Satri-Cel NDA Gets Go-Ahead From NMPA in Pretreated CLDN18.2+ Advanced Gastric/GEJ Cancer

Satri-Cel in CLDN18.2+ Advanced Gastric/GEJ Cancer

| Image by Ashling Wahner & MJH Life Sciences Using AI

China’s National Medical Products Administration (NMPA) has accepted the new drug application (NDA) seeking the approval of the investigational autologous CAR T-cell agent satricabtagene autoleucel (satri-cel; CT041) for the treatment of patients with Claudin18.2 (CLDN18.2)–positive gastric/gastroesophageal junction (GEJ) cancer following disease progression on at least 2 prior lines of therapy.1

The NDA submission was mainly supported by data from the phase 2 CT041-ST-01 trial (NCT04581473). Findings from CT041-ST-01 presented during the 2025 ASCO Annual Meeting and subsequently published in The Lancet demonstrated that patients who received satri-cel (n = 104) achieved a median progression-free survival (PFS) per independent review committee (IRC) assessment of 3.25 months (95% CI, 2.86-4.53) compared with 1.77 months (95% CI, 1.61-2.04) among those treated with physician’s choice of therapy (n = 52; HR, 0.366; 95% CI, 0.241-0.557; 1-sided P < .0001).2 The 6-month PFS rates were 24% and 18%, respectively.

Moreover, the median overall survival (OS) in the investigational arm was 7.92 months (95% CI, 5.78-10.02) vs 5.49 months (95% CI, 3.94-6.93) in the control arm (HR, 0.693; 95% CI, 0.457-1.051; 1-sided P = .0416). The 18-month OS rates were 20% and 10%, respectively.

“Gastric cancer is a malignancy with a substantial global disease burden and significant treatment challenges,” Lin Shen, MD, an oncologist at Beijing Cancer Hospital in China and the principal investigator of CT041-ST-01, stated in a news release.1 “For patients with advanced gastric cancer, in particular, existing therapeutic options and their efficacy remain severely limited, resulting in extremely poor survival outcomes. Within the current treatment landscape for gastric cancer, a growing number of patients have experienced failure with immunotherapy and anti-angiogenic therapies. Treatment choices and potential benefits become even more constrained in the third-line setting and beyond. Consequently, there exists a significant unmet clinical need for [patients with] advanced gastric cancer after second-line treatment failure. The confirmatory randomized controlled clinical trial of satri-cel has clearly demonstrated that, compared with existing standard therapies, satri-cel offers significant advantages and clinical value in extending both PFS and OS. The trial results have garnered widespread international attention and recognition, providing a solid evidentiary foundation for satri-cel’s NDA submission. We look forward to the approval and market launch of satri-cel, which will offer a new treatment option for the broader population of [patients with] gastric cancer.”

CT041-ST-01 was an open-label, multicenter study that enrolled patients between the ages of 18 and 75 years with advanced gastric/GEJ cancer who had experienced disease progression following at least 2 prior lines of therapy.2 Patients were also required to have at least 1 measurable lesion, an ECOG performance status of 0 or 1, CLDN18.2 expression of 2+ or 3+ by immunohistochemistry on at least 40% of tumor cells, and HER2-negative disease.

Eligible patients were randomly assigned 2:1 to receive satri-cel at a dose of 250 × 106 cells following apheresis, bridging therapy, and lymphodepletion; or physician’s choice of treatment after apheresis. Reinfusion with satri-cel up to 3 times was permitted. Physicians chose between apatinib (Aitan), paclitaxel, docetaxel, irinotecan, or nivolumab (Opdivo) for the control therapies. If eligible, patients in the control arm were allowed to cross over to receive satri-cel following events including disease progression or intolerable toxicity.

The primary end point was IRC-assessed PFS. OS represented the key secondary end point; other secondary end points included investigator-assessed PFS, overall response rate (ORR), duration of response, and safety.

Additional findings from CT041-ST-01 revealed that the IRC-assessed ORR among patients with measurable disease in the satri-cel arm of the modified intention-to-treat population (mITT; n = 76) was 30% (95% CI, 20%-42%), and the disease control rate was 70% (95% CI, 58%-80%). These respective rates among patients with measurable disease in the control arm of the mITT population (n = 45) were 4% (95% CI, 1%-15%) and 24% (95% CI, 13%-40%).

Regarding safety, evaluable patients in both the investigational (n = 88) and control (n = 48) arms experience any-grade treatment-emergent adverse effects (TEAEs; 100% vs 91.7%), TEAEs related to treatment (100% vs 91.7%), and treatment-related AEs leading to death (1.1% vs 2.1%). No patients in the satri-cel group experienced TEAEs leading to treatment discontinuation, and there were no instances of immune effector cell–associated neurotoxicity syndrome in either arm. Most patients in the satri-cel arm experienced any-grade cytokine release syndrome (CRS; 95.5%); 4.5% of patients in this arm had grade 3 or higher CRS.

“We are delighted to announce that the NDA for our self-developed CLDN18.2-targeted CAR T-cell product satri-cel has been accepted for review by China’s NMPA,” Zonghai Li, MD, founder, chairman of the board, chief executive officer, and chief scientific officer of CARsgen Therapeutics, added in the news release.1 This marks the world's first CAR T-cell therapy product for solid tumors to reach the NDA stage—a major milestone for the CAR T field. I extend my sincere gratitude to all clinical investigators, trial coordinators, and patients involved in this program. We are hopeful for its timely approval to provide [patients with] gastric cancer with a new treatment option.”

References

1. CARsgen Therapeutics announces NDA acceptance of satri-cel by China’s NMPA. News release. CARsgen Therapeutics. June 26, 2025. Accessed June 26, 2025. https://www.carsgen.com/en/news/20250626/
2. Qi C, Liu C, Peng Z, et al. 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). J Clin Oncol. 2025;43(suppl 16):4003. doi:10.1200/JCO.2025.43.16_suppl.4003