DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer

NCT05680922 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: LB2102-1001
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

Small Cell Lung Cancer Extensive Stage; Large Cell Neuroendocrine Carcinoma of the Lung

Outcome Measures

Primary Outcomes (2)

• 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

  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

  90 days

Secondary Outcomes (3)

• To evaluate the preliminary efficacy of LB2102

  Through study completion, a minimum of 2 years

• To characterize the pharmacokinetics of LB2102 in blood

  Through study completion, a minimum of 2 years

• To evaluate the immunogenicity of LB2102

  Through study completion, a minimum of 2 years

Study Arms (1)

Experimental LB2102

EXPERIMENTAL

DLL3-Directed Chimeric Antigen Receptor T-cells (CAR T)

Biological: LB2102

Interventions

LB2102 BIOLOGICAL

DLL3 directed autologous Chimeric Antigen Receptor T-cells

Experimental LB2102

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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:

Sponsors & Collaborators

• Legend Biotech USA Inc: lead

Study Sites (4)

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Kentucky - Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10017, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 11, 2023
• Study Start: July 26, 2023
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: March 24, 2026

Record last verified: 2026-03

Locations

US (4)