FDA Approves Astellas' VYLOY™ for Advanced Gastric and GEJ Cancer

Astellas Pharma Inc. has announced the approval of VYLOY™ (zolbetuximab-clzb) by the U.S. Food and Drug Administration (FDA). This approval marks VYLOY as the first CLDN18.2-targeted treatment available in the U.S. for adults suffering from advanced gastric and gastroesophageal junction cancer with CLDN18.2 positive tumors. VYLOY will be administered in combination with chemotherapy containing fluoropyrimidine and platinum for patients who cannot undergo surgery or have metastatic HER2-negative gastric or GEJ adenocarcinoma, as per an FDA-approved test.

Clinical trials, namely SPOTLIGHT and GLOW, have shown that approximately 38% of patients screened were CLDN18.2 positive. The positivity of CLDN18.2 is defined by moderate to strong membranous CLDN18 immunohistochemical staining in 75% or more of tumor cells, established through the VENTANA® CLDN18 (43-14A) RxDx Assay from Roche. Astellas has collaborated with Roche to develop an immunohistochemistry companion diagnostic test to identify patients suitable for VYLOY.

The approval of VYLOY is based on data from the Phase 3 SPOTLIGHT and GLOW clinical trials. In the SPOTLIGHT trial, VYLOY was tested in combination with mFOLFOX6, a chemotherapy regimen including oxaliplatin, leucovorin, and fluorouracil. In the GLOW trial, VYLOY was tested with CAPOX, a chemotherapy regimen with capecitabine and oxaliplatin. Both trials achieved their main goals, showing improvement in progression-free survival (PFS) and overall survival (OS) in patients treated with VYLOY and chemotherapy versus chemotherapy alone. The most common side effects included nausea, vomiting, and decreased appetite.

An FDA-approved test, the VENTANA CLDN18 (43-14A) RxDx Assay from Roche, is necessary to identify patients eligible for VYLOY. This testing is available across various laboratories in the U.S. and will expand further. For more information on where to access this test, visit VYLOYhcp.com.

Following the FDA's decision, VYLOY is now approved in multiple markets worldwide, including Japan, the United Kingdom, the European Union, South Korea, and the U.S. Japan was the first to approve VYLOY in March 2024. The UK Medicines and Healthcare products Regulatory Agency approved it in August, followed by the European Commission in September, and the Ministry of Food and Drug Safety in South Korea. Astellas is also seeking approvals in other countries, with ongoing reviews.

VYLOY (zolbetuximab-clzb) is a claudin 18.2-directed cytolytic antibody approved for first-line treatment in combination with chemotherapy for adults with advanced or metastatic HER2-negative gastric or GEJ adenocarcinoma, provided their tumors test CLDN18.2 positive. As a monoclonal antibody, VYLOY targets and binds to CLDN18.2 protein, depleting CLDN18.2-positive cells through antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).

Patients treated with VYLOY in combination with chemotherapy should be monitored for hypersensitivity reactions and infusion-related reactions. Severe nausea and vomiting are common, especially during the first treatment cycle. Pretreatment with antiemetics is recommended, and further management may involve dose interruption or discontinuation of VYLOY depending on the severity of side effects.

Gastric and gastroesophageal junction cancer is a significant health concern globally, with a high incidence of late-stage diagnosis due to overlapping symptoms with less severe gastrointestinal conditions. Risk factors include older age, male gender, family history, H. pylori infection, smoking, and GERD. The five-year survival rate for metastatic gastric cancer is low, highlighting the need for innovative treatments like VYLOY that target specific biomarkers.

Astellas continues to explore the potential of VYLOY through additional clinical trials and is also developing ASP2138, a bispecific monoclonal antibody targeting CD3 and CLDN18.2. Further research and regulatory reviews will determine the future availability and application of these treatments.