Safety and efficacy of zolbetuximab plus chemotherapy for claudin 18 isoform 2-positive advanced gastric cancer: initial report of real-world experience.

PURPOSE: This study evaluated the safety and preliminary efficacy of zolbetuximab plus chemotherapy in patients with claudin 18 isoform 2 (CLDN18.2)-positive advanced gastric cancer (AGC).

METHODS

This single-institutional retrospective study enrolled patients with HER2-negative CLDN18.2-positive AGC who were treated with zolbetuximab plus chemotherapy between July 2024 and August 2025.

RESULTS

The cohort included 50 patients with a median age of 63 years (range 30-83; 44% male). The primary tumor location was the stomach in 86% of the patients. Meanwhile, 26% of the patients underwent prior gastrectomy. The PD-L1 combined positive score was < 5 in 87% of patients. Among 24 patients with measurable lesions at baseline, the objective response and disease control rates were 66.7% and 87.5%, respectively. After median follow-up of 7.3 months, median progression-free survival and the duration of response were 6.7 [95% confidence interval (CI) 5.3-10.7] and 6.7 months (95% CI 4.7-10.2), respectively. Grade ≥ 3 treatment-emergent adverse events occurred in 62% of the patients, most commonly hypoalbuminemia (22%), neutrophil count decreased (22%) and anorexia (12%). Subsequent treatment was received by 83% of the patients.

CONCLUSIONS

Zolbetuximab plus chemotherapy was administered to real-world patients with CLDN18.2-positive AGC with acceptable safety profiles and showed preliminary antitumor efficacy. Nevertheless, some adverse events warrant careful monitoring.