2557 Background: Claudin18.2 (CLDN18.2) has emerged as a new target for the treatment of gastric cancer in the first-line (1L) setting with the approval of zolbetuximab. This long-term analysis reports the extended efficacy and safety of satri-cel (autologous CLDN18.2-specific CAR T cells) as sequential therapy after 1L treatment in patients with advanced gastric/gastroesophageal junction (G/GEJ) cancer, after the results of all cohorts published in 2024 (Qi C, et al. Nat Med. 2024;30(8):2224-2234. NCT03874897). Methods: This trial is an open-label, multi-cohort, phase 1 trial, which evaluated the safety and efficacy of satri-cel in patients with CLDN18.2-positive advanced gastrointestinal cancers. Cohort 3 in dose-expansion stage enrolled patients with advance G/GEJ cancer and were given satri-cel as sequential treatment after 1L therapy. The primary endpoint was safety; secondary endpoints included efficacy, pharmacokinetics and immunogenicity. Results: As of October 18, 2025, 5 patients with CLDN18.2-positive G/GEJ cancer received satri-cel infusion(s) of 250×106 cells, sequentially after 1L therapy. Each patient received a total of one (n=1), two (n=1), and three doses (n=3) of satri-cel. Patients had received a median of 5 cycles (range, 4-11) of 1L chemotherapy before satri-cel infusion, with 1 (20%) treated with PD-1 inhibitor. Notably, only 1 patient achieved PR after first-line therapy. Three patients (60%) were Lauren diffuse type and 1 (20%) with mixed type, 4 (80%) had signet ring cell carcinoma, and 4 (80%) had peritoneal metastases. Median follow-up from initial 1L therapy was 54.6 months (reverse KM, 95% CI: 51.1, NE). Among 4 patients with target lesions, confirmatory objective response rate was 100%, and median duration of response was not reached. One has maintained SD for 20.9 months and 2 received surgical resection after satri-cel therapy. Median progression-free survival and median overall survival since 1L therapy was 20.9 months (95% CI: 10.8, NE) and 22.1 months (95% CI: 10.8, NE), respectively. Two were still alive as of cutoff date, with a follow-up of 58.1 months and 51.1 months. Safety was manageable. No grade 3 or higher cytokine release syndrome (grade 1: n=1, 20%; grade 2: n=4, 80%), any grade immune effector cell-associated neurotoxicity syndrome, or treatment-related deaths occurred. Despite common hematologic toxicities, no severe infections (grade ≥3) or febrile neutropenia were reported. Conclusions: With an extended follow-up exceeding 4.5 years, satri-cel as first-line sequential treatment continues to demonstrate durable survival benefit with a manageable safety profile in patients with advanced G/GEJ cancer, supporting its highly promising potential in earlier lines of therapy. Clinical trial information: NCT03874897 .
Liu et al. (2026) studied this question.