Safety and efficacy of zolbetuximab plus chemotherapy for CLDN18.2-positive gastric cancer: A single-center retrospective study.

308 Background: The GLOW and SPOTLIGHT trials demonstrated that adding zolbetuximab (ZOL) to chemotherapy significantly improved overall survival (OS) and progression-free survival (PFS) compared with chemotherapy alone in patients with CLDN18.2-positive advanced gastric or gastroesophageal junction (AG/GEJ) adenocarcinoma in the first-line setting. However, real-world data on the safety and efficacy of ZOL plus chemotherapy are limited. Methods: We retrospectively analyzed patients with HER2-negative, CLDN18.2-positive AG/GEJ cancer who received ZOL plus chemotherapy between June 2024 and June 2025 at our institution. Incidences of adverse events (AEs) and efficacy outcomes (objective response rate [ORR], PFS, and OS) were assessed. AEs were evaluated by CTCAE v5.0, and treatment efficacy was assessed by RECIST v1.1. Results: A total of 25 patients were included (median age, 64 years [range, 22–78]; male/female, 48%/52%). Performance status was 0, 1, and 2 in 36%, 48%, and 16%. The primary tumor site was the stomach in 96% and GEJ was in 4%. Disease status was unresectable in 64% and recurrent in 36%. Prior gastrectomy was performed in 24%. Histology was adenocarcinoma in 92% (intestinal/diffuse 39%/61%), and neuroendocrine carcinoma in 8%. Fourteen patients (56%) received ZOL plus FOLFOX, and 11 patients (44%) received ZOL plus non-FOLFOX. Treatment was administered as first-line therapy in 17 patients (68%) and as second-line or later therapy in 8 patients (32%). The most frequent grade 2 treatment-related AEs included anemia (44%), hypoalbuminemia (36%), nausea (16%), and neutropenia (12%). Grade ≥3 treatment-related AEs included hypoalbuminemia (28%), neutropenia (24%), anorexia (20%), and anemia (16%). The incidences of nausea and vomiting during ZOL administration were 48%/42%/18% and 8%/4%/0% in the first, second, and third cycle, respectively. The completion rate of ZOL administration was 96%/100%/100% in the first, second, and third cycle, respectively. Among patients with adenocarcinoma and measurable lesions, the ORR was 42.9% in the first-line setting whereas no objective responses were observed in the ≥ second-line settings. Among 17 patients who received first-line treatment for adenocarcinoma, the median PFS was 7.13 months (95% CI, 3.88–NA), and the median OS was not reached. Conclusions: ZOL plus chemotherapy had manageable AEs in real-world patients and exhibited comparable efficacy to that observed in first-line pivotal trials. The frequency of nausea and vomiting during ZOL administration tended to decrease with more treatment cycles.