Small Cell Lung Cancer Extensive StagePhase 1NCT05680922
DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer
A Phase 1 study testing LB2102 in people with Small Cell Lung Cancer Extensive Stage and Large Cell Neuroendocrine Carcinoma of the Lung, run by Legend Biotech USA Inc at 4 sites in United States.
Trial summary
This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Small Cell Lung Cancer Extensive Stage, Large Cell Neuroendocrine Carcinoma of the Lung
- What is being tested?
- LB2102
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 4 sitesUnited States
- Study dates
- 26 Jul 2023to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Be at least 18 years of age and willing and able to provide a written informed consent
- Have histologically/cytologically confirmed unresectable small cell lung carcinoma (SCLC), large cell neuroendocrine lung carcinoma (LCNEC), combined SCLC, or combined LCNEC as per WHO 2021 criteria
- Subjects who have at least one prior line of standard treatment, and have progressed after or have had an insufficient response, and for whom standard treatment is intolerable, unlikely to confer significant clinical benefit, is no longer effective, or the subject declines further standard treatment
- Have available formalin-fixed, paraffin-embedded tumor specimen in a tissue block or unstained serial slides accompanied by an associated pathology report prior to enrollment. Archival or fresh biopsy tissue is required
- Presence of ≥ 1 radiologically measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
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- Life expectancy of at least 4 months
- Have adequate organ function
- Women of childbearing potential must have a negative pregnancy test at screening using a highly sensitive serum pregnancy test (β-human chorionic gonadotropin [β-hCG])
- All subjects must agree to practice a highly effective method of contraception (failure rate of <1% per year when used consistently and correctly) from the time of signing the informed consent form (ICF) to 1 year after receiving a LB2102 infusion
- Women and men must agree not to donate eggs (ova, oocytes) or sperm, respectively, until at least 1 year after receiving a LB2102 infusion
Who cannot join
- Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product
- Prior treatment with DLL3-targeted therapy
- Prior history of checkpoint inhibitor associated pneumonitis
- Clinically significant ascites, pleural or peritoneal effusions
- Known status of acquired or inherited immunodeficiency without the ability of medical control or normalization.
- Known leptomeningeal metastases
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- Active or symptomatic brain metastasis. Subjects with treated brain metastasis are allowed provided definitive therapy was completed at least 2 weeks prior to enrollment with at least documented stable disease and the subject is off supraphysiologic doses of steroid for at least 7 days. Additional requirements are met per protocol.
- Active autoimmune disease receiving immunomodulatory treatments (e.g., cyclosporine or high dose systemic steroids) prior to screening as follows:
- Within 2 weeks or 5 half-lives, whichever is longer
- Those with steroid replacement at physiologic doses and inhaled steroids recently or currently are not excluded.
- Impaired cardiac function or clinically significant cardiac disease not controlled by medications including:
- Unstable angina or myocardial infraction within 6 months prior to apheresis.
- History of cardiomyopathy with left ventricular ejection fraction (LVEF)<45% as assessed by ECHO and MUGA scan.
- Previous or concurrent malignancy, excluding certain exceptions.
- Serious and /or uncontrolled medical condition that, in the Investigator's judgment, would cause unacceptable safety risk, interfere with study procedures or results, or compromise compliance with the protocol, such as:
- Active, uncontrolled, viral bacterial or systemic fungal infections.
- Requirement if supplemental oxygen to maintain oxygen saturation.
- Clinical evidence of dementia or altered mental status.
- Medically uncontrolled condition or insufficient recovery from an acute event within 6 months of screening.
- Subjects with known active infection with HIV, hepatitis B, and/or hepatitis C virus (HBV/HCV) are not eligible unless additional protocol requirements are met.
- subjects with HIV must be controlled on effective antiretroviral therapy for at least four weeks and have HIV viral load of less than 400 copies/mL prior to enrollment.
- subjects with active HBV must be on suppressive antiviral therapy prior to enrollment in the study.
