medwireNews: CAR T-cell therapy offers significantly longer progression-free survival (PFS) in patients previously treated for advanced gastric or gastro-oesophageal junction cancer compared with a physician’s choice of treatment, report Chinese investigators.
The open-label phase 2 trial 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.
“Our study is, to the best of our knowledge, the world’s first randomised controlled trial of a CAR T-cell therapy for solid tumours,” write Changsong Qi (Peking University Cancer Hospital & Institute, Beijing) and fellow CT041-ST-01 investigators.
They say their findings suggest 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 study included 266 patients with advanced disease refractory to at least two lines of therapy, all of whom had confirmed expression of the tight junction molecule claudin-18 isoform (CLDN18.2), defined as 2+ or stronger immunohistochemistry and at least 40% positive tumor cells.
Patients assigned to receive up to three infusions of satri-cel therapy underwent apheresis and one cycle of bridging therapy with irinotecan or irinotecan plus fluorouracil, followed by lymphodepletion before each infusion of 250 x 106 cells. Participants given physician’s choice of chemotherapy received nivolumab, paclitaxel, docetaxel, irinotecan, or apatinib, with satri-cel then offered to those unable to tolerate treatment or who experienced progressive disease.
Overall, 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 of 9.1 and 3.5 months, respectively, and for overall survival (OS) for 14.4 and 11.3 months, respectively.
Intention-to-treat analysis indicated that 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, and although this difference did not reach statistical significance, the investigators described the finding as being “clinically meaningful.”
In addition, satri-cel offered improvements over physician’s choice of treatment in the rates of objective response (22 vs 4%) and disease control (63 vs 25%) but a comparable duration of response (median 5.5 vs 4.9 months).
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 patients given physician’s choice of therapy.
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.
Qi and co-authors summarize that satri-cel had a “manageable safety profile” and postulate 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.”
They 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
2025 ASCO Annual Meeting; Chicago, Illinois, USA: 30 May–3 June