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Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC
Sponsor: Beijing Biotech
Summary
This is a two-part, biomarker-guided Phase 1/2 study evaluating the safety, feasibility, and preliminary anti-tumor activity of off-the-shelf dual-target CAR-NK cells in participants with advanced or metastatic NSCLC whose tumors co-express at least two of the following antigens: Mesothelin (MSLN), EGFR, and HER2/ERBB2. Participants will receive lymphodepleting chemotherapy followed by infusion of the CAR-NK product matched to their tumor antigen profile. A data-driven interim assessment will be used to select the most suitable construct for expansion.
Official title: A Phase 1/2, Open-label, Biomarker-guided Study of Dual-target Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Targeting Mesothelin (MSLN) With EGFR or HER2/ERBB2, or EGFR With HER2/ERBB2, in Participants With Advanced/Metastatic Non-small Cell Lung Cancer (NSCLC)
Key Details
Gender
All
Age Range
18 Years - 75 Years
Study Type
INTERVENTIONAL
Enrollment
48
Start Date
2026-02-02
Completion Date
2028-02-17
Last Updated
2026-03-12
Healthy Volunteers
No
Interventions
Dual-target CAR-NK cells
Allogeneic cord-blood-derived NK cells engineered to express a dual-target CAR (tandem OR-gate) and IL-15 for enhanced persistence; includes an inducible safety switch (e.g., iCasp9). Infused intravenously on Day 0 (with optional repeat infusion on Day 7 in expansion, per protocol).
Lymphodepleting chemotherapy
Fludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion
Supportive Care
Premedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm)
Locations (1)
Peking University Shenzhen Hospital
Shenzhen, Guangdong, China