- For subject with history of HBV and with serologic evidence of a resolved prior infection, the risk of HBV reactivation must be considered, and the need for anti-HBV prophylaxis must be carefully assessed prior to enrollment in the study.
- Subjects with untreated HCV infection may be eligible if the HCV is stable, the subject is not at risk for hepatic decompensation and the investigational cancer treatment is not expected to exacerbate the HCV infection.
- Contraindications or life-threatening allergies, hypersensitivity, or intolerance to LB2102 excipients, such as dimethyl sulfoxide; or to fludarabine, cyclophosphamide, or tocilizumab
- Ongoing toxicity of organ functions from previous anticancer therapy that has not resolved to Grade 1 or less, except for alopecia
- Major surgery within 4 weeks prior to apheresis, or planned within 4 weeks after LB2102 administration
- Pregnant or breast-feeding
- Plans to become pregnant or breastfeed, or father a child within 1 year after receiving a LB2102 infusion
- Previous history of allogeneic hematopoietic (HSCT), organ transplant.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
University of Kentucky - Markey Cancer Center
Lexington, Kentucky, 40536
Memorial Sloan Kettering Cancer Center
New York, New York, 10017
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A First in Human Dose Escalation and Cohort Expansion Study of DLL3-directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer
This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.
Read the detailed description
This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer. The study comprises a dose-escalation component (Part A) and a cohort expansion component (Part B). Up to 41 subjects will be treated in this study. Part A will enroll and treat up to 24 subjects and Part B will be conducted after the recommended dose for expansion (RDE) has been identified in Part A and enroll up to 17 subjects. Both parts of this trial will include a Screening Period, a Pretreatment Period, a Treatment Period, a Follow-Up Period, and a Post-Progression Follow-Up Period.
- Being tested
- LB2102
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LB2102Biological
DLL3 directed autologous Chimeric Antigen Receptor T-cells
| Study group | Role | What they receive |
|---|---|---|
| Experimental LB2102 | Experimental | DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T) Receives: Biological: LB2102 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE)
Multiple doses will be tested to establish a recommended dose
Measured: 28 days
To further characterize the safety and tolerability of LB2102 with the RDE identified in the dose-escalation and determine the recommended Phase 2 dose (RP2D)
Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study
Measured: 90 days
Secondary outcomes (3)
To evaluate the preliminary efficacy of LB2102
Measured by Response Evaluation Criteria In Solid Tumors (RECIST)
Measured: Through study completion, a minimum of 2 years
To characterize the pharmacokinetics of LB2102 in blood
CAR-positive T cell counts in cells/microliter (μL) blood
Measured: Through study completion, a minimum of 2 years
To evaluate the immunogenicity of LB2102
Number of subjects with presence of anti-LB2102 antibodies
Measured: Through study completion, a minimum of 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jan 2023
- Study start26 Jul 2023
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Small Cell Lung Cancer Extensive StageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 41 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Legend Biotech USA Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05680922
- Sponsor's protocol ID
- LB2102-1001
- Status last verified
- Mar 2026
- First submitted
- 21 Dec 2022
- Last updated
- 24 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Williams CM, Arnold SM, Villano JL, Alonso ENA, Brainson CF, Schwarzenberger PO, Vahora S, Qasrawi A, Munker R, Evers BM, Hao Z. Safety and efficacy of DLL3 CAR-T cells armored with dnTGFBR2 in a subject with recurrent small-cell lung cancer: case report. Front Oncol. 2026 Jul 7;16:1885732. doi: 10.3389/fonc.2026.1885732. eCollection 2026.
PubMed 42482749Ouyang W, Xu Z, Guan S, Hu Y, Gou X, Liu Z, Guo W, Huang Y, Zhang L, Zhang X, Li T, Yang B. Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer. Int J Biol Sci. 2025 Jan 20;21(3):1322-1341. doi: 10.7150/ijbs.105973. eCollection 2025.
