Is zotuximab an immune drug or a targeted drug?

Zolbetuximab (zolbetuximab-clzb)-VYLOY is a targeted drug rather than an immunotherapy drug in the traditional sense. It is a monoclonal antibody that mainly targets a protein called CLDN18.2 (claudin 18.2), which is a tight junction protein that is rarely expressed in normal gastric mucosa but is highly expressed on the surface of cancer cells such as gastric cancer and gastroesophageal junction cancer. Therefore, zotuximab is specifically designed to recognize and bindCLDN18.2, enabling precise attack on tumor cells.

As a form of targeted therapy, zotuximab activates antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) mechanisms by binding to CLDN18.2, helping the body eliminate cancer cells that express this protein. This mechanism is different from immune checkpoint inhibitors, such as PD-1/PD-L1 inhibitors, which mainly indirectly enhance the killing power of T cells by "unlocking" the immune system's recognition of tumors. Zotuximab's mode of action is more direct, focusing on the immune killing process triggered by target expression and antibody binding.

Zotuximab is often used in combination with chemotherapy drugs, such as fluoropyrimidines and platinums, and this combination has shown better efficacy in advanced or metastatic gastric cancer. Its approval was based on data from two key clinical trials of SPOTLIGHT and GLOW, which significantly improved progression-free survival (PFS) and overall survival (OS), and is especially suitable for patients with CLDN18.2-positive, HER2-negative advanced gastric cancer.

Therefore, zotuximab is positioned as a "targeted therapy drug". It has the targeting properties of antibody drugs. Its immunomodulatory effect relies on the antibody-mediated killing pathway rather than directly regulating the function of T cells or immune checkpoints. This is different from mainstream immunotherapy drugs.

Reference materials:https://www.astellas.com/en/news/29401