CClinicalTrials.gg
RecruitingNCT07744256Updated Aug 4, 2026

Adaptive Phase 1/2 Study of Dual-Target CAR-NK Cells in Relapsed/Refractory Small Cell Lung Cancer (SCLC)

A Phase 1/2 interventional study of EB-DART-NK01 and Lymphodepleting chemotherapy in Small Cell Lung Cancer (SCLC), Relapsed/Refractory SCLC and Extensive-stage SCLC, sponsored by Beijing Biotech. Recruiting at 1 site in China. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2026-08-04.

Sponsored by Beijing Biotech · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
60
Allocation
Non-randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

This example 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).

Read the detailed description

Rationale: SCLC is characterized by rapid progression, early relapse after platinum-based therapy, and antigen heterogeneity. DLL3, CD56 (NCAM1), and GD2 are frequently evaluated SCLC-associated surface targets. Dual-target CAR designs may reduce antigen-escape risk compared with single-target approaches.

Investigational products: Three off-the-shelf allogeneic CAR-NK cell products are evaluated. Each product is manufactured from healthy-donor NK cells and engineered to express a dual-target CAR plus a safety switch (e.g., inducible caspase-9) and a persistence support element (e.g., IL-15 support). The exact construct features can be adapted to the sponsor's platform.

Study schema: (1) Screening and biomarker assessment, including tumor antigen profiling for DLL3, CD56, and GD2 by immunohistochemistry (IHC) or validated equivalent assay. (2) Phase 1 dose escalation in up to three parallel arms (one arm per dual-target construct) using a modified 3+3 design to determine MTD and/or RP2D. (3) Interim construct selection based on a composite of safety (DLT rate), manufacturability/feasibility, in vivo expansion/persistence, and preliminary efficacy. (4) Phase 2 expansion cohort treated with the selected construct at RP2D to further characterize safety and estimate antitumor activity.

Conditioning and dosing: Participants receive lymphodepleting chemotherapy (e.g., fludarabine and cyclophosphamide) followed by CAR-NK infusion(s). Because NK-cell persistence can be limited, repeat dosing within a cycle is permitted (e.g., Day 0, Day 7, Day 14), and a second cycle may be allowed in responders without prohibitive toxicity.

Safety monitoring: Participants are monitored for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), infusion reactions, cytopenias, infections, and other adverse events. An independent safety monitoring committee reviews cumulative safety at each dose level and prior to construct selection.

Follow-up: Clinical follow-up continues for 24 months for efficacy and late toxicity. Long-term follow-up for gene-modified cell products (up to 15 years) may be conducted per local regulatory requirements to monitor delayed adverse events

02

Conditions studied

  • Small Cell Lung Cancer (SCLC)
  • Relapsed/Refractory SCLC
  • Extensive-stage SCLC

Keywords

  • CAR-NK
  • Dual-target
  • Adoptive cell therapy
  • Immunotherapy
  • Solid tumor
  • Small cell lung cancer
  • DLL3
  • CD56 (NCAM1)
  • GD2
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • 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 criteria

Exclusion Criteria:

  • 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.
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
60 participants (estimated)

Study arms

  • Experimental
    DLL3/CD56 Dual-Target CAR-NK

    Allogeneic dual-target CAR-NK cells targeting DLL3 and CD56 (NCAM1) following lymphodepleting chemotherapy.

    Biological: EB-DART-NK01 · Drug: Lymphodepleting chemotherapy

  • Experimental
    DLL3/GD2 Dual-Target CAR-NK

    Allogeneic dual-target CAR-NK cells targeting DLL3 and GD2 following lymphodepleting chemotherapy.

    Biological: EB-DART-NK01 · Drug: Lymphodepleting chemotherapy

  • Experimental
    CD56/GD2 Dual-Target CAR-NK

    Allogeneic dual-target CAR-NK cells targeting CD56 (NCAM1) and GD2 following lymphodepleting chemotherapy.

    Biological: EB-DART-NK01 · Drug: Lymphodepleting chemotherapy

Interventions

  • BiologicalEB-DART-NK01

    Allogeneic dual-target CAR-NK cells engineered to enhance tumor recognition and cytotoxicity against heterogeneous solid tumors.

  • DrugLymphodepleting chemotherapy

    An alkylating chemotherapy agent used as part of lymphodepleting conditioning prior to CAR-NK cell infusion to enhance cell expansion, persistence, and anti-tumor activity.

05

What researchers measure

Primary outcomes

  1. Incidence of dose-limiting toxicities

    Time frame: 28 Days

  2. maximum tolerated dose (MTD)

    maximum tolerated dose (MTD) of the drug

    Time frame: 12 months

Secondary outcomes

  1. Objective response rate

    Time frame: 12 months

  2. Disease control rate

    Time frame: 12 months

06

Study locations

1 of 1 sites recruiting
  • Peking University Shenzhen Hospital
    Shenzhen, Guangdong 518036, China
    Recruiting
07

Registry details

Key details

Study ID
NCT07744256
Lead sponsor
Beijing Biotech
Responsible party
Sponsor
First posted
Aug 4, 2026
Start date
Mar 2, 2026
Primary completion
Feb 14, 2027 (estimated)
Completion
Mar 17, 2028 (estimated)
Last update
Aug 4, 2026

Study contacts

shan S Lu, Phd
Contact
Seni-Lu@beijing-biotech.com
+86 13076790030

Oversight

Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

Contact study team

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Start the discussion