PubMed 39897044
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A First in Human Dose Escalation and Cohort Expansion Study of DLL3-directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT05680922
- Acronym / sponsor ID
- LB2102-1001
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 41 participants (estimated)
- Lead sponsor
- Legend Biotech USA IncIndustry (pharma, biotech, devices)
- Study start
- 26 Jul 2023 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 11 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.
Detailed description
This is a phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells in subjects with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer. The study comprises a dose-escalation component (Part A) and a cohort expansion component (Part B). Up to 41 subjects will be treated in this study. Part A will enroll and treat up to 24 subjects and Part B will be conducted after the recommended dose for expansion (RDE) has been identified in Part A and enroll up to 17 subjects. Both parts of this trial will include a Screening Period, a Pretreatment Period, a Treatment Period, a Follow-Up Period, and a Post-Progression Follow-Up Period.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Experimental LB2102 | Experimental | Biological: LB2102DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Be at least 18 years of age and willing and able to provide a written informed consent
- Have histologically/cytologically confirmed unresectable small cell lung carcinoma (SCLC), large cell neuroendocrine lung carcinoma (LCNEC), combined SCLC, or combined LCNEC as per WHO 2021 criteria
- Subjects who have at least one prior line of standard treatment, and have progressed after or have had an insufficient response, and for whom standard treatment is intolerable, unlikely to confer significant clinical benefit, is no longer effective, or the subject declines further standard treatment
- Have available formalin-fixed, paraffin-embedded tumor specimen in a tissue block or unstained serial slides accompanied by an associated pathology report prior to enrollment. Archival or fresh biopsy tissue is required
- Presence of ≥ 1 radiologically measurable lesion per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1
Key exclusion criteria (30 listed)
- Prior treatment with cellular immunotherapy (e.g., CAR-T) or gene therapy product
- Prior treatment with DLL3-targeted therapy
- Prior history of checkpoint inhibitor associated pneumonitis
- Clinically significant ascites, pleural or peritoneal effusions
- Known status of acquired or inherited immunodeficiency without the ability of medical control or normalization.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LB2102DLL3 directed autologous Chimeric Antigen Receptor T-cells | Biological | Experimental LB2102 |
Primary outcome
To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE)
Time frame: 28 days
Multiple doses will be tested to establish a recommended dose
To further characterize the safety and tolerability of LB2102 with the RDE identified in the dose-escalation and determine the recommended Phase 2 dose (RP2D)
Time frame: 90 days
Treatment of additional patients at the recommended dose as identified in the initial dose escalation part of the study
3 secondary outcomes
To evaluate the preliminary efficacy of LB2102
Time frame: Through study completion, a minimum of 2 years
To characterize the pharmacokinetics of LB2102 in blood
Time frame: Through study completion, a minimum of 2 years
To evaluate the immunogenicity of LB2102
Time frame: Through study completion, a minimum of 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2026.
- Derived from this study: PubMed 42482749Williams CM, Arnold SM, Villano JL, Alonso ENA, Brainson CF, Schwarzenberger PO, Vahora S, Qasrawi A, Munker R, Evers BM, Hao Z. Safety and efficacy of DLL3 CAR-T cells armored with dnTGFBR2 in a subject with recurrent small-cell lung cancer: case report. Front Oncol. 2026 Jul 7;16:1885732. doi: 10.3389/fonc.2026.1885732. eCollection 2026.
- Derived from this study: PubMed 39897044Ouyang W, Xu Z, Guan S, Hu Y, Gou X, Liu Z, Guo W, Huang Y, Zhang L, Zhang X, Li T, Yang B. Advancement Opportunities and Endeavor of Innovative Targeted Therapies for Small Cell Lung Cancer. Int J Biol Sci. 2025 Jan 20;21(3):1322-1341. doi: 10.7150/ijbs.105973. eCollection 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing LB2102 in people with Small Cell Lung Cancer Extensive Stage and Large Cell Neuroendocrine Carcinoma of the Lung, run by Legend Biotech USA Inc at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 24 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To characterize the safety and tolerability of LB2102 and determine recommended dose for expansion (RDE) (time frame: 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05680922, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Mar 2026.