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.