Satri-cel Improves Survival vs Physician’s Choice in Pretreated G/GEJ Cancer

The confirmed objective response rate per independent review committee was 22% with satri-cel vs 4% with treatment of physician’s choice.

Satricabtagene autoleucel (satri-cel) significantly improved progression-free survival (PFS) while maintaining a manageable safety profile in the third-line treatment of patients with advanced gastric or gastroesophageal junction (G/GEJ) cancer, according to results from the phase 2 CT041-ST-01 trial (NCT04581473), the first randomized controlled trial of CAR T-cell therapy in solid tumors globally, published in The Lancet.¹

In the intention-to-treat population, the median PFS was 3.25 months (95% CI, 2.86-4.53) with satri-cel vs 1.77 months (95% CI, 1.61-2.04) with treatment of physician’s choice (HR, 0.37; 95% CI, 0.24-0.56; P <.0001). As a result of the trial meeting the prespecified criteria for PFS superiority with satri-cel, the final analysis of overall survival (OS) was done. The median OS was 7.92 months (95% CI, 5.78-10.02) with satri-cel vs 5.49 months (95% CI, 3.94-6.93) with treatment of physician’s choice (HR, 0.69; 95% CI, 0.46-1.05; P = .0416). Across prespecified subgroups, satri-cel was favorable regarding both PFS and OS.

Based on the reverse Kaplan-Meier method, the median follow-up times for PFS were 9.07 months in the satri-cel group and 3.45 months in the treatment of physician’s choice group; the median follow-up times for OS were 14.42 months vs 11.33 months.

The confirmed objective response rate (ORR) per independent review committee was 22% (95% CI, 15%-31%) with satri-cel vs 4% (95% CI, 0%-13%) with treatment of physician’s choice; the disease control rate (DCR) was 63% (95% CI, 52%-72%) vs 25% (95% CI, 14%-39%), respectively.

The median duration of response was 5.52 months (95% CI, 2.79-12.02) with satri-cel, and in the treatment of physician’s choice group, 2 patients had partial responses with durations of 4.47 months and 5.42 months. Regarding the median time to response, the satri-cel group demonstrated a time of 1.94 months (95% CI, 1.87-3.25), while the 2 patients who responded to treatment of physician’s choice had times of 1.77 months and 2.96 months. Those who received treatment of physician’s choice experienced a longer median duration of disease control vs those who received satri-cel (4.27 months vs 3.61 months).

“Globally, this is the first randomized controlled study of a CAR T-cell therapy in solid tumors and the first to demonstrate the superiority of CAR T-cell therapy vs standard of care,” wrote lead study author Lin Shen, MD, of the Beijing Key Laboratory of Cell and Gene Therapy for Solid Tumors, State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, in Beijing, China, in the paper with study coinvestigators.¹ “These data suggest that satri-cel could become a new treatment option for this patient population, and provide a strong rationale for continued investigation of satri-cel in earlier lines of treatment for patients with advanced [G/GEJ] cancer.”

A total of 156 patients were randomly assigned, in a 2:1 ratio, to receive either satri-cel at 250 x 10⁶ cells via intravenous infusion up to 3 times (n = 104) or treatment of physician’s choice consisting of nivolumab (Opdivo), paclitaxel, docetaxel, rivoceranib (Apatanib), or irinotecan (n = 52). Those who progressed on treatment of physician’s choice were permitted to receive subsequent satri-cel.

Prior to satri-cel treatment, patients were allowed to receive 1 cycle of bridging therapy with intravenous irinotecan or a combination of intravenous fluorouracil and irinotecan. Before each satri-cel infusion, patients received a lymphodepletion regimen including fludarabine, cyclophosphamide, and nab-paclitaxel.

Patients 18 to 75 years of age with pathologically confirmed advanced G/GEJ cancer had tumor tissue samples with positive immunohistochemical staining for Claudin-18 isoform 2 (CLDN18.2) and negative staining for HER2 collected. They were refractory on at least 2 prior lines of treatment, had at least 1 measurable lesion per RECIST v1.1, and had an ECOG performance status of 0 or 1. Those who received previous anti-CLDN18.2 therapy were required to receive CLDN18.2 expression reassessment.

The trial’s primary end point was PFS per blinded independent review committee. Secondary end points included OS, PFS by investigator assessment, ORR, DOR, DCR, and safety.

In the safety analysis set consisting of all patients who received at least 1 dose of the study drug, treatment-emergent adverse events (TEAEs) of grade 3 or higher occurred in 99% of the satri-cel group and 63% of the treatment of physician’s choice group; the most common TEAEs in the satri-cel group were decreased lymphocyte count (99%), decreased white blood cell count (98%), and cytokine release syndrome (95%). Treatment-related AEs led to death in 1 patient for both groups, due to disseminated intravascular coagulation in the satri-cel group and coagulopathy in the treatment of physician’s choice group.

In a press release on trial results shared at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, Muhammad Shaalan Beg, MD, MBA, FASCO, of the University of Texas Southwestern Medical Center, and ASCO Daily News Associate Editor, stated, “The [phase 2 CT041-ST-01] trial met its primary endpoint of PFS, with patients receiving satri-cel showing significant improvement in median PFS by independent review. CAR T-cell therapies have largely been ineffective in treating solid malignancies, and this is the first positive randomized trial of CAR T-cell cell therapy in solid tumors.”²

Reference

1. Qi C, Liu C, Peng Z, et al. 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;405(e10494):P2049-2060. doi:10.1016/S0140-6736(25)00860-8
2. Satricabtagene autoleucel yields PFS and OS benefit in advanced gastric and gastroesophageal junction cancer. News release. ASCO Daily News. May 31, 2025. Accessed June 9, 2025. https://tinyurl.com/p7bh6p99