Off-the-shelf dual-target CAR-NK cell therapy for advanced non-small cell lung cancer targeting MSLN with EGFR or HER2

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

This two-part Phase 1/2 program gives lymphodepleting chemotherapy followed by infusion of one of three off-the-shelf dual-target CAR-NK products selected according to the tumor's antigen profile (MSLN/EGFR, MSLN/HER2, or EGFR/HER2). Part A uses a 3+3 dose-escalation design within each construct to find a recommended Phase 2 dose, and Part B expands at that dose with adaptive prioritization of the construct showing the best early benefit-risk profile. Tumor antigen status is determined by IHC and/or RNA profiling, and a data-driven interim assessment may select the construct to advance. Exploratory objectives include CAR-NK persistence, immune pharmacodynamics, cytokine profiling, and correlations between antigen density and clinical outcomes.

Why it matters

Who can join: the full rules

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's running

• Peking University Shenzhen Hospital
  Shenzhen, Guangdong, China Recruiting

Study contacts

• Study coordinator: Seni 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.