Actively Recruiting
A Phase 1/2 Study of Allogeneic Dual-target CLDN18.2/HER2 CAR-NK Cells After Lymphodepletion in Advanced Gastric and Gastroesophageal Junction Adenocarcinoma
Led by Beijing Biotech · Updated on 2026-04-24
36
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are evaluating a new cell therapy combining allogeneic CAR-NK cells targeting both CLDN18.2 and HER2 (ERBB2) in adults with unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have previously undergone standard treatments. This phase 1/2 study aims to find the best dose and assess early signs of antitumor activity while exploring how tumor markers relate to treatment outcomes. The approach addresses the variability in cancer cell targets by combining two specific antigens relevant to this disease. In the phase 1 part, participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide from days -5 to -3, followed by three intravenous infusions of the CAR-NK cells on days 0, 3, and 7. The study uses a 3+3 dose-escalation design to identify dose-limiting toxicities and the maximum tolerated dose. In phase 2, patients receive the recommended dose on the same schedule, focusing on CLDN18.2-positive cancers, with HER2 status evaluated for subgroup analyses. Participants will be closely monitored through safety evaluations and tumor response assessments over several months, including tracking objective response rates, progression-free survival, and overall survival. The study also measures how the CAR-NK cells expand and persist in the body. Biomarker studies will help understand the link between antigen expression and clinical outcomes. The total study duration includes follow-ups up to 24 months to evaluate treatment effects and safety profiles.
CONDITIONS
Brief Title
Dual-target CLDN18.2/HER2 CAR-NK Cells for Advanced Gastric/GEJ Cancer
Who Can Participate
Eligibility Criteria
You may qualify if you...
- 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 with at least 10% tumor cell expression.
- HER2 testing completed; HER2-positive defined as IHC 3+ or IHC 2+/ISH+.
- Disease progression after at least 2 prior systemic regimens including fluoropyrimidine and platinum unless contraindicated.
- Prior HER2-directed therapy expected if HER2-positive unless contraindicated or not tolerated.
- At least 1 measurable lesion per 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 from prior treatment toxicities to Grade 1 or baseline except alopecia or stable endocrine therapy.
- Willing to provide archival or fresh tumor tissue for biomarker confirmation.
- Negative pregnancy test and agreement to use effective contraception if applicable.
You will not qualify if you...
- Prior CLDN18.2- or HER2-targeted genetically modified cell therapy.
- Active or untreated central nervous system metastases or leptomeningeal disease.
- Active uncontrolled infections including HBV, HCV, or HIV viremia.
- Active autoimmune disease requiring systemic immunosuppression.
- Significant uncontrolled cardiovascular disease.
- Active gastrointestinal perforation, uncontrolled bleeding, bowel obstruction, or unstable gastric ulcer.
- History of solid-organ transplant or allogeneic stem-cell transplant with active graft-versus-host disease.
- Systemic corticosteroids above physiologic replacement within 7 days before lymphodepletion.
- Pregnancy or breastfeeding.
- Another active malignancy requiring systemic therapy except certain low-risk cancers.
- Any condition making study participation unsafe or interfering with results as judged by investigator.
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - 3 days
Participants receive lymphodepleting chemotherapy with fludarabine and cyclophosphamide before cell therapy.
3 daily visits (in-person)
Duration - 7 days
Participants receive three infusions of dual-target CLDN18.2/HER2 CAR-NK cells after lymphodepletion.
3 infusions on Days 0, 3, and 7 (in-person)
Duration - Up to 24 months
Participants are monitored for safety, response, and survival after treatment.
Multiple visits over follow-up period
Trial Site Locations
Total: 1 location
1
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China, 518036
Actively Recruiting
Research Team
S
shan S Lu, Phd
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
2
Similar Trials
Frequently Asked Questions
Have more questions? Get in touch with our team for quick support
Not the Right Trial for You?
Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.
Already have an account? Log in here