The U.S. Food and Drug Administration (FDA) has approved Astellas Pharma Inc.’s VYLOY (zolbetuximab-clzb) in combination with fluoropyrimidine- and platinum-containing chemotherapy for the first-line treatment of adults with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive as determined by an FDA-approved test. VYLOY is the first and only CLDN18.2-targeted therapy approved in the U.S.
 
Moitreyee Chatterjee-Kishore, Ph.D., M.B.A., Senior Vice President and Head of Immuno-Oncology Development, Astellas, said: “The approval of VYLOY as the first and only targeted therapy for CLDN18.2-positive patients in the U.S. further delivers on our relentless pursuit of scientific progress for devastating diseases like gastric and GEJ cancers, which are often only discovered at the advanced stage. This achievement is the result of years of dedicated research and development focused on targeting a novel biomarker, and we are grateful to the patients, investigators, and Astellas team members who have made this important advancement for patients a reality.”
 
Samuel J. Klempner, M.D., Associate Professor, Harvard Medical School, Medical Oncologist at Massachusetts General Hospital, Boston, said: “While there have been advances in the first-line treatment of locally advanced unresectable and metastatic gastric and GEJ cancers in the last several years, there is still a tremendous unmet need among our patients. The approval of VYLOY, based on the pivotal Phase 3 SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive, and for those on the frontlines of treatment decision-making.”
 
The approval is based on results from the Phase 3 SPOTLIGHT and GLOW clinical trials. The SPOTLIGHT study evaluated VYLOY plus mFOLFOX6 (a combination chemotherapy regimen that includes oxaliplatin, leucovorin, and fluorouracil) compared to placebo plus mFOLFOX6. The GLOW study evaluated VYLOY plus CAPOX (a combination chemotherapy regimen that includes capecitabine and oxaliplatin) compared to placebo plus CAPOX.
 
Both trials met their primary endpoint, progression-free survival (PFS), as well as a key secondary endpoint, overall survival (OS), in patients treated with VYLOY plus chemotherapy compared to placebo plus chemotherapy. Across the SPOTLIGHT and GLOW trials, the most common all-grade treatment-emergent adverse events (TEAEs) reported in the VYLOY treatment arms were nausea, vomiting and decreased appetite.
 
An FDA-approved test is used to identify patients who may be eligible for VYLOY. The VENTANA CLDN18 (43-14A) RxDx Assay from Roche is an FDA-approved IHC test used to help determine CLDN18.2 status. Testing is available in the U.S. at multiple reference laboratories nationwide and is expected to expand to additional laboratories over time.
 
Following today’s FDA decision, VYLOY is now approved in five markets worldwide. Astellas has submitted other applications for VYLOY to regulatory agencies worldwide, and they are currently being reviewed.