Zolbetuximab plus mFOLFOX6 for locally advanced unresectable or metastatic CLDN18.2-positive, HER2-negative G/GEJ adenocarcinoma

Zolbetuximab is a monoclonal antibody targeting claudin-18 isoform 2 (CLDN18.2). The multinational phase 3 SPOTLIGHT trial compared first-line zolbetuximab plus mFOLFOX6 versus placebo plus mFOLFOX6 for CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastro-esophageal junction (G/GEJ) adenocarcinoma. Both progression-free survival (HR 0.75; p=0.0066) andoverall survival (HR 0.75; p=0.0053) were significantly improved with addition of zolbetuximab to mFOLFOX6. Grade 3 or worse TRAEs were seen in 87% of patients with zolbetuximab plus mFOLFOX and 78% of patients with placebo plus mFOLFOX. The authors conclude that zolbetuximab plus mFOLFOX might represent a new first-line treatment for these patients.