Zolbetuximab: First Approval

Zolbetuximab (VYLOY™), a recombinant, chimeric, anti-claudin 18.2 (CLDN18.2) monoclonal antibody (mAb), is being developed by Astellas Pharma Inc. for the treatment of patients with HER2-negative (HER2^-), CLDN18.2-positive (CLDN18.2⁺) advanced gastric or gastroesophageal junction (GEJ) adenocarcinoma and CLDN18.2⁺ advanced pancreatic adenocarcinoma. In March 2024, zolbetuximab was approved in Japan for the treatment of patients with HER2^-, CLDN18.2⁺ unresectable, advanced/recurrent gastric cancer (the gastric cancer indication includes GEJ cancer). Zolbetuximab is also undergoing regulatory review for HER2^-, CLDN18.2⁺ advanced gastric or GEJ adenocarcinoma in the USA, the EU, China, Australia and several other countries. This article summarizes the milestones in the development of zolbetuximab leading to this first approval for the treatment of patients with CLDN18.2⁺ gastrointestinal malignancies.