Real-world experience with zolbetuximab in CLDN18.2-positive advanced gastric cancer

In this video, Dr Filip Van Herpe discusses Japanese real-world data on zolbetuximab plus chemotherapy in patients with CLDN18.2-positive advanced gastric or gastro-oesophageal junction cancer, presented at ESMO GI 2026.¹ Zolbetuximab is a CLDN18.2-directed monoclonal antibody. Zolbetuximab plus chemotherapy demonstrated progression-free and overall survival benefit compared to placebo plus chemotherapy in the phase III SPOTLIGHT and GLOW trials. This retrospective single-centre analysis evaluated whether the efficacy and safety observed in those studies are also reflected in routine clinical practice. 

The study included 50 patients with HER2-negative, CLDN18.2-positive unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma who received zolbetuximab plus chemotherapy between July 2024 and August 2025. Most patients were treated in the first-line setting (90%). Median progression-free survival was 6.7 months and median overall survival was 18.8 months, broadly consistent with the outcomes reported in the pivotal phase III trials. Among patients with measurable disease, the objective response rate was 66.7% and the disease control rate was 87.5%. 

Dr Van Herpe highlights that the safety profile was also in line with previous experience. Nausea and vomiting remain important adverse events with zolbetuximab, but the Japanese experience suggests that proactive antiemetic management can improve tolerability. He also notes that hypoalbuminaemia was frequently observed, which may be associated with localised oedema and is clinically relevant because this is not typically seen with many other systemic anticancer treatments.

Overall, these real-world data support the feasibility of zolbetuximab plus chemotherapy in CLDN18.2-positive advanced gastric cancer, provided that adverse events are anticipated and actively managed. Dr Van Herpe notes that zolbetuximab is not yet available in routine practice in Belgium, although a second-line study is currently open for patient recruitment. Experience from Japan may therefore help inform clinical practice once CLDN18.2-directed treatment becomes more broadly accessible.