Zolbetuximab Under Priority Review for HER2-Negative Gastric Cancer


If gastric cancer is localized (has not yet spread), it carries a significantly higher 5-year survival rate of 72-75%. But once the cancer spreads, the rate falls lower: 35% when spread regionally and 6-7% when distant. Identifying, developing, and testing new therapies could improve survival and provide a higher quality-of-life. That is what Astellas Pharma is hoping to do as it develops zolbetuximab.

This investigational monoclonal antibody treatment targets Claudin 18.2 (CLDN18.2), a unique set of proteins expressed on the surface of some cancerous cells. In particular, zolbetuximab could function as a first-in-class therapy for people living with locally advanced unresectable (not surgically removable) or metastatic HER2-negative gastric cancer whose tumors do express these proteins. Zolbetuximab is also in development for individuals with locally advanced unresectable or metastatic HER2-negative gastroesophageal junction carcinoma. The treatment binds to CLDN18.2 and then causes cell apoptosis (death).

In mid-July 2023, XTalks reported that Priority Review and Marketing Authorization applications were accepted in both the European Union and the United States. This means, for the United States at least, that the FDA must now deliver an approval decision within 6 months rather than the standard 10. The decision to grant Priority Review followed a review of data from the Phase 3 SPOTLIGHT and Phase 3 GLOW studies. Approximately 1,072 participants enrolled. Of those enrolled, around 407 had tumors that expressed CLDN18.2. Within the studies, researchers evaluated how effective zolbetuximab was with mFOLFOX6 or CAPOX respectively when compared with placebo.

Findings from both studies highlighted the potential benefits of zolbetuximab inclusion in treatment regimens. The first study found that zolbetuximab with mFOLFOX6 lowered the chance that the cancer would progress, as well as the mortality risk, by 24.9%. In the second study, adding zolbetuximab to CAPOX reduced the risk by 31.3%.

The FDA should announce its decision sometime soon after next year begins.

What is Gastric Cancer?

Also known as: Stomach cancer

An estimated 90-95% of gastric cancer cases are adenocarcinoma; this form begins in the cells that line the stomach. In rarer cases, gastric cancer may consist of lymphoma, stromal tumors, carcinoid tumors, small cell carcinoma, leiomyosarcoma, or small cell carcinoma. If you’re male, older in age, or live in less developed countries, you have a higher risk of developing gastric cancer. H. pylori infection, obesity, gastrointestinal reflux disease, a family history of this cancer, and a poor diet are also linked to gastric cancer.

Sometimes gastric cancer goes undiagnosed or even misdiagnosed in early stages. This is because the symptoms can be, at times, nonspecific or indicative of less serious illnesses. However, symptoms tend to intensify as the cancer progresses. Potential signs you might notice can include:

  • Feeling bloated after eating or full after eating small portions
  • Unintended weight loss
  • Persistent stomach pain, heartburn, and indigestion
  • Severe nausea and/or vomiting
  • Vomiting that produces blood
  • Fatigue
  • Bloody stool
  • Jaundice (yellowing of the skin, eyes, and mucous membranes)
  • Dysphagia (difficulty swallowing)
Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

Follow us