Adaptive Phase 1/2 Study of Dual-Target CAR-NK Cells in Relapsed/Refractory Small Cell Lung Cancer (SCLC)
A Phase 1/2 Adaptive Dose-Escalation and Expansion Study of Dual-Targeting Chimeric Antigen Receptor Natural Killer (CAR-NK) Cells Directed Against DLL3, CD56 (NCAM1), and/or GD2 in Adults With Relapsed/Refractory Small Cell Lung Cancer
Beijing Biotech
60 participants
Feb 2, 2026
INTERVENTIONAL
Summary
This study is an open-label, multi-center, adaptive Phase 1/2 trial evaluating the safety, feasibility, and preliminary antitumor activity of allogeneic dual-target CAR-NK cell products in adults with relapsed or refractory small cell lung cancer (SCLC). Three candidate dual-target constructs (DLL3/CD56, DLL3/GD2, and CD56/GD2) will be assessed during dose escalation; a pre-specified interim assessment will select the most suitable construct to proceed into an expansion cohort at the recommended Phase 2 dose (RP2D).
Eligibility
Inclusion Criteria8
- Age 18 to 75 years at the time of consent.
- Histologically or cytologically confirmed small cell lung cancer (SCLC) that is metastatic, extensive-stage, or unresectable, and relapsed or refractory after at least 1 prior systemic regimen (must include a platinum-based regimen unless contraindicated).
- At least one measurable lesion per RECIST v1.1.
- ECOG performance status 0 to 1.
- Adequate organ function (hematologic, renal, hepatic, and cardiac) as defined in the protocol (examples: ANC \>= 1.0 x10\^9/L, platelets \>= 75 x10\^9/L, creatinine clearance \>= 50 mL/min, AST/ALT \<= 3 x ULN, total bilirubin \<= 1.5 x ULN).
- Life expectancy \>= 12 weeks.
- Tumor tissue available (archival or fresh) for antigen profiling (DLL3, CD56/NCAM1, GD2).
- Negative pregnancy test for persons of childbearing potential; agreement to use effective contraception for the protocol-defined duration.
Exclusion Criteria9
- Active or uncontrolled CNS metastases or leptomeningeal disease (treated/stable CNS metastases may be allowed per protocol).
- Prior treatment with CAR-T, CAR-NK, or other gene-modified cellular therapy within 6 months (or any prior therapy directed against the investigational target antigens if it would confound safety/efficacy assessment).
- Allogeneic hematopoietic stem cell transplant within 6 months or active graft-versus-host disease.
- Active uncontrolled infection, including uncontrolled HIV, active hepatitis B or C with viremia, or active tuberculosis.
- Clinically significant cardiovascular disease (e.g., recent myocardial infarction within 6 months, uncontrolled arrhythmia, LVEF \< 45%).
- Active autoimmune disease requiring systemic immunosuppression; chronic systemic corticosteroid use \> 10 mg/day prednisone equivalent (unless for physiologic replacement).
- Concurrent malignancy requiring active treatment (exceptions may apply for certain non-melanoma skin cancers or in situ cancers).
- Pregnant or breastfeeding.
- Any condition that, in the investigator's opinion, would make participation unsafe or interfere with compliance.
Interventions
EB-DART-NK01 (DLL3/CD56 CAR-NK cells)
(fludarabine + cyclophosphamide)
Locations(1)
View Full Details on ClinicalTrials.gov
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NCT07480213