A First-in-class Targeted Therapy for Some Gastrointestinal Cancers
The FDA approved the claudin 18.2-targeted therapy Zolbetuximab-clzb for some gastric and gastroesophageal junction cancers.
The U.S. Food and Drug Administration (FDA) has approved zolbetuximab-clzb (Vyloy) plus a chemotherapy regimen consisting of fluoropyrimidine- and platinum-containing drugs for the first-line treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) cancer whose tumors test positive for claudin 18.2 and negative for human epidermal growth factor receptor 2 (HER2).
The FDA concurrently approved a companion diagnostic test for claudin 18.2 that can be used to determine eligibility for zolbetuximab-clzb.
Zolbetuximab-clzb is an antibody that targets the protein claudin 18.2, which is expressed at junctions between cells in the gastrointestinal tract and other organs. Cancer disrupts the normal architecture of cells and exposes claudin 18.2, leaving it vulnerable to therapeutic targeting. Zolbetuximab-clzb binds to claudin 18.2 and activates the immune system against claudin 18.2-expressing cells. This is the first FDA approval for zolbetuximab-clzb and the first FDA approval for any claudin 18.2-targeting therapy.
The approval was based on results from SPOTLIGHT and GLOW, two randomized, multicenter, double-blind phase III clinical trials. Both trials enrolled patients with advanced unresectable or metastatic gastric or GEJ cancer that tested positive for claudin 18.2 expression.
In SPOTLIGHT, 565 patients were randomly assigned (1:1) to receive the fluoropyrimidine- and platinum-containing chemotherapy regimen mFOLFOX6 with either zolbetuximab-clzb or placebo. Patients in the zolbetuximab-clzb arm were 24.9% less likely to experience disease progression or death and 25% less likely to experience death from any cause than patients in the placebo arm.
In GLOW, 507 patients were randomly assigned (1:1) to receive the fluoropyrimidine- and platinum-containing chemotherapy regimen CAPOX with either zolbetuximab-clzb or placebo. Patients in the zolbetuximab-clzb arm were 31.3% less likely to experience disease progression or death and 22.9% less likely to experience death from any cause than patients in the placebo arm.
The recommended dose of zolbetuximab-clzb is dependent upon body surface area. It is administered as an intravenous infusion of 800 mg/m2 for the first dose and either 600 mg/m2 every three weeks or 400 mg/m2 every two weeks for subsequent doses.
Gastric cancer (also called stomach cancer) and GEJ cancer are both cancers of the digestive tract. Gastric cancer affects the lining of the stomach, and GEJ cancer affects the area where the stomach and esophagus meet. According to federal statistics, it was estimated that 26,890 individuals would be diagnosed with stomach cancer and 10,880 patients would die of the disease in the United States in 2024.
The FDA rendered its decision on October 18, 2024. Please check this FDA web page for the latest information about any accelerated approvals in oncology that may have been subsequently withdrawn and are no longer FDA-approved. In addition, this resource has the most updated information on all therapeutics regulated by the FDA.
