FDA Approves Zolbetuximab Plus Chemotherapy for Patients With HER2-Negative Gastric/Gastroesophageal Junction Adenocarcinoma With CLDN18.2-Positive Tumors

On October 18th, 2024, the US Food and Drug Administration (FDA) approved first-line zolbetuximab plus fluoropyrimidine and platinum-containing chemotherapy for adult patients with locally advanced, unresectable, or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal cancer junction (G/GEJ) adenocarcinoma who are CLDN18.2-positive. The FDA additionally approved the VENTANA CLDN18 RxDx Assay as a companion diagnostic device to identify patients eligible for this regimen. 

This approval was based on results from the double-blind, multicenter SPOTLIGHT and GLOW trials. In the SPOTLIGHT trial, 565 patients were randomized to receive either zolbetuximab plus modified FOLFOX-6 chemotherapy (fluorouracil, leucovorin, and oxaliplatin) or placebo with modified FOLFOX-6 chemotherapy. In the GLOW trial, 507 patients were randomized to receive either zolbetuximab plus CAPOX chemotherapy (capecitabine and oxaliplatin) or placebo with CAPOX chemotherapy. The primary end point in both trials was progression-free survival (PFS), as assessed via an independent review committee. A key secondary end point was overall survival (OS). 

At analysis in the SPOTLIGHT trial, median PFS was 10.6 months in the zolbetuximab arm and 8.7 months in the placebo arm (hazard ratio [HR] 0.751; 95% confidence interval [CI], 0.598 to 0.942; P = .0066). Median OS was 18.2 months in the zolbetuximab arm and 15.5 months in the placebo arm (HR 0.750; 95% CI, 0.601 to 0.936; P = .0053). At analysis in the GLOW trial, median PFS was 8.2 months in the zolbetuximab arm and 6.8 months in the placebo arm (HR 0.687; 95% CI, 0.544 to 0.866; P = .0007). Median OS was 14.4 months in the zolbetuximab arm and 12.2 months in the placebo arm (HR 0.771; 95% CI, 0.615 to 0.965; P = .0118).

The most common serious adverse reactions, occurring in ≥2% of patients, included vomiting, nausea, neutropenia, febrile neutropenia, diarrhea, intestinal obstruction, pyrexia, pneumonia, respiratory failure, pulmonary embolism, decreased appetite, sepsis, decreased platelet count, and upper gastrointestinal hemorrhage. 

The recommended dose of zolbetuximab with fluoropyrimidine and platinum-containing chemotherapy is 800 mg/m² for the first dose and either 600 mg/m² every 3 weeks or 400 mg/m² every 2 weeks for subsequent doses. 

Source: 

FDA approves zolbetuximab-clzb with chemotherapy for gastric or gastroesophageal junction adenocarcinoma. Accessed on October 18, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zolbetuximab-clzb-chemotherapy-gastric-or-gastroesophageal-junction-adenocarcinoma