The latest research progress and clinical application news of zolbetuximab

Zolbetuximab (trade name Vyloy) is a drug targeting Claudin-18.2 ( Monoclonal antibodies targeting CLDN18.2 have attracted widespread attention in recent years in the treatment of gastric cancer and gastroesophageal junction adenocarcinoma (G/GEJ cancer). CLDN18.2 is a tight junction protein highly expressed on the surface of gastric cancer cells, with limited expression in normal gastric tissue, making it an ideal tumor target. Zotuximab binds to CLDN18.2 and induces antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), effectively killing tumor cells and bringing new treatment hope to patients with advanced gastric cancer.

Clinical trials are an important support for zotuximab research. At present, the efficacy of zotuximab combined with chemotherapy mainly comes from two key Phase III clinical trials - SPOTLIGHT and GLOW. In the SPOTLIGHT trial, researchers combined zotuximab with the mFOLFOX6 chemotherapy regimen to target CLDN18.2positive and HER2negative advanced gastric cancer and G/GEJ cancer patients. The results showed that the median progression-free survival (PFS) of the treatment group was 10.61 months, which was significantly better than the 8.67 months of the control group; at the same time The median overall survival (OS) also improved to 18.23 months, compared with 15.54 months in the control group, showing clear clinical benefit. In addition, the combination of zotuximab and CAPOX regimen in the GLOW trial also resulted in significant prolongation of PFS and OS, with median PFSmonths. These data not only show that zotuximab effectively improves the survival conditions of patients, but also provide a solid basis for it to become a first-line treatment option.

With the continuous improvement of clinical data, zotuximab has been approved by drug regulatory authorities in many countries. In 2024, the United StatesFDA officially approved zotuximab in combination with standard chemotherapy regimens for the treatment of patients with CLDN18.2 positive advanced gastric cancer and gastroesophageal junction adenocarcinoma, marking a key step in the global cancer treatment field. Immediately afterwards, the European Commission also approved the marketing authorization of the drug in the EU in 2024. China's National Medical Products Administration (NMPA) approved zotuximab for the same indication at the beginning of 2025, which greatly promoted the richness of treatment options for domestic gastric cancer patients. The launch of the drug has brought tangible benefits to the majority of patients, especially for patients with high expression of CLDN18.2. The treatment effect is significantly better than traditional options.

The safety of zotuximab is also of concern. Clinical studies have shown that the most common adverse reactions in combination chemotherapy regimens include nausea, vomiting, loss of appetite, weight loss and gastrointestinal reactions, which are within controllable range. In order to further improve patient tolerance, the research team is exploring adjustments to the dosing regimen, such as trying to omit the loading dose during the first dose, to reduce gastrointestinal toxicity and maintain the same efficacy. Currently, multiple phase II and phase III trials are ongoing, aiming to optimize the use strategy of zotuximab and maximize patient benefits.

In the future, the challenges facing zotuximab will mainly focus on patient selection and price factors. There are individual differences in the expression of CLDN18.2. How to accurately detect and screen patients suitable for using this drug is the key to clinical practice. To this end, scientific researchers have developed a variety of detection methods, including immunohistochemical staining (IHC), to ensure accurate medication. In addition, the higher pricing of zotuximab, especially in emerging markets, may limit the speed of its promotion. Reasonable price adjustment and medical insurance inclusion will become important factors promoting its widespread application.

In addition, future research focuses on the combined application of zotuximab with other immune checkpoint inhibitors or targeted drugs. Combining different drug mechanisms is expected to achieve synergy and further improve patient prognosis. At the same time, related biomarker research and treatment response prediction will also help the development of precision treatment. With the enrichment of clinical data and in-depth research, zotuximab is expected to become one of the core drugs in the treatment of gastric cancer.

In summary, zotuximab is the first targetCLDN18.2The monoclonal antibody, with its clear anti-tumor mechanism and excellent clinical performance, is gradually changing the treatment landscape of advanced gastric cancer. Its approval for marketing not only fills the gap in targeted treatment of gastric cancer, but also brings a double improvement in survival and quality of life for patients. With the release of more data and accumulation of clinical practice, zotuximab is expected to be more widely used in the future and benefit more gastric cancer patients.

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