NEW YORK – The US Food and Drug Administration on Friday approved Astellas' Vyloy (zolbetuximab-clzb) with chemotherapy as a first-line treatment for patients with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive.
This is the first time the FDA has approved a CLDN18.2-directed drug. The agency concurrently approved Roche's Ventana CLDN18 (43-14A) RxDx Assay as a companion diagnostic for identifying gastric cancer patients whose tumors express CLDN18.2.
The agency approved Vyloy in this setting after reviewing results from two randomized Phase III trials, SPOTLIGHT and GLOW, that compared the activity of the CLDN18.2-directed drug plus chemo versus placebo plus chemo. In both trials, the Vyloy-containing regimen demonstrated improvement in both progression-free and overall survival over chemo alone.
The SPOTLIGHT trial explored Vyloy with the fluoropyrimidine-containing chemo mFOLFOX6 versus mFOLFOX6 chemo alone. The median progression-free survival was 10.6 months in the Vyloy arm and 8.7 months in the chemo-only arm. Median overall survival was 18.2 months on Vyloy-chemo versus 15.5 months on chemo alone.
The GLOW trial explored a different chemo regimen, platinum-containing CAPOX chemotherapy, and showed similar improvements with the addition of the CLDN18.2-targeted drug. Vyloy plus CAPOX chemo was associated with a median progression-free survival of 8.2 months, compared to 6.8 months on CAPOX alone. Median overall survival was 14.4 months and 12.2 months, respectively.
"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," Samuel Klempner, associate professor at Harvard Medical School and investigator for the SPOTLIGHT trial, said in a statement. "The approval of Vyloy, based on the pivotal Phase III 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."
Earlier this year, the FDA initially declined to approve Vyloy due to deficiencies at the third-party manufacturing facility that produces the drug. In May, Astellas resubmitted its biologics license application for Vyloy.
Last month, the European Commission approved Vyloy plus chemo for this same indication. Roche's Ventana companion diagnostic also received CE marking in Europe this month to identify patients for treatment with Vyloy. Earlier this year, the UK's Medicines and Healthcare Products Regulatory Agency also approved Vyloy in this setting, and the drug is also approved in Japan and South Korea.