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Dual-Target CAR-NK Cells Targeting MSLN, EGFR, or HER2 in Advanced NSCLC

ConditionsNon-Small Cell Lung CancerAdvanced/Metastatic
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorBeijing Biotech

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • Dual-target CAR-NK cells

    Biological/Vaccine

    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 . Infused intravenously on Day 1

  • Lymphodepleting chemotherapy

    Drug

    Fludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion

  • Supportive care

    Other intervention

    Premedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm).

Treatment groups

60 Participants
are divided into 3 treatment groups
Group A: EB-DuoNK-MSLN/EGFRExperimental treatment 3 interventions
Group B: EB-DuoNK-MSLN/HER2Experimental treatment 3 interventions
Group C: EB-DuoNK-EGFR/HER2Experimental treatment 3 interventions

Trial outcomes

Primary outcomes

1

Incidence of dose-limiting toxicities (DLTs)

Time frame
28 days
2

Recommended Phase 2 dose (RP2D)

Time frame
28 days
3

Objective response rate (ORR) per RECIST v1.1

Time frame
6 months

Secondary outcomes

1

Duration of response

Time frame
12 months
2

Disease control rate

Time frame
6 months
3

Progression-free survival

Time frame
12 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Beijing Biotech

Lead sponsor

Source ClinicalTrials.gov
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