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
The first randomised trial of CAR-T cells in a solid tumour: in heavily pretreated Claudin 18.2-positive stomach cancer, satri-cel held the disease for a median of 3.25 months against 1.77 months on the doctor's choice of drug, with almost universal cytokine release syndrome.
Overview
Open-label, multicentre, randomised controlled phase 2 trial in China in patients with CLDN18.2-positive (immunohistochemistry intensity at least 2+ and at least 40 percent positive tumour cells) advanced gastric or gastro-oesophageal junction cancer refractory to at least two previous lines. Patients were randomly allocated 2:1 to satri-cel (up to three infusions of 250 million cells) or treatment of physician's choice (nivolumab, paclitaxel, docetaxel, irinotecan or rivoceranib), with crossover to satri-cel allowed after progression or intolerance. The primary endpoint was progression-free survival by independent review committee in the intention-to-treat population.
Between March 2022 and July 2024, 266 patients were screened and 156 randomised (104 satri-cel, 52 physician's choice); 88 (85 percent) and 48 (92 percent) received study drug. Median progression-free survival was 3.25 months (95% CI 2.86 to 4.53) with satri-cel and 1.77 months (95% CI 1.61 to 2.04) with physician's choice (hazard ratio 0.37, 95% CI 0.24 to 0.56; one-sided log-rank p<0.0001). Grade 3 or higher treatment-emergent adverse events occurred in 87 of 88 (99 percent) treated satri-cel patients and 30 of 48 (63 percent) on physician's choice; cytokine release syndrome occurred in 84 of 88 (95 percent). Funded by CARsgen Therapeutics.
- Median progression-free survival 3.25 vs 1.77 months; hazard ratio 0.37 (95% CI 0.24 to 0.56), one-sided log-rank p<0.0001.
- 156 randomised of 266 screened; 85% of the satri-cel arm and 92% of the physician's choice arm received study drug.
- Grade 3 or higher treatment-emergent adverse events in 99% vs 63% of treated patients; cytokine release syndrome in 95% of treated satri-cel patients.
This is the trial behind the first approval of a CAR-T therapy for a solid tumour, in China. The gain in progression-free survival is real but measured in weeks, 15 percent of patients randomised to satri-cel never received it, and nearly every treated patient had cytokine release syndrome, so the trade-off is very different from CAR-T in blood cancers. Overall survival is not reported in the abstract.
- Open-label, 2:1 randomisation, and crossover from physician's choice to satri-cel was allowed, which complicates any later survival comparison.
- The abstract reports no overall survival figures.
- Requires Claudin 18.2 testing by immunohistochemistry and manufacturing time; 16 of 104 randomised patients did not receive satri-cel.
Similar pages
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