Astellas: Vyloy improves survival in patients with advanced gastric cancer

1. Vyloy plus standard-of-care chemotherapy extended overall survival in patients with advanced gastric cancer.

2. The rate of grade 3 or higher adverse events was slightly higher in patients taking Vyloy compared to a placebo group.

The Latest

In the randomized phase 3 SPOTLIGHT and GLOW trials, researchers investigated the efficacy and safety of Vyloy in the treatment of locally advanced, unresectable, or metastatic gastric adenocarcinoma. Patients treated with Vyloy + the standard chemotherapy regimen achieved an overall survival of 18.2 months compared to 15.6 months in the placebo group in the SPOTLIGHT trial, and 14.4 months compared to 12.2 months in the placebo group in the GLOW trial. The rate of grade 3 or higher adverse events was 87% in the Vyloy group versus 78% in the placebo group. Common adverse events included nausea, vomiting, and decreased appetite.

Physician’s Perspective

Gastric adenocarcinoma (a cancer of the stomach) is the fifth most diagnosed cancer worldwide, with incidence rates continuing to rise over the last few decades. Risk factors for gastric cancer include diets rich in nitrates and salts, H. pylori infection, and smoking among others. The current first-line therapy for advanced or metastatic gastric adenocarcinoma is chemotherapy with current survival rates of one year. Although there is immuneotherapy available for treating HER2-positive tumors, there is currently no such option for HER2-negative gastric cancers. Astellas’ Vyloy is a novel immunotherapy that targets a protein on cancer cells (Claudin 18.2), thereby providing a new tool in the treatment of advanced gastric adenocarcinoma.

Molecular Target of Therapy

Vyloy (zolbetuximab) is a monoclonal antibody that targets Claudin-18.2. Claudin 18.2 is a protein that is normally expressed within tight junctions of normal stomach cells. This makes it inaccessible to circulating antibodies. However, during the transformation to cancerous cells, tight junctions break down and allow Claudin-18.2 to become accessible to circulating antibodies. Upon binding to Claudin-18.2, Vyloy mediates antibody-dependent cellular cytotoxicity which means it helps the immune system better recognize and effectively kill the tumor cells.

Company History

Astellas Pharma was established in 2005 through the merger of Yamanouchi Pharmaceutical and Fujisawa Pharmaceutical company. Astellas has been involved in developing therapeutics for metastatic prostate cancer, diabetes, overactive bladder, and neglected tropical infectious diseases. Astellas acquired the right to Vyloy when it purchased Ganymed Pharmaceuticals in 2016. In addition to Vyloy, Astellas currently has several other lines of immune-oncology therapies currently in pre-clinical phase.

Further reading: SPOTLIGHT: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)00620-7/abstract

GLOW: https://www.nature.com/articles/s41591-023-02465-7

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