On June 1, 2025, the world's first randomized controlled trial (RCT) of CAR-T therapy for gastric cancer—"Claudin-18 isoform 2-specific CAR T-cell therapy (satri-cel) versus treatment of physician’s choice for previously treated advanced gastric or gastro-oesophageal junction cancer (CT041-ST-01): a randomised, open-label, phase 2 trial"—designed and led by Prof. Lin Shen’s team, was officially published in the prestigious international journal The Lancet (Impact Factor = 168.9). The study’s first author, Prof. Changsong Qi, also presented the positive findings in an oral session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, drawing widespread attention.

On June 3, the study results also made the headline on Nature’s official website.

 

Background

The CT041-ST-01 trial (NCT04581473) is the first randomized controlled clinical trial globally of CAR-T therapy targeting solid tumors. It evaluated the efficacy and safety of Satricabtagene Autoleucel (satri-cel)—a CLDN18.2-specific autologous CAR-T cell therapy—versus treatment of physician’s choice (TPC) in patients with previously treated advanced gastric or gastroesophageal junction cancer (G/GEJC).

CLDN18.2 is overexpressed in several gastrointestinal cancers and has emerged as a promising therapeutic target, especially in G/GEJC. Satri-cel showed encouraging results in a prior phase 1 trial involving patients with advanced G/GEJC who had failed standard therapies. The breakthrough results were published by Prof. Shen's team in Nature Medicine in June 2024 (Qi, C. et al. Nat. Med. 2024. doi: 10.1038/s41591-024-03037-z), laying a strong scientific foundation for advancing CAR-T in solid tumors. Building on these findings, the team launched the confirmatory phase 2 trial in CLDN18.2-positive G/GEJC patients who had failed at least two prior lines of therapy.

 

Study Design

This phase 2, open-label, multicenter, randomized controlled trial was conducted in China to compare the efficacy and safety of satri-cel versus standard therapies in CLDN18.2-positive (≥40% tumor cells with membrane staining intensity ≥2+) advanced G/GEJC patients who had failed at least two prior lines of therapy.

Eligible patients were randomized in a 2:1 ratio to receive:

• Satricel group: up to 3 infusions of satri-cel (2.5×10^8 cells per infusion),
• TPC group: treatment of physician’s choice (paclitaxel, docetaxel, irinotecan, nivolumab, or apatinib).
  TPC patients were allowed to cross over to receive CT041 upon progression or intolerance, at the investigator’s discretion.

The primary endpoint was progression-free survival (PFS) assessed by Independent Review Committee (IRC). The key secondary endpoint was overall survival (OS).

 

Results

As of October 18, 2024, a total of 156 patients were randomized into the study, comprising the intent-to-treat (ITT) population, including 104 patients in the satri-cel group and 52 patients in the treatment of physician’s choice (TPC) group. A total of 88 patients (84.6%) in the satri-cel group and 48 patients (92.3%) in the TPC group received the study treatment, forming the modified intent-to-treat (mITT) population. Among them, 20 patients in the TPC group subsequently received CT041 infusion. All participants had previously received at least two lines of therapy, with 26.9% in the satri-cel group and 19.2% in the TPC group having received three or more lines. The proportion of peritoneal metastasis was 69.2% vs 59.6%, respectively.

In the ITT population:
Based on evaluation by the Independent Review Committee (IRC), satri-cel significantly prolonged progression-free survival (PFS) compared to the control group (median PFS: 3.25 months vs 1.77 months; HR: 0.37, 95% CI: 0.24–0.56; p < 0.0001), achieving the primary endpoint of the study. At the same time, overall survival (OS) showed a clear trend toward benefit (median OS: 7.92 months vs 5.49 months; HR: 0.69, 95% CI: 0.46–1.05; one-sided p = 0.0416). Notably, even with 15.4% (16 patients) in the satri-cel group not receiving cell infusion and approximately 40% (20 patients) in the TPC group later receiving satri-cel, the CT041 group still demonstrated over 30% reduction in mortality risk.

Primary Endpoint Achieved: PFS in ITT Population Shows Positive Results

 

In the mITT population (patients who actually received treatment): Based on IRC evaluation, median PFS in the satri-cel and TPC groups was 4.37 months vs 1.84 months (HR: 0.30, 95% CI: 0.19–0.47); median OS was 8.61 months vs 5.49 months (HR: 0.60, 95% CI: 0.38–0.94).
Therefore, among patients who actually received cell infusion, the therapeutic benefit of CT041 was even more pronounced.

It is worth noting that the median OS among the 20 TPC patients who subsequently received satri-cel was 9.20 months. Among all patients who received satri-cel infusion (n=108) from both groups, the median OS reached 9.17 months.

In terms of safety, satri-cel was generally well tolerated. Only 4 patients experienced grade 3 cytokine release syndrome (CRS); no grade 4 or 5 CRS occurred. No immune effector cell-associated neurotoxicity syndrome (ICANS) events were reported.

 

Conclusion

This study represents the first confirmatory randomized controlled trial of CAR-T therapy for solid tumors globally and marks a milestone in the field.

In CLDN18.2-positive G/GEJC patients who had failed at least two prior treatments, satri-cel significantly improved PFS and showed clinically meaningful OS benefits, with a manageable safety profile. The results strongly support satri-cel as a new third-line standard of care for advanced CLDN18.2-positive G/GEJC.

 

At the ASCO 2025 oral presentation, Prof. Changsong Qi told media:

"These results suggest that CLDN18.2 CAR-T therapy could transform the treatment landscape for advanced gastric cancer and offer a nearly unprecedented cell therapy option for solid tumors."