Satri-cel, a CLDN18.2-targeted CAR T-cell therapy, nearly doubles progression-free survival in patients with previously treated gastric or gastro-esophageal junction cancer, according to a multicenter randomized trial led by Peking University Cancer Hospital in China.

Gastric and gastro-esophageal junction cancers remain among the deadliest malignancies worldwide. Most patients with advanced disease do not respond to existing second-line therapies, and survival after standard treatment failure is typically short. While targeted therapies have improved first-line options, their efficacy often relies on ongoing chemotherapy, which introduces cumulative toxicity and limits durability.

Claudin-18 isoform 2 (CLDN18.2), expressed in approximately 40% of gastric tumors, has emerged as a target of interest. CLDN18.2 is a tight-junction protein variant normally expressed only in differentiated epithelial cells of the gastric mucosa. Under healthy conditions, CLDN18.2 is sequestered within cell–cell junctions, making it inaccessible to systemic agents.

Unlike its protected status in healthy gastric cells, the structural integrity of CLDN18.2 is often poorly replicated in cancerous tissue, making it accessible to monoclonal antibodies and CAR T-cell therapies.

Unlike monoclonal antibodies or chemotherapy-based regimens, satri-cel uses live, reprogrammed immune cells from each patient’s own T cells to attack solid tumors directly. These cells are collected from the patient, genetically modified ex vivo to attack CLDN18.2, expanded in number, and then reinfused into the patient following lymphodepleting chemotherapy.

In the study, “Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician’s choice for previously treated advanced gastric or gastro-esophageal junction cancer (CT041-ST-01),” published in The Lancet, researchers designed a randomized Phase II trial to assess whether satri-cel could extend survival compared to conventional treatments.

A total of 156 patients with advanced, HER2-negative, CLDN18.2-positive gastric or gastro-esophageal junction cancer were enrolled across 24 Chinese hospitals. All had previously failed at least two systemic therapies. Participants were randomly assigned in a 2:1 ratio to receive either up to three infusions of satri-cel or one of five standard drugs selected by their physician.

Median progression-free survival in the satri-cel group was 3.25 months, compared with 1.77 months in the control group. Overall survival was also longer in the satri-cel group at 7.92 vs. 5.49 months. Among those who received satri-cel, the objective response rate was 22%, and the disease control rate reached 63%. Notably, satri-cel showed benefit across key subgroups, including patients with peritoneal metastases.

Adverse events were frequent and mostly hematologic. Grade 3 or higher events occurred in 99% of satri-cel recipients, with cytokine release syndrome in 95%. Most commonly, patients had decreased lymphocyte counts (98%), cytokine release syndrome (95%), and lowered white cell counts (77%). One death in each group was attributed to treatment-related toxicity.

Authors note that 16 satri-cel-assigned patients never received infusion due to rapid disease progression, pointing to challenges in treating fast-moving cancers with cell therapies that require manufacturing delays.

Researchers conclude that satri-cel could represent a viable third-line treatment for advanced CLDN18.2-positive gastric or gastro-esophageal cancer, and a breakthrough in extending CAR T-cell therapy beyond hematologic malignancies.

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