NCT07467863

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

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)

• Status: Recruiting
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 48 (estimated)
• Sponsor: Beijing Biotech · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

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

Conditions

• Non-Small Cell Lung Cancer
• Advanced/Metastatic NSCLC

Interventions

Type	Name	Description
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)

Timeline

• Start date: 2026-02-02
• Primary completion: 2027-02-14
• Completion: 2028-02-17
• First posted: 2026-03-12
• Last updated: 2026-03-12

Locations

1 site across 1 country: China