First-line zolbetuximab plus CAPOX for advanced CLDN18.2+/HER2- gastric or gastroesophageal junction adenocarcinoma

There is an unmet need for novel targeted therapies that improve outcomes for patients with HER2-negative locally advanced unresectable or metastatic (LA/M) gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Zolbetuximab is a claudine18.2 (CLDN18.2) targeted monoclonal antibody. The multinational phase 3 GLOW trial evaluated first-line zolbetuximab plus CAPOX versus placebo plus CAPOX for LA/M CLDN18.2-positive, HER2-negative LA/M G/GEJ adenocarcinoma. Both PFS and OS were significantly prolonged with zolbetuximab plus CAPOX versus placebo plus CAPOX. Serious grade 3-5 treatment-emergent adverse events were similar in both arms. The authors conclude that these results establish zolbetuximab plus chemotherapy as a potential new standard-of-care option for these patients.