By Lynda Williams, medwireNews Reporter
medwireNews: The first randomised controlled trial of a CAR T-cell therapy in solid tumours has achieved a significant improvement in progression-free survival (PFS) for patients with advanced gastric or gastro-oesophageal junction cancer compared with physician’s choice of therapy.
The open-label phase 2 study of satricabtagene autoleucel (satri-cel) was published in The Lancet to coincide with its presentation at the 2025 ASCO Annual Meeting in Chicago, Illinois, USA, by author Changsong Qi, from Peking University Cancer Hospital & Institute in Beijing, China.
“These results indicated that satri-cel could become the standard care for these pretreated patients and support its further investigation in earlier treatment lines for advanced gastric or gastro-oesophageal junction cancer”, the CT041-ST-01 trial investigators write.
The study recruited 266 patients with advanced disease refractory to at least two lines of therapy and confirmed expression of the tight junction molecule claudin-18 isoform (CLDN18.2), with 2+ or stronger immunohistochemistry findings and at least 40% positive tumour cells.
Satri-cel therapy consisted of apheresis and one cycle of bridging therapy with irinotecan or irinotecan plus fluorouracil, followed by lymphodepletion before each infusion of 250 x 106 cells, with up to three infusions given. Physician’s choice consisted of nivolumab, paclitaxel, docetaxel, irinotecan, or apatinib, followed by satri-cel for those with progressive disease or treatment intolerance.
The researchers note that 27% of the 104 patients in the satri-cel arm had received at least three lines of treatment and 69% had peritoneal metastases compared with a respective 19% and 60% of the 52 patients instead given physician’s choice of treatment. Study treatment was received by 85% and 92% of the satri-cel and physician’s choice groups, respectively.
The satri-cel and physician’s choice groups were followed up for PFS for a median 9.1 and 3.5 months, respectively, and for overall survival (OS) for 14.4 and 11.3 months, respectively.
By intention-to-treat analysis, the median PFS was 3.3 months with satri-cel – significantly longer than the median 1.8 months with physician’s choice of therapy (hazard ratio=0.37). Median OS was numerically longer with satri-cel, at 7.9 months versus 5.5 months with physician’s choice, which the researchers describe as “clinically meaningful” despite the difference not reaching statistical significance.
Compared with physician’s choice of therapy, satri-cel was also associated with higher rates of objective response (22 vs 4%) and disease control (63 vs 25%), although duration of response was comparable (median 5.5 vs 4.9 months).
Qi and co-authors say that satri-cel had a “manageable safety profile”. Among the safety population of patients who received at least one dose of their study drug, 99% of the 88 patients in the satri-cel arm had a grade 3 or more severe treatment-emergent adverse event (AE) compared with 63% of 48 controls.
The most common grade 3 or more severe treatment-related AEs with satri-cel were decreased levels of lymphocytes (98%), white blood cells (77%) and neutrophils (66%). Cytokine release syndrome at any grade was reported for 95% of patients and at grade 3 or worse for 5%. There were no cases of immune effector cell-associated neurotoxicity syndrome.
One patient given satri-cell died from disseminated intravascular coagulation related to treatment and one patient given physician’s choice of therapy died from coagulopathy.
“The available data indicate that satri-cel could represent a paradigm shift in managing advanced gastric or gastro-oesophageal junction adenocarcinomas, addressing a crucial unmet need for these patients”, Qi et al conclude.
“Satri-cel’s benefits over conventional regimens validate CAR T-cell therapy as a viable modality in solid tumours and support its integration into third-line treatment guidelines.”
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Lancet 2025; doi:10.1016/ S0140-6736(25)00860-8
https://pubmed.ncbi.nlm.nih.gov/40460847
Keywords: CAR T-cell therapy, gastric cancer, gastro-oesophageal junction cancer