Dual-target CAR-NK therapy against CLDN18.2 and HER2 for advanced stomach/GEJ cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

The program uses an allogeneic, cord-blood-derived CAR-NK product engineered to recognize both CLDN18.2 and HER2, with CLDN18.2 as the primary anchor antigen for gastric/GEJ disease. Phase 1 follows a 3+3 dose-escalation after fludarabine/cyclophosphamide lymphodepletion and delivers three intravenous infusions on Days 0, 3, and 7 to identify dose-limiting toxicities and a recommended phase 2 dose. Phase 2 expands at the recommended dose in CLDN18.2-positive patients with prespecified subgroup analyses by HER2 status to measure preliminary antitumor activity, durability, and survival outcomes. Correlative studies will examine CAR-NK persistence and the relationship between baseline CLDN18.2/HER2 expression and clinical response.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Signed informed consent before any study-specific procedure.
* Age 18 to 75 years.
* Histologically confirmed unresectable locally advanced or metastatic gastric adenocarcinoma or gastroesophageal junction adenocarcinoma.
* Central confirmation of CLDN18.2-positive disease by immunohistochemistry, defined for this draft as membranous CLDN18.2 expression in at least 10% of tumor cells. HER2 testing is required for all subjects; HER2-positive disease is defined as IHC 3+ or IHC 2+/ISH+ using gastric/GEJ testing criteria.
* Disease progression after at least 2 prior systemic regimens for advanced disease, including a fluoropyrimidine and platinum agent unless contraindicated or not tolerated. If HER2-positive, prior HER2-directed therapy is expected unless unavailable, contraindicated, or not tolerated.
* At least 1 measurable lesion according to RECIST v1.1.
* ECOG performance status 0 or 1.
* Life expectancy of at least 12 weeks.
* Adequate hematologic, renal, hepatic, pulmonary, and cardiac function.
* Recovery of prior treatment-related toxicities to Grade 1 or baseline, except alopecia or stable endocrine replacement therapy.
* Willingness to provide archival tumor tissue or fresh biopsy material if archival tissue is inadequate for central biomarker confirmation.
* Negative pregnancy test for women of childbearing potential and agreement to use effective contraception during the protocol-defined period

Exclusion Criteria:

* Prior CLDN18.2-targeted or HER2-targeted genetically modified cell therapy (CAR-T, CAR-NK, TCR-T, or similar).
* Active or untreated central nervous system metastases or leptomeningeal disease.
* Active uncontrolled infection, including uncontrolled HBV, HCV, or HIV viremia.
* Active autoimmune disease requiring systemic immunosuppression.
* Clinically significant uncontrolled cardiovascular disease, including recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or severe heart failure.
* Active gastrointestinal perforation, uncontrolled upper GI bleeding, clinically significant bowel obstruction, or unstable gastric ulcer.
* History of solid-organ transplantation or prior allogeneic hematopoietic stem-cell transplantation with active graft-versus-host disease.
* Requirement for systemic corticosteroids above physiologic replacement (for example, \>10 mg/day prednisone equivalent) within 7 days before lymphodepletion.
* Pregnancy or breastfeeding.
* Another active malignancy requiring systemic therapy, except for adequately treated non-melanoma skin cancer, carcinoma in situ, or other protocol-allowed low-risk malignancies.
* Any medical, psychiatric, or social condition that, in the investigator's judgment, would make study participation unsafe or would interfere with interpretation of study results.

Where it's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: shan S Lu, Phd
• Email: Seni-Lu@beijing-biotech.com
• Phone: +86 13076790030

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.