ClinicalTrials.gov record NCT07480213

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

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Jul 27, 2026

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

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 1/2A study that combines safety and dose-finding (phase 1) with a first look at whether the treatment has an effect (phase 2).
Age18 years old to 75 years old
SexAll
LocationChina
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This is an open-label, adaptive Phase 1/2 study testing off-the-shelf dual-target CAR‑NK cell products in adults with relapsed or refractory small cell lung cancer. Three dual-target constructs (combinations of DLL3, CD56/NCAM1, and GD2) enter parallel dose-escalation arms; an interim assessment will select one construct for expansion at the recommended Phase 2 dose. Treatment includes lymphodepleting chemotherapy followed by CAR‑NK infusions with clinical follow-up for at least 24 months and possible long-term follow-up per regulations.

What it is studying. The study is testing safety, feasibility, in‑body expansion/persistence, and preliminary antitumor activity of allogeneic dual-target CAR‑NK cells directed against DLL3, CD56 (NCAM1), and/or GD2, and will select one construct for further study.

What the researchers hope to learn. To identify dose-limiting toxicities and a recommended Phase 2 dose; to select the most feasible dual-target CAR‑NK construct based on safety, manufacturability, and early activity; to measure preliminary anti-tumor activity (response rates) and estimate survival outcomes.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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).

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Lymphodepleting chemotherapy
Biological
  • EB-DART-NK01 (DLL3/CD56 CAR-NK cells)

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

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

  • 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.

Study description and what participation involves

The study's detailed description, as published on ClinicalTrials.gov.

Show the detailed description from the registry

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.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Screening includes medical history, scans, lab tests, and tumor antigen testing (IHC or equivalent) using archival or fresh tumor tissue—a fresh biopsy may be required if archival tissue is not available. Participants receive lymphodepleting chemotherapy (fludarabine + cyclophosphamide) followed by one or more infusions of allogeneic dual-target CAR-NK cells; repeat doses within a cycle (for example Day 0, Day 7, Day 14) and a second cycle may be allowed in some responders. Safety monitoring is frequent and focuses on cytokine release syndrome, immune-related neurotoxicity, infusion reactions, cytopenias, and infections; visits include exams, scans, and blood tests. Clinical follow-up continues for 24 months, and long-term follow-up for gene-modified products may be conducted up to 15 years per local regulatory requirements.

How the study is structured. Participants undergo tumor antigen testing, then one of three parallel dose‑escalation arms using a modified 3+3 design. After lymphodepleting chemotherapy, participants receive CAR‑NK cell infusion(s); repeat doses within a cycle and an additional cycle for some responders are permitted. An interim review will choose the most suitable construct to move into an expansion cohort at the recommended Phase 2 dose. Safety monitoring includes checks for cytokine release syndrome, neurologic events, infections, and blood count changes; follow-up continues for at least 24 months with possible long-term monitoring for gene‑modified cells.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The registry lists this study under Small Cell Lung Cancer (SCLC); Relapsed/Refractory SCLC; SCLC, Extensive Stage. Does it apply to my diagnosis?
  • This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
  • The listed sites are in China. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

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Important dates

Study start
Feb 2, 2026
Primary completion
Feb 14, 2027 (estimated)
Study completion
Apr 17, 2028 (estimated)
Target enrollment
60 participants (estimated)
Last updated on registry
Mar 18, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
Beijing Biotech

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (1)

Terms used on this page · explanations by MedicalUpdates.ai

open-label
No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
relapsed or refractory
A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
dose escalation
Groups of participants receive increasing doses of a treatment, one group after another, to find a dose that can be given safely.
cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
recommended Phase 2 dose
The dose chosen at the end of a phase 1 study for testing in later studies, based on safety and other measurements.
contraindicated
A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
ECOG performance status
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
ANC
The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
x ULN
The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
Life expectancy
Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
Prior treatment
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
CAR-T
A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
investigational
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
hematopoietic stem cell transplant
A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
corticosteroid
Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
relapse
A condition that improved with treatment and has since returned or worsened.
sponsor
The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
biomarker
Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
Phase 1
An early-stage study, usually small, mainly to check safety, side effects and how much of a treatment can be given. Whether it works is not the main question yet.
MTD
The highest dose found in a dose-escalation study that can be given without too many dose-limiting side effects.
DLT
A side effect, defined in advance, that is severe enough to limit how far the dose can be raised in a dose-escalation study. How many such events stop escalation is set by the study's rules.
Phase 2
A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
cytokine release syndrome
A reaction in which the immune system releases a large amount of signalling proteins at once, causing fever and sometimes low blood pressure or breathing problems. It can occur after some immune therapies, such as CAR-T cells or bispecific antibodies.
immune effector cell-associated neurotoxicity syndrome
Nervous-system side effects, such as confusion or difficulty speaking, that can occur after some immune therapies. Usually temporary, but monitored closely.
adverse events
Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
Follow-up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
Long-term follow-up
Observation that continues for years after the study treatment, often required for gene and cell therapies.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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