Officials with the Food and Drug Administration have approved zolbetuximab-clzb (Vyloy, Astellas Pharma US, Inc.) for the first-line treatment of adults with locally advanced unresectable or metastatic HER2-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin 18.2 (CLDN18.2)-positive, as determined by an FDA-approved test.
On the same day as the Vyloy approval, the FDA also approved the Ventana CLDN18 (43-14A) RxDx Assay (Ventana Medical Systems, Inc./Roche Diagnostics) as a companion diagnostic device to identify patients with gastric or GEJ adenocarcinoma who may be eligible for treatment with zolbetuximab.
The FDA based their approval on data from the SPOTLIGHT (NCT03504397) and GLOW (NCT03653507). clinical trials. Both were double-blind, multicenter trials. SPOTLIGHT enrolled 565 patients with CLDN18.2-positive advanced unresectable or metastatic HER2-negative gastric or GEJ adenocarcinoma and randomly assigned them in a 1:1 fashion to receive either zolbetuximab-clzb with mFOLFOX6 chemotherapy or placebo with mFOLFOX6 chemotherapy.
The researchers noted that median progression-free survival was 10.6 months (95% confidence interval [CI]: 8.9-12.5) in the zolbetuximab-clzb/chemotherapy arm and 8.7 months (95% CI: 8.2-0.3) in the placebo/chemotherapy arm (hazard ratio [HR] 0.751 [95% CI: 0.598-0.942]; 1-sided P=.0066). Median overall survival (OS) was 18.2 months (95% CI: 16.4-22.9) and 15.5 months (95% CI: 13.5-16.5), respectively, (HR 0.750 [95% CI: 0.601-0.936]; 1-sided P=0.0053).
In GLOW, 507 patients were randomly assigned to receive either zolbetuximab-clzb with CAPOX chemotherapy or placebo with CAPOX chemotherapy. Median PFS was 8.2 months (95% CI: 7.5-8.8) in the zolbetuximab-clzb/chemotherapy arm and 6.8 months (95% CI: 6.1-8.1) in the placebo/chemotherapy arm (hazard ratio [HR] 0.687 [95% CI: 0.544, 0.866]; 1-sided P=.0007). Median OS was 14.4 months (95% CI: 12.3, 16.5) and 12.2 months (95% CI: 10.3, 13.7), respectively (HR 0.771 [95% CI: 0.615-0.965]; 1-sided P=.0118).
The most common serious adverse reactions in SPOTLIGHT, according to an FDA statement, “were vomiting, nausea, neutropenia, febrile neutropenia, diarrhea, intestinal obstruction, pyrexia, pneumonia, respiratory failure, pulmonary embolism, decreased appetite, and sepsis. The most common serious adverse reactions in GLOW (≥2%) were vomiting, nausea, decreased appetite, decreased platelet count, upper gastrointestinal hemorrhage, diarrhea, pneumonia, pulmonary embolism, and pyrexia.”
The approvals were announced October 18, 2024.
References
- FDA. FDA approves zolbetuximab-clzb with chemotherapy for gastric or gastroesophageal junction adenocarcinoma. Published October 18, 2024. Accessed October 18, 2024. www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junc tion-adenocarcinoma