Pooled analysis of two trials of zolbetuximab in gastric or gastroesophageal junction adenocarcinoma

Zolbetuximab is an IgG1 monoclonale antibody targeting claudin 18.2. Pooled analysis of two multinational phase 3 trials (SPOTLIGHT and GLOW) evaluated progression-free survival and overall survival with zolbetuximab plus first-line chemotherapy versus placebo plus first-line chemotherapy among patients with HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors were positive for claudin 18.2. A total of 1072 patients were randomized to zolbetuximab plus chemotherapy (n=537) or placebo plus chemotherapy (n=535). In the combined analysis, the median progression-free survival was 9.2 months in the zolbetuximab group and 8.2 months in the placebo group (HR 0.71; 95% CI 0.61-0.83) while the median overall survival was 16.4 months in the zolbetuximab group and 13.7 months in the placebo group (0.77; 0.67-0.89). Types of subsequent anicancer therapies were balanced between the treatment groups. During the treatment period, the most common adverse events were nausea (76.0% of patients in the zolbetuximab group and 56.2% of patients in the placebo group) and vomiting (66.8% and 34.2%, respectively). The authors conclude that zolbetuximab plus chemotherapy resulted in longer progression-free survival and overall survival than placebo plus chemotherapy among patients with HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors were positive for claudin 18.2.