Dual-target CAR-NK Cells for NSCLC That Co-express MSLN and 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

Participants with advanced or metastatic NSCLC whose tumors express at least two of MSLN, EGFR, or HER2 will receive lymphodepleting chemotherapy followed by a dual-target CAR-NK cell infusion matched to their tumor profile. The study uses a two-part design: a dose-escalation Part A to identify a recommended Phase 2 dose, and a Part B expansion at that dose with adaptive prioritization of the most promising construct. Exploratory aims include CAR-NK persistence, immune responses, cytokine changes, and correlations between antigen density and outcomes. The trial is conducted with an interim, data-driven assessment to refine the optimal construct for expansion.

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.
* Active autoimmune disease requiring systemic immunosuppression (physiologic steroid replacement permitted).
* Active uncontrolled infection, including uncontrolled HIV, active hepatitis B, or active hepatitis C infection.
* Significant cardiovascular disease (e.g., recent myocardial infarction, unstable angina, uncontrolled arrhythmia, or LVEF below institutional lower limit).
* Pregnant or breastfeeding.
* Concurrent anti-cancer therapy (chemotherapy, targeted therapy, immunotherapy) within protocol-defined washout periods.
* Any condition that, in the investigator's opinion, would interfere with participant safety or compliance

Where it's running

• 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

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Patient-specific MRD liquid biopsy for resected NSCLC

  This study tests a personalized MRD blood and bronchial washing test after surgery to see if it can signal recurrence earlier in people with resected NSCLC.

  Recruiting Yonsei University · Yongin-si, Gyeonggi-do and 2 other locations · NCT07921888

• Osimertinib Plus SRS/SRT for EGFR-Mutant NSCLC with Symptomatic Brain Metastases

  This study tests whether adding targeted brain radiotherapy to osimertinib helps control brain metastases in adults with EGFR-mutant NSCLC and neurological symptoms.

  Recruiting Phase 2 Cho Ray Hospital · Ho Chi Minh City · NCT07911449

• Dato-DXd in solid tumors (Urothelial Cancer and KRAS-mutant NSCLC) in two sub-studies

  This study tests Datopotamab Deruxtecan (Dato-DXd) alone or with other cancer drugs in people with urothelial cancer or KRAS-mutant non-small cell lung cancer.

  Recruiting Phase 1/2 Daiichi Sankyo · Taichung · NCT07890714

• SI-B036 safety test in advanced and metastatic solid tumors

  This early-phase study checks whether SI-B036 is safe and tolerable in adults with advanced or metastatic solid cancers who have had prior therapy.

  Recruiting at 4 sites Phase 1 SystImmune Inc. · New Haven, Connecticut and 6 other locations · NCT07857616

• Postoperative EGFR-TKI Therapy for EGFR-mutant NSCLC Following Surgery

  This registry tests whether giving an EGFR-TKI after surgery helps adults with EGFR-mutant, high-risk early-stage NSCLC.

  Recruiting Tongji Hospital · Wuhan, Hubei · NCT07837739

• HS-20093 with Adebrelimab vs HS-20093 alone in advanced non-squamous NSCLC

  This study tests whether adding adebrelimab to HS-20093 helps patients with advanced non-squamous NSCLC who have already had treatment.

  Recruiting Phase 2 Hansoh BioMedical R&D Company · Wuhan, Hubei · NCT07824882

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.