The first-ever randomized controlled trial (RCT) evaluating chimeric antigen receptor (CAR) T cell therapy in solid tumors has shown that the treatment significantly delays disease progression and death versus standard care in patients with gastric or gastroesophageal junction cancer.
“This is the first RCT demonstrating that a CAR-T therapy can outperform chemotherapy in a solid tumor, breaking a long-standing barrier in the field,” said first author Changsong Qi, MD, from Peking University Cancer Hospital & Institute in Beijing, China.
“The treatment, satri-cel, targets a tumor-related antigen, achieves longer survival, and maintains a tolerable safety profile,” noted Qi. “If validated in further studies and real-world settings, this therapy could redefine treatment model, offering a cellular, personalized therapy option in place of or alongside traditional systemic agents.”
Satri-cel, short for satricabtagene autoleucel, is an autologous CAR-T cell therapy that targets claudin-18 isoform 2 (CLDN18.2), a tight junction protein that is often expressed in gastric and gastro-esophageal junction adenocarcinomas but is not widely expressed in normal tissues, making it a highly specific and actionable target.
The phase II CT041-ST-01 study, conducted in China between March 2022 and July 2024, included 1566 patients with CLDN18.2-positive advanced gastric or gastro-esophageal junction cancer. They were randomly allocated to receive satri-cel (250 × 106 cells infused up to three times; n=104) or the physician’s choice of nivolumab, paclitaxel, docetaxel, irinotecan, or rivoceranib (n=52).
Qi told Inside Precision Medicine that the study originated from encouraging phase I data and a growing need to improve outcomes in advanced gastric and gastro-esophageal junction adenocarcinomas, which have limited treatment options and poor survival rates.
He reported at the 2025 ASCO Annual Meeting in Chicago that the risk for disease progression or death was a significant 63% lower among the patients given satri-cel. They had a median progression-free survival (PFS) period of 3.3 months compared with 1.8 months among those given a treatment of physician’s choice (TPC). The median follow-up times for the two groups were 9.1 and 3.5 months, respectively.
In addition, the study, which is also published in The Lancet, found that median overall survival (OS) was longer, although not significantly so, with satri-cel versus TPC, at 7.9 versus 5.5 months. The objective response rates were a corresponding 22% and 4% while the disease control rates were 63% and 25%, respectively.
The study participants were heavily pretreated; all had received at least two previous lines of treatment and 27% in the satri-cel group along with 19% in the TPC group had previously received three or more prior treatments.
“Despite being heavily pretreated, patients receiving satri-cel showed superior PFS and OS compared to chemotherapy,” said Qi. “This raises the potential that using satri-cel earlier, when patients have less tumor burden and better immune function, might yield even greater efficacy. Future trials are likely to explore satri-cel in earlier lines of therapy, possibly in combination with other agents like checkpoint inhibitors.”
Safety analyses, which included all patients who received at least one dose of study drug, revealed that 99% of 88 patients in the satri-cel group and 63% of 48 patients in the TPC group experienced grade 3 or worse treatment-emergent adverse events. In the satri-cel group these were most often decreased lymphocyte count (98%), decreased white blood cell count (77%), and decreased neutrophil count (66%). In addition, nearly all (95%) patients given satri-cel experienced cytokine release syndrome (CRS).
However, Qi said that the common toxicities, including CRS, “were mostly low-grade and manageable.”
He added that benefits of satri-cel could extend beyond improved PFS and OS. The novel treatment model means that patients only need a single or limited infusions to achieve long-term systemic disease control, while the potential for immunologic memory may contribute to prolonged disease control beyond treatment duration.
Qi believes that the success of the trial “highlights the feasibility and benefit of biomarker-driven cell therapy in solid tumors, which aligns with the goals of precision medicine—delivering the right therapy to the right patient—and could encourage further development of antigen-targeted CAR-T therapies across other solid malignancies.”
He added that future work is likely to include exploring earlier lines of therapy, exploring combination studies, broadening eligibility to include other CLDN18.2-expressing solid tumors, and optimizing manufacturing and turnaround time for broader clinical adoption.
