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

NCT07641023 | Recruiting Phase 1 DMC

• 1 other identifier: EB-CARNK-NSCLC-013
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-Small Cell Lung Cancer; Advanced/Metastatic

Keywords

CAR-NK; Dual-target; Bispecific; Adoptive cell therapy; Solid tumor; Immunotherapy; Biomarker-guided; Mesothelin; EGFR; HER2; Dose escalation

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicities (DLTs)

  28 days

• Recommended Phase 2 dose (RP2D)

  28 days

• Objective response rate (ORR) per RECIST v1.1

  6 months

Secondary Outcomes (3)

• Duration of response

  12 months

• Disease control rate

  6 months

• Progression-free survival

  12 months

Study Arms (3)

EB-DuoNK-MSLN/EGFR

EXPERIMENTAL

Participants with tumors co-expressing MSLN and EGFR (meeting screening thresholds) receive lymphodepletion followed by EB-DuoNK-MSLN/EGFR infusion at the assigned dose leve

Biological: Dual-target CAR-NK cells; Drug: Lymphodepleting chemotherapy; Other: Supportive care

EB-DuoNK-MSLN/HER2

EXPERIMENTAL

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; Drug: Lymphodepleting chemotherapy; Other: Supportive care

EB-DuoNK-EGFR/HER2

EXPERIMENTAL

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; Drug: Lymphodepleting chemotherapy; Other: Supportive care

Interventions

Dual-target CAR-NK cells BIOLOGICAL

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

EB-DuoNK-EGFR/HER2; EB-DuoNK-MSLN/EGFR; EB-DuoNK-MSLN/HER2

Supportive care OTHER

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

EB-DuoNK-EGFR/HER2; EB-DuoNK-MSLN/EGFR; EB-DuoNK-MSLN/HER2

Lymphodepleting chemotherapy DRUG

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

EB-DuoNK-EGFR/HER2; EB-DuoNK-MSLN/EGFR; EB-DuoNK-MSLN/HER2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Beijing Biotech: lead

Study Sites (1)

Peking University Shenzhen Hospital

Shenzhen, Guangdong, 518036, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

Palliative Care

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Central Study Contacts

shan S Lu, Phd

CONTACT

+86 13076790030; Seni-Lu@beijing-biotech.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-label due to early-phase safety monitoring and individualized product assignment
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Participants are assigned to a construct based on tumor antigen co-expression. Each construct undergoes dose escalation (3+3) to determine RP2D, followed by expansion; an interim assessment may select one construct for larger expansion.

Study Record Dates

• First Submitted: June 6, 2026
• First Posted: June 11, 2026
• Study Start: March 2, 2026
• Primary Completion (Estimated): March 14, 2027
• Study Completion (Estimated): June 17, 2028
• Last Updated: June 11, 2026

Record last verified: 2026-06

Locations

CN (1)