Satri-cel Makes Strides in Gastric and Gastroesophageal Junction Cancer

New results from the phase 2 pivotal trial of satricabtagene autoleucel (satri-cel), a Claudin18.2 (CLDN18.2)-targeting autologous CAR T-cell therapy in development by CARsgen, presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, underscore the growing potential of engineered cell therapies in solid tumors, showing positive data for patients with advanced gastric or gastroesophageal junction cancer (G/GEJC).¹

The trial (CT041-ST-01; NCT04581473), conducted in China, is the first randomized controlled trial (RCT) of a CAR T therapy in solid tumors and offers a significant benchmark for the field. The data were presented by Changsong Qi, MD, PharmD, of the Peking University Cancer Hospital, in Beijing, China. The open-label, multicenter study enrolled patients with G/GEJC who had failed at least 2 prior lines of systemic treatment. This month, Satri-cel was recently granted priority review for this specific indication by China’s National Medical Products Administration (NMPA) after receiving a breakthrough therapy designation by the agency in March.^2,3

Patients were randomly assigned in a 2:1 fashion to receive either satri-cel (n = 104) or a treatment of the physician’s choice (TPC; n = 52), including options such as apatinib, paclitaxel, docetaxel, irinotecan, or nivolumab. Patients in the TPC arm who experienced progression or drug intolerance were eligible to cross over and receive satri-cel—20 patients did so during the study period.

Satri-cel was administered at a dose of 250 × 10⁶ cells, with the possibility of up to 3 infusions per patient. The primary end point of the study was progression-free survival (PFS), as assessed by an Independent Review Committee (IRC). Secondary end points included overall survival (OS) and safety outcomes.

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Efficacy Outcomes

Across the intent-to-treat (ITT) population, treatment with satri-cel demonstrated a statistically significant improvement in PFS, with a median PFS of 3.25 months compared with 1.77 months in the TPC group (hazard ratio [HR], 0.366; 95% CI, 0.241–0.557; P < .0001). Median OS also showed a favorable trend in the satri-cel arm at 7.92 months versus 5.49 months in the TPC group (HR, 0.693; 95% CI, 0.457–1.051; one-sided P = .0416).

In the modified ITT (mITT) population, which included patients who received at least 1 dose of study treatment (satri-cel, n = 88; TPC, n = 48), outcomes were even more pronounced. The median PFS was 4.37 months with satri-cel versus 1.84 months with TPC (HR, 0.304; 95% CI, 0.195–0.474), and median OS was 8.61 months versus 5.49 months, respectively (HR, 0.601; 95% CI, 0.385–0.939).

In an exploratory analysis of all patients who received satri-cel (n = 108) versus TPC patients who did not cross over to receive satri-cel (n = 28), the median OS was 9.17 months for satri-cel versus 3.98 months for TPC alone (HR, 0.288; 95% CI, 0.169–0.492). Among the 20 TPC-arm patients who later received satri-cel, the median OS was 9.20 months, closely aligning with those treated initially with the CAR T-cell product.

Safety Outcomes

Treatment-related adverse events (TRAEs) were reported in all satri-cel recipients (100%) and 91.7% of TPC recipients. Serious TRAEs occurred in 35.2% of satri-cel patients and 25% of TPC patients. There was 1 treatment-related death in each group: 1 because of disseminated intravascular coagulation in the satri-cel arm and 1 attributed to coagulopathy in the TPC arm.

Cytokine release syndrome (CRS), a known toxicity of CAR T-cell therapies, was observed in 95.5% of satri-cel-treated patients, with the majority experiencing Grade 1-2 events (90.9%) and 4.5% experiencing Grade 3 CRS events. Importantly, no cases of immune effector cell-associated neurotoxicity syndrome (ICANS) were reported in either group.

These data mark an important advancement for CAR T-cell therapies in solid tumor indications, an area long challenged by the tumor microenvironment and antigen heterogeneity. Satri-cel’s performance in both survival and safety metrics supports its potential to become a new standard of care for patients with CLDN18.2-positive G/GEJC.

REFERENCES
1. Qi C. Claudin18.2-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). Presented at: ASCO; May 30-June 3, 2025; Chicago, IL. Abstract 4003.
2. CARsgen’s Satri-cel Granted Priority Review by the NMPA. CARsgen. News release. May 28, 2025. Accessed May 30, 2025. https://www.carsgen.com/en/news/carsgen-s-satri-cel-granted-priority-review-by-the-nmpa/
3. CARsgen’s Claudin18.2 CAR-T Therapy Satri-cel Granted Breakthrough Therapy Designation by the NMPA. CARsgen. News release. March 3, 2025. Accessed May 30, 2025. https://www.carsgen.com/en/news/20250303/