Dual-target CAR-NK therapy against CLDN18.2 and HER2 for advanced stomach/GEJ cancer
A Phase 1/2, Open-label, Multicenter Study of Allogeneic Dual-target CLDN18.2/HER2 (ERBB2) CAR-NK Cells After Fludarabine/Cyclophosphamide Lymphodepletion in
This trial will test an off-the-shelf, cord-blood-derived CAR-NK cell therapy that targets CLDN18.2 and HER2 in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have progressed after at least two prior treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Beijing Biotech Industry-sponsored |
| Drugs / interventions | CAR-T, prednisone, cyclophosphamide, fludarabine |
| Locations | 1 site (Shenzhen, Guangdong) |
| Trial ID | NCT07551362 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults aged 18–75 with histologically confirmed unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma that is centrally confirmed CLDN18.2-positive (≥10% membranous IHC), who have progressed after at least two prior systemic regimens, have ECOG 0–1, measurable disease, and adequate organ function.
Not a fit: Patients whose tumors are CLDN18.2-negative, who have poor performance status, insufficient organ function, or contraindications to lymphodepletion or prior required therapies are unlikely to benefit or be eligible.
Why it matters
Potential benefit: If successful, this approach could offer a new targeted cell-therapy option that produces tumor responses and longer disease control for patients with CLDN18.2-positive gastric or GEJ cancer, including those with heterogeneous HER2 expression.
How similar studies have performed: Prior CLDN18.2- and HER2-targeted cell-therapy programs, largely using CAR-T, have reported promising signals, but an allogeneic dual-target CAR-NK approach is relatively novel and less well characterized clinically.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Shenzhen, Guangdong
- 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
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.