Multinational phase 3 trial of zolbetuximab plus CAPOX for CLDN18.2-positive gastric or gastroesophageal junction adenocarcinoma

There is an urgent need for first-line treatment options for HER2-negative locally advanced unresectable or metastatic gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Zolbetuximab is a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2) expressed on G/GEJ adenocarcinoma cells. The multinational phase 3 GLOW trial evaluated zolbetuximab plus CAPOX versus placebo plus CAPOX as first-line treatment for CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic G/GEJ adenocarcinoma. Both progression-free survival and overall survival were significantly better with zolbetuximab-CAPOX compared with placebo-CAPOX. Grade 3 or higher treatment-emergent adverse events were similar with zolbetuximab-CAPOX (72.8% of patients) and placebo-CAPOX (69.9%). The authors conclude that zolbetuximab plus CAPOX represents a potential first-line therapy for patients with CLDN18.2-positive, HER2-negative locally advanced unresectable or metastatic G/GEJ adenocarcinoma.