Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC
Recruiting · NCT07467863 · Interventional (participants receive a specific treatment)
View the official record on ClinicalTrials.gov →Interventions studied
What this trial is about
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.
Who can take part
Age range
18 Years to 75 Years
Sex
All (male and female)
Healthy volunteers
No - a diagnosis or condition is required
Phase
Phase 1, Phase 2
Study type
Interventional (participants receive a specific treatment)
Inclusion criteria
- Histologically or cytologically confirmed NSCLC that is unresectable Stage IIIB/IIIC or Stage IV, with radiographic progression on or after standard-of-care therapy (including platinum-based chemotherapy and immune checkpoint inhibitor when appropriate).
- At least one measurable lesion per RECIST v1.1.
- Archival tumor tissue available (or willingness to undergo a fresh biopsy) for antigen testing.
- Tumor co-expression of at least two of the following antigens at screening: MSLN, EGFR, HER2/ERBB2.
- Example thresholds: IHC ≥2+ in ≥50% of tumor cells for each required antigen (or an equivalent RNA expression threshold).
- ECOG performance status 0-1.
- Adequate organ function (hematologic, hepatic, renal) as defined by protocol laboratory limits.
- Life expectancy ≥12 weeks.
- Negative pregnancy test for individuals of childbearing potential; agreement to use effective contraception for the study-defined period.
- Ability to understand and willingness to sign written informed consent.
Exclusion criteria
- Active, uncontrolled central nervous system (CNS) metastases. Participants with previously treated/stable CNS disease may be eligible if clinically stable and off high-dose corticosteroids.
- Prior gene-modified cellular therapy (e.g., CAR-T, CAR-NK, TCR-T) within 3 months, or any prior therapy that in the investigator's judgment increases risk of severe toxicity.
- History of severe cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS) with prior therapies.
- Clinically significant interstitial lung disease or pneumonitis requiring systemic steroids, or uncontrolled pulmonary comorbidity that would confound toxicity monitoring.
Where it is running
1 location listed.
- Peking University Shenzhen Hospital - Shenzhen, Guangdong, China