First CLDN18.2-Targeted CAR-T Success in Gastric Cancer Presented at ASCO 2025

CAR T-Cell Therapies Are No Longer Limited to Blood Cancers!

One of the most remarkable successes of personalized medicine, CAR T-cell therapy, has revolutionized the treatment of hematological cancers over the past 10 years. In this cellular treatment model, the patient's own immune cells, T lymphocytes, are genetically modified and equipped with chimeric antigen receptors (CARs) that specifically target cancer cells. These cells are then expanded in the laboratory and returned to the patient, where they are expected to recognize and destroy tumor cells directly.

First approved by the FDA in 2017, CAR T-cell therapies have achieved impressive success, particularly in resistant or recurrent hematological cancers. Remissions in which patients remain completely disease-free for years are considered a milestone in modern oncology.

🩸 A Wave of Approvals in Hematological Cancers

• CD19-targeted CAR T cells: have revolutionized B-cell hematological malignancies such as ALL and DLBCL.
• BCMA-targeted CAR T cells: are used in multiple myeloma in patients who have not responded to many prior lines of therapy.

🧱 Why Are Solid Tumors More Challenging?

1. Target antigen selection: Finding a highly specific target in solid tumors is difficult.
2. Tumor microenvironment: Solid tumors are surrounded by a microenvironment that suppresses the immune system.
3. Physical barriers: Dense stroma, vascular structures and tumor cell mass impede T-cell access.
4. Response durability and resistance: Tumor antigen loss and T-cell exhaustion are common.

✅ The Path Opened by TIL Therapies

Durable responses have been achieved with TIL-based treatments in advanced melanoma. Lifileucel, the first TIL product approved by the FDA in 2022, is a pioneer in this field.

📌 CAR T-Cell Trials in Solid Tumors

Targets such as mesothelin, GD2, HER2, MUC1, EGFRvIII, CEA and Claudin18.2 are being investigated. However, no CAR T-cell product has received FDA approval to date. Satricabtagene autoleucel (satri-cel) may initiate this paradigm shift in advanced gastric cancer.

And Now: Have CAR T Cells Succeeded in Solid Tumors for the First Time?

Presented at ASCO 2025 and published in The Lancet, CT041-ST-01 showed that satri-cel provided a significant progression-free survival advantage over physician's choice of treatment in patients with advanced CLDN18.2+ gastric or gastroesophageal junction cancer.

Approximately 30–60% of gastric cancers are CLDN18.2 positive. The study reported a rate of 58%. This is the first study in history to demonstrate the superiority of CAR T cells in solid tumors in a randomized controlled trial.

CT041-ST-01 Study Summary:

• Target population: Patients with advanced CLDN18.2+ gastric cancer or GEJC who have received ≥2 prior lines of therapy
• Total number of patients: 156
• Groups: Satri-cel (n=104) vs physician's choice of treatment (n=52)
• Primary objective: PFS (independent committee assessment)
• Secondary objectives: OS, response rate, safety

Scientific Findings:

🎯 Median Progression-Free Survival (PFS):

• Satri-cel: 3.25 months
• Physician's choice: 1.77 months
• Risk reduction: 63% (HR: 0.37)

💪 Median Overall Survival (OS):

• Satri-cel: 7.92 months
• Physician's choice: 5.49 months
• Note: The difference becomes more pronounced after RPSFT adjustment (HR: 0.47)

✅ Objective Response Rate (ORR):

• Satri-cel: 22%
• Physician's choice: 4%

📊 Disease Control Rate (DCR):

• Satri-cel: 63%
• Physician's choice: 25%

Side Effects and Safety:

CRS occurred in 95% of patients and was mostly low grade. Although the rate of Grade ≥3 adverse events was 99%, severe neurotoxicities such as ICANS were not reported.

• Most common: Lymphocytopenia (99%), leukopenia (98%), neutropenia (93%)

A New Era in CLDN18.2 Targeting

Antibodies such as zolbetuximab had previously been used in combination with chemotherapy. Satri-cel, however, is effective on its own and can be administered over a short period.

Clinical Practice and Future Perspective

• Satri-cel may become a new standard in the 3rd line.
• Its activity even in peritoneal metastases is important.
• Responses have also been observed in patients previously treated with CLDN18.2-targeted therapy.

Conclusion

CT041-ST-01 is the first randomized study to demonstrate the validity of CAR T-cell therapy in solid tumors. Satri-cel is more than a treatment: it is a pioneer opening the door to a new oncological paradigm.