Dual-Target CAR-NK Cells Directed Against MSLN, EGFR, or HER2 in Advanced NSCLC (DUO-NK-NSCLC)

March 8, 2026 updated by: Beijing Biotech

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study includes Part A (dose escalation) and Part B (dose expansion). In Part A, participants are assigned to one of three dual-target CAR-NK constructs based on tumor antigen co-expression (IHC and/or RNA profiling): MSLN/EGFR, MSLN/HER2, or EGFR/HER2. Dose escalation within each construct follows a standard 3+3 design to identify a recommended Phase 2 dose (RP2D). In Part B, the study expands at the RP2D and may adaptively prioritize the construct demonstrating the most favorable benefit-risk profile (e.g., acceptable safety with early signals of response). Key exploratory objectives include CAR-NK persistence, immune pharmacodynamics, cytokine profiling, and correlations between antigen density and clinical outcomes. This document is an example ClinicalTrials.gov-style registration template for planning purposes only and is not an actual registered study

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Guangdong
      • Shenzhen, Guangdong, China, 518036

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: EB-DuoNK-MSLN/EGFR
Participants with tumors co-expressing MSLN and EGFR (meeting screening thresholds) receive lymphodepletion followed by EB-DuoNK-MSLN/EGFR infusion at the assigned dose level.
Biological: 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).
Drug: Lymphodepleting chemotherapy
Fludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion
Other: Supportive Care
Premedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm)
Experimental: EB-DuoNK-MSLN/HER2
Participants with tumors co-expressing MSLN and HER2/ERBB2 receive lymphodepletion followed by EB-DuoNK-MSLN/HER2 infusion at the assigned dose level.
Biological: 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).
Drug: Lymphodepleting chemotherapy
Fludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion
Other: Supportive Care
Premedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm)
Experimental: EB-DuoNK-EGFR/HER2
Participants with tumors co-expressing EGFR and HER2/ERBB2 receive lymphodepletion followed by EB-DuoNK-EGFR/HER2 infusion at the assigned dose level.
Biological: 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).
Drug: Lymphodepleting chemotherapy
Fludarabine + Cyclophosphamide administered on Days -5, -4, and -3 prior to CAR-NK infusion
Other: Supportive Care
Premedication and management per institutional guidelines (e.g., acetaminophen/antihistamine pre-infusion; tocilizumab and corticosteroids per CRS/ICANS management algorithm)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Objective response rate (ORR)
Time Frame: 6 months
6 months
Incidence of dose-limiting toxicities (DLTs)
Time Frame: 28 Days
28 Days

Secondary Outcome Measures

Outcome Measure
Time Frame
Overall survival (OS)
Time Frame: 24 months
24 months
Duration of response (DOR) per RECIST v1.1.
Time Frame: 12 months
12 months
Progression-free survival (PFS).
Time Frame: 12 months
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Beijing Biotech

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 2, 2026

Primary Completion (Estimated)

February 14, 2027

Study Completion (Estimated)

February 17, 2028

Study Registration Dates

First Submitted

February 14, 2026

First Submitted That Met QC Criteria

March 8, 2026

First Posted (Actual)

March 12, 2026

Study Record Updates

Last Update Posted (Actual)

March 12, 2026

Last Update Submitted That Met QC Criteria

March 8, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EB-CARNK-NSCLC-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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