to effectively manufacture 64Cu-NCAB001, we developed a new formulation to stabilize PCTA-NCAB001 and 64Cu-NCAB001. An average of three PCTA chelators were conjugated per molecule of NCAB001. The relative binding potency of PCTA-NCAB001 was comparable to cetuximab. The formulation consisting of acetate buffer, glycine, and polysorbate-80 stabilized PCTA-NCAB001 for a year-long storage. Additionally, this formulation enabled the stabilization of 64Cu-NCAB001 for up to 24 h after radiolabeling with a sufficient radioactivity concentration for clinical use. These results may accelerate the future use of 64Cu-NCAB001 ipPET in clinical settings for the early diagnosis and treatment of pancreatic cancer.

PharmaceuticalsQ3 · MEDICINE

Evaluation of 64Cu-Labeled New Anti-EGFR Antibody NCAB001 with Intraperitoneal Injection for Early PET Diagnosis of Pancreatic Cancer in Orthotopic Tumor-Xenografted Mice and Nonhuman Primates

Q3 · MEDICINE

ArticleOA

Author: Igarashi, Chika ; Zhang, Ming-Rong ; Hatazawa, Jun ; Naito, Kenichiro ; Yamaya, Taiga ; Shimosegawa, Eku ; Yoshii, Yukie ; Ueno, Makoto ; Higashi, Tatsuya ; Hihara, Fukiko ; Waki, Atsuo ; Tachibana, Tomoko ; Kurihara, Hiroaki ; Tashima, Hideaki ; Yoshida, Sei ; Matsumoto, Hiroki ; Ooe, Kazuhiro ; Watabe, Tadashi ; Ito, Kimiteru

Objectives: To improve the prognosis of pancreatic cancer, new imaging methods to identify tumor lesions at a size of <1 cm are urgently needed. To approach this clinical issue, we developed a new method to detect small tumor lesions in the pancreas (≥3 mm) by positron emission tomography (PET) using an intraperitoneally (ip)-administered 64Cu-labeled new anti-epidermal growth factor receptor (EGFR) antibody (encoded as NCAB001), called 64Cu-NCAB001 ipPET. Methods: NCAB001 was manufactured under cGMP conditions and labeled with 64Cu. The radiochemical and biological properties of 64Cu-NCAB001 were evaluated. Tumor uptake of an ip-administered 64Cu-NCAB001 in mice with orthotopic pancreatic tumor xPA1-DC xenografts was also evaluated. Pharmacokinetics and radiation dosimetry were examined using PET images acquired after the ip administration of 64Cu-NCAB001 into cynomolgus monkeys with pharmacologic safety monitoring. Results: Radio-chromatography, cell-binding assays, and biodistribution of 64Cu-NCAB001 in mice were identical to those of our previous data with clinically available cetuximab. Small tumor lesions in the pancreas (≥3 mm) of mice could be identified by 64Cu-NCAB001 ipPET. The ip administration of 64Cu-NCAB001 into monkeys was safely conducted using ultrasound imaging. PET images in monkeys showed that ip-administered 64Cu-NCAB001 was distributed throughout the intraperitoneal cavity for up to 6 h and cleared thereafter. Most of the radioactivity was distributed in the liver and the large intestine. The radioactivity around the pancreas became negligible 24 h after administration. The estimated human effective dose was 0.0174 mSv/MBq. Conclusion: Our data support the initiation of clinical trials of 64Cu-NCAB001 ipPET to transfer this promising tool for the early diagnosis of pancreatic cancers.

Pharmaceutics

Preclinical Safety Evaluation of Intraperitoneally Administered Cu-Conjugated Anti-EGFR Antibody NCAB001 for the Early Diagnosis of Pancreatic Cancer Using PET

Article

Author: Ito, Kimiteru ; Yoshida, Sei ; Ueno, Makoto ; Waki, Atsuo ; Higashi, Tatsuya ; Shinada, Mitsuhiro ; Yoshii, Yukie ; Igarashi, Chika ; Tachibana, Tomoko ; Matsumoto, Hiroki ; Kurihara, Hiroaki ; Naito, Kenichiro ; Hihara, Fukiko

Detecting tumor lesions <1 cm in size using current imaging methods remains a clinical challenge, especially in pancreatic cancer. Previously, we developed a method to identify pancreatic tumor lesions ≥3 mm using positron emission tomography (PET) with an intraperitoneally administered 64Cu-labeled anti-epidermal growth factor receptor (EGFR) antibody (64Cu-NCAB001 ipPET). Here, we conducted an extended single-dose toxicity study of 64Cu-NCAB001 ipPET in mice based on approach 1 of the current ICH M3 [R2] guideline, as our new drug formulation contains 45 μg of the antibody. We used NCAB001 labeled with stable copper isotope instead of 64Cu. The total content of size variants was approximately 6.0% throughout the study. The relative binding potency of Cu-NCAB001 to recombinant human EGFR was comparable to that of cetuximab. The general and neurological toxicities of Cu-NCAB001 ipPET at 62.5 or 625 μg/kg were assessed in mice. The no-observed-adverse-effect level of Cu-NCAB001 was 625 μg/kg, a dose approximately 1000-fold higher at the μg/kg level than the dose of 64Cu-NCAB001 in our formulation (45 µg). The size variants did not affect the safety of the formulation. Therefore, clinical studies on the efficacy of 64Cu-NCAB001 ipPET for early detection of pancreatic cancer using PET imaging can be safely conducted.

100 Deals associated with 64Cu-NCAB001

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Pancreatic Cancer	Preclinical	JP	National Institutes for Quantum & Radiological Science & TechStartup	25 May 2023

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

64Cu-NCAB001

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation