Satricabtagene autoleucel (CT041; satri-cel; CARsgen Therapeutics), an autologous chimeric antigen receptor (CAR) T-cell product candidate against protein Claudin18.2, improves progression-free survival (PFS) and overall survival (OS) compared with treatment of the physician’s choice (TPC) in patients diagnosed with advanced gastric or gastroesophageal junction (GEJ) cancer who have received two or more prior lines of therapy.
Claudin18.2-redirected CAR T cells Have Demonstrated promising efficacy against gastric cancer, significantly improving progression-free survival and overall survival
This is the conclusion of study results presented at the annual meeting of the American Society of Clinical Oncology (ASCO), held May 30-June 3, 2025, in Chicago, Illinois [Abstract 4003], which was simultaneously published in The Lancet [1][2]
A million new cases
Each year, approximately one million new cases of gastric cancer, diseases of malignant glandular cells, are diagnosed worldwide. And despite recent advances in treatment options, relapse is inevitable, and patients become refractory to treatment.[3][4]
According to recent data, the five-year survival for patients diagnosed with advanced gastric cancer is about 5–20% and the median overall survival is about 10 months [3][4][5]
The poor prognosis of these two cancer types highlights the need for additional treatment approaches.
Incidence in China
In 2020, there were 480,000 new cases of gastric cancer in China, accounting for 43.9% of the total incidence globally. Moreover, there is a rising trend in the incidence of gastric cancer among young people.
Claudin18.2 (CLDN18.2) is highly expressed in various malignant tumors, especially gastrointestinal cancers, and has been recognized as a new target for cancer treatment.
Satricabtagene autoleucel
Satricabtagene autoleucel contains genetically engineered autologous T cells designed to express a chimeric antigen receptor (CAR) targeting CLDN18.2. The CAR structure consists of a humanized anti-CLDN18.2 single-chain variable fragment, a CD8α hinge region, a CD28 co-stimulatory domain, and a CD3ζ signaling domain.[6][7]
Study design
In an open-label, multicenter, randomized controlled trial (NCT04581473) conducted in China, researchers compared the efficacy and safety of satricabtagene autoleucel versus standard of care (SOC) in CLDN18.2-positive, advanced G/GEJC patients who had failed at least 2 prior lines of treatment. The primary endpoint was PFS assessed by the Independent Review Committee (IRC). The key secondary endpoint was OS. The data cutoff date was October 18, 2024.
In the study, patients were randomized (2:1) to the satricabtagene autoleucel arm or to the physician’s treatment of choice (TPC arm). For the satricabtagene autoleucel arm, a dose of 250×106 cells was infused up to 3 times. For the TPC arm, one of the standard-of-care (SOC) drugs (apatinib, paclitaxel, docetaxel, irinotecan, or nivolumab) was administered at the physician’s discretion. Those who experienced disease progression or drug intolerance in the TPC arm could receive subsequent satricabtagene autoleucel, if eligible.
From March 29, 2022, to Aug 16, 2024, a total of 156 patients were randomized to the satricabtagene autoleucel arm (n = 104) or the TPC arm (n = 52). Twenty patients in TPC arm received subsequent satricabtagene autoleucel. Median number of prior systemic therapies was 2 in both arms, and 26.9% vs 19.2% had received ≥3 lines. 71.2% vs 65.4% were Lauren diffuse/mixed type. 69.2% vs 59.6% had peritoneal metastasis.
In the intent to treat (ITT) population (i.e., all randomized patients), satricabtagene autoleucel showed significant improvement in mPFS by IRC (3.25m vs 1.77m; HR 0.366, 95% CI:0.241, 0.557; p < 0.0001), meeting the primary endpoint with a 63% reduction in risk of disease progression or death. Even with 15.4% (n=16) patients in satri-cel arm failing to receive infusion and nearly 40% (n=20) patients in TPC arm receiving subsequent satri-cel, satri-cel arm still demonstrated a clear trend toward OS benefit (mOS 7.92m vs 5.49m; HR 0.693, 95% CI: 0.457, 1.051; one-sided p = 0.0416) , showing over 30% reduction in mortality risk.
More importantly, in mITT population (i.e. patients who were actually treated), 136 patients received satricabtagene autoleucel (88 patients vs TPC 48 patients), mPFS by IRC was 4.37m vs 1.84m, HR 0.304 (95% CI: 0.195, 0.474), representing a 70% reduction in risk of disease progression or death. The mOS was 8.61m vs 5.49m, HR 0.601 (95%CI: 0.385, 0.939), corresponding to 40% reduction in mortality risk.
These results demonstrate that the benefits of satricabtagene autoleucel treatment were pronounced in patients who actually received the CAR-T infusion.
Of particular note, 20 TPC patients with subsequent satri-cel infusion achieved an mOS of 9.20 months. When analyzing all 108 patients who received satri-cel infusion (88 patients in satricabtagene autoleucel arm and 20 patients in TPC arm), the mOS reached 9.17 months, while the mOS of 28 patients in TPC arm who did not receive satricabtagene autoleucel treatment was only 3.98 months (HR 0.288; 95% CI: 0.169-0.492). These findings provide further evidence that satri-cel infusion can deliver substantial survival benefits for patients.
Furthermore, satricabtagene autoleucel demonstrated a favorable overall safety profile. Only 4 cases of Grade 3 cytokine release syndrome (CRS) were reported, and no Grade 4-5 CRS events were observed. No immune effector cell-associated neurotoxicity syndrome (ICANS) was reported.
This is the first confirmatory RCT of CAR-T therapy in solid tumors. Satricabtagene autoleucel demonstrated significant PFS improvement and a clinically meaningful OS benefit with a manageable safety profile in CLDN18.2 positive G/GEJC patients with failure to at least 2 prior lines of treatment, compared to standard therapy. These results support satri-cel as a potential new SOC for advanced G/GEJC.
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Clinical trials
Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of CT041 Autologous CAR T-cell Injection – ClinicalTrials.gov ID NCT04581473
Chimeric Antigen Receptor T Cells Targeting claudin18.2 in Solid Tumors. – ClinicalTrials.gov ID NCT03874897
Postoperative Adjuvant Therapy for CT041 Gastric or Gastroesophageal Junction (G/GEJ) Adenocarcinoma Patients (CT041-CG4010) – ClinicalTrials.gov ID NCT06857786
Reference
[1] Qi C, Liu C, Peng Z, Zhang Y, Wei J, Qiu W, Zhang X, Pan H, Niu Z, Qiu M, Qin Y, Fang W, Ye F, Li N, Liu T, Wang Y, Yuan D, Li Z, Shen L. Claudin 18.2-specific CAR T cells (Satri-cel) versus treatment of physician’s choice (TPC) for previously treated advanced gastric or gastroesophageal junction cancer (G/GEJC): Primary results from a randomized, open-label, phase II trial (CT041-ST-01). J Clin Oncol 43, 4003-4003(2025). DOI: 10.1200/JCO.2025.43.16_suppl.4003
[2] Qi C, Liu C, Peng Z, Zhang Y, Wei J, Qiu W, Zhang X, Pan H, Niu Z, Qiu M, Qin Y, Fang W, Ye F, Li N, Liu T, Liu A, Zhang X, Hu C, Zhang J, Cui J, Lin X, Wang S, Zhang J, Lin T, Qu X, Yuan X, Gong J, Li J, Gao W, Gai L, Wang Y, Yuan D, Li Z, Shen L. 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. Lancet. 2025 Jun 7;405(10494):2049-2060. doi: 10.1016/S0140-6736(25)00860-8. Epub 2025 May 31. PMID: 40460847.
[3]Kumar V, Soni P, Garg M, Kamholz S, Chandra AB. Emerging Therapies in the Management of Advanced-Stage Gastric Cancer. Front Pharmacol. 2018 Sep 13;9:404. doi: 10.3389/fphar.2018.00404. PMID: 30271341; PMCID: PMC6146175.
[4] Sitarz R, Skierucha M, Mielko J, Offerhaus GJA, Maciejewski R, Polkowski WP. Gastric cancer: epidemiology, prevention, classification, and treatment. Cancer Manag Res. 2018 Feb 7;10:239-248. doi: 10.2147/CMAR.S149619. PMID: 29445300; PMCID: PMC5808709.
[5] Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. PMID: 30207593.
[6] Qi C, Gong J, Li J, Liu D, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Cao Y, Zhang X, Lu Z, Lu M, Yuan J, Wang Z, Wang Y, Peng X, Gao H, Liu Z, Wang H, Yuan D, Xiao J, Ma H, Wang W, Li Z, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial interim results. Nat Med. 2022 Jun;28(6):1189-1198. doi: 10.1038/s41591-022-01800-8. Epub 2022 May 9. PMID: 35534566; PMCID: PMC9205778.
[7] Qi C, Liu C, Gong J, Liu D, Wang X, Zhang P, Qin Y, Ge S, Zhang M, Peng Z, Zhou J, Lu Z, Lu M, Cao Y, Yuan J, Wang Y, Wang Z, Xue R, Peng X, Wang Y, Yuan D, Li J, Zhang X, Shen L. Claudin18.2-specific CAR T cells in gastrointestinal cancers: phase 1 trial final results. Nat Med. 2024 Aug;30(8):2224-2234. doi: 10.1038/s41591-024-03037-z. Epub 2024 Jun 3. PMID: 38830992.
Featured image: 2016 ASCO Annual Meeting. Photo courtesy: © 2026 – 2025 ASCO/Todd Buchanan. Used with permission.
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