Zolbetuximab (Vyloy)

Mechanism of action

From the NCI Drug Dictionary: A chimeric immunoglobulin G1 (IgG1) monoclonal antibody directed against the tumor-associated antigen (TAA) Claudin18.2 (CLDN18.2; A2 isoform of claudin-18), with potential immunostimulating and antineoplastic activities. Upon administration, zolbetuximab specifically targets and binds to CLDN18.2 expressed on tumor cells. This may kill CLDN18.2-expressing tumor cells by antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), and inhibit cell proliferation.

Diseases for which it is established

• Gastric cancer
• Gastroesophageal junction adenocarcinoma

History of changes in FDA indication

• 2024-10-18: Approved with fluoropyrimidine- and platinum-containing chemotherapy, for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are CLDN18.2 positive, as determined by an FDA-approved test. (Based on GLOW_gastric & SPOTLIGHT)

Also known as

• Code names: GC-182, IMAB-362
• Generic name: zolbetuximab-clzb
• Brand name: Vyloy