Astellas Receives Chinese Clinical Approval for Zolbetuximab in First-Line Treatment of CLDN18.2-Positive Metastatic Pancreatic Cancer

On February 10, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that zolbetuximab injection, submitted by Astellas, had received an implied clinical trial approval in China for first-line treatment of patients with metastatic pancreatic cancer. Public information shows that zolbetuximab is an antibody drug targeting Claudin 18.2 (CLDN18.2), which Astellas acquired through a $1.4 billion company acquisition in 2016 and is currently in Phase 3 clinical research globally.

Screenshot source: CDE official website

Claudins are tight junction molecules. To date, researchers have identified many members of the Claudin protein family, among which Claudin 18 has two isoforms: Claudin 18.1 and Claudin 18.2. Studies have found that under normal physiological conditions, Claudin 18.2 is only expressed in differentiated epithelial cells of the gastric mucosa and shows no expression in other healthy tissues. However, Claudin 18.2 exhibits high expression in various tumors such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, and colon cancer. Therefore, Claudin 18.2 may serve as a potential effective target for immunotherapy in solid tumors like gastric cancer and pancreatic cancer.

Although Claudin 18.2 has potential in the field of targeted therapy development for solid tumors, research progress in this area has been relatively slow. It wasn’t until 2016, when Ganymed Pharmaceuticals presented the clinical trial results of its Claudin 18.2 chimeric antibody zolbetuximab at the American Society of Clinical Oncology (ASCO) Annual Meeting, that this anti-cancer molecular target began to attract broader attention in the industry. Astellas immediately acquired Ganymed that year for $1.4 billion, gaining rights to zolbetuximab (formerly known as IMAB362). Public information indicates that zolbetuximab is also one of the first Claudin 18.2-targeting therapies to enter Phase 3 clinical trials globally.

In China, zolbetuximab was approved for clinical use for the first time in 2018, indicated for locally advanced unresectable or metastatic, Claudin18.2-positive and HER2-negative adult gastric and gastroesophageal junction (GEJ) adenocarcinoma. The indication approved for this clinical study is: in combination with nab-paclitaxel and gemcitabine, for the first-line treatment of Claudin18.2-positive metastatic pancreatic cancer patients.

ClinicalTrials.gov shows that multiple clinical trials of zolbetuximab are currently underway. Among them is a global multicenter (including China) Phase 3 clinical trial for the indication of gastric and gastroesophageal junction adenocarcinoma, as well as a Phase 2 clinical study evaluating the efficacy and safety of zolbetuximab in combination with nab-paclitaxel and gemcitabine as a first-line treatment for Claudin18.2-positive metastatic pancreatic adenocarcinoma patients.

We hope that the subsequent clinical research of zolbetuximab will proceed smoothly, bringing new treatment options to patients as soon as possible.

References:

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Feb 10, 2022. From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c

[2]ClinicalTrials.gov website. From https://clinicaltrials.gov/ct2/results?cond=&term=zolbetuximab&cntry=&state=&city=&dist=